COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders

April 8, 2024 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Booster Effects With Autoimmune Treatments in Patients With Poor Response to Initial COVID-19 Vaccine (ACV01)

This is a randomized, multi-site, adaptive, open-label clinical trial comparing the immune response to different additional doses of COVID-19 vaccine in participants with autoimmune disease requiring IS medications. All study participants will have negative serologic or suboptimal responses (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL) or a low immune response (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result >200 U/ml and ≤2500 U/mL) to their previous doses of COVID-19 vaccine.

The study will focus on 5 autoimmune diseases in adults:

Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis (RA)
Multiple Sclerosis (MS)
Systemic Sclerosis (SSc), and
Pemphigus.

This study will focus on 4 autoimmune diseases in pediatric participants:

Systemic Lupus Erythematosus (SLE)
Juvenile Idiopathic Arthritis (JIA)
Pediatric-Onset Multiple Sclerosis (POMS)
Juvenile Dermatomyositis (JDM)

Study Overview

Detailed Description

Adult Population:

Stage 1 of this trial will enroll up to a maximum of 900 adult study participants (up to 60 participants per arm).

Participants will be assigned to one of 3 cohorts based on their IS regimens:

Cohort A: Receipt of MMF or MPA
Cohort B: Receipt of MTX
Cohort C: Receipt of any BCDT within the past 18 months.

Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same COVID-19 vaccine as their original vaccine series. The trial initially enrolled participants who were vaccinated with the Pfizer-BioNTech COVID-19 Vaccine, the Moderna COVID-19 Vaccine, and the Janssen COVID-19 Vaccine. Update: Arms to receive an additional homologous vaccine dose after an initial Janssen COVID 19 Vaccine were closed to enrollment after the CDC updated its recommendations to express a clinical preference for individuals to receive an mRNA COVID-19 vaccine over the Janssen COVID-19 vaccine. All Adult Stage 1 treatment arms were closed to enrollment on 15 August 2022.

Participants in Cohorts A and B will be randomized into 2 IS medication treatment plans as follows:

Participants continue to take their cohort-defining IS medications without alterations in schedule and dosing.
Participants withhold their cohort-defining IS medications before and after the additional homologous vaccine dose per protocol instructions.

A participant will be enrolled in the study for a maximum of approximately 13 months.

Stage 2 of this trial will include up to a maximum of 960 adult study participants (up to 80per arm) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after previous COVID-19 vaccine administration (at least 3 doses of mRNA vaccine(s) or 2 doses of the Janssen COVID-19 Vaccine). Participants will be eligible to receive a dose of an alternative COVID-19 vaccine.

Participants may have received their previous COVID-19 vaccine prior to enrollment in the study ("newly recruited participant"), or they may have received their previous COVID-19 vaccine as a study participant and then (re-) enter into Stage 2 ("rollover participant"). Participants can also roll over into Stage 2 via two pathways:

Stage 1 participant rolls over to Stage 2
Stage 2 participant rolls over to a different Stage 2 treatment arm

Participants will be allocated to 1 of 3 cohorts based on their IS regimens:

Cohort D: Receipt of MMF or MPA
Cohort E: Receipt of MTX
Cohort F: Receipt of any BCDT within the past 18 months.

Treatment Arms: Participants in Cohorts D, E, and F will receive a dose of an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Originally, participants who previously received 3 total doses of a single mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer- BioNTech COVID-19 Vaccine) received their choice of either the Janssen vector-based COVID-19 vaccine or the other mRNA COVID-19 vaccine, and participants who previously received 2 doses of the Janssen vector based COVID-19 vaccine received the Moderna COVID-19 Vaccine.

Update: Beginning with v4.0 of the protocol, this trial will not utilize the Janssen vector-based COVID-19 vaccine. Participants who previously received 3 total doses of a single mRNA vaccine will receive their choice of an alternative mRNA COVID-19 vaccine or the Sanofi-GSK protein based COVID-19 vaccine. Participants who previously received 4 or more doses of a single mRNA vaccine or 3 or more doses of a mixture mRNA vaccines (Moderna COVID-19 Vaccine AND Pfizer-BioNTech COVID-19 Vaccine, in any order or combination) will receive the Sanofi-GSK protein-based COVID-19 vaccine.

Participants in Cohorts D and E will withhold their cohort-defining IS medications before and after the alternative vaccine dose per protocol instructions. Participants in Cohort F who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications before and after the alternative vaccine dose per protocol instructions.

Visits to assess endpoints will occur at Baseline (Week 0), Week 4 ± 1 week, Week 12 ± 2 weeks, Week 24 ± 2 weeks, Week 36 ± 2 weeks, and Week 48 ± 2 weeks. A participant who is newly recruited to the study for entry into Stage 2 may be on study for up to a maximum of 13 months. A participant who enters Stage 2 after a serologic negative, suboptimal, or low immune response to their Stage 1 vaccine dose may be on study for up to a maximum of 26 months. Rollover participants will discontinue follow-up as part of Stage 1 upon rollover into Stage 2. A participant who rolls over to a different Stage 2 treatment arm 2 after a serologic negative, suboptimal, or low immune response to another Stage 2 vaccine dose may be on study for up to a maximum of 38 months.

Pediatric Population:

Stage 1 in the pediatric portion of this trial will enroll up to a maximum of 800 participants (2-17 years of age) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after receiving an initial COVID-19 vaccine regimen (up to 80participants per arm). Vaccines will be included in this protocol as they receive EUA or approval by FDA for a given age group. Pediatric participants will have 1 of 4 autoimmune diseases: pediatric SLE, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), or pediatriconset multiple sclerosis (POMS). Participants will be assigned to 1 of 3 cohorts based on their IS regimens:

Cohort A: Receipt of MMF or MPA
Cohort B: Receipt of MTX
Cohort C: Receipt of any BCDT within the past 18 months.

Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same vaccine as their original vaccine series. Based on FDA EUA status, pediatric participants were initially eligible to receive the Pfizer-BioNTech COVID-19 Vaccine only.

Participants in Cohorts A and B will be randomized into 2 IS medication treatment plans as follows):

Participants continue to take their cohort-defining IS medications without alterations in schedule and dosing.
Participants withhold their cohort-defining IS medications before and after the additional homologous vaccine dose per protocol instructions.

A participant will be enrolled in the study for a maximum of approximately 13 months.

Stage 2 of the pediatric portion of this trial will include up to a maximum of 480 pediatric study participants (up to 80 per arm) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after previous COVID-19 vaccine administration (an age-appropriate EUA-authorized or FDA-approved initial COVID-19 vaccine regimen plus 1 additional dose of the same vaccine). All participants (2-17 years of age) who previously received doses of the Pfizer-BioNTech COVID-19 Vaccine are eligible to receive an age-appropriate dose of the Moderna COVID-19 Vaccine. Participants 12 through 17 years of age who previously received doses of the Moderna COVID-19 vaccine are eligible to receive an age-appropriate dose of the Pfizer-BioNTech COVID-19 Vaccine. Participants will be eligible to receive a dose of an alternative COVID-19 vaccine. Participants may have received their previous COVID-19 vaccine as a study participant and then enter into Stage 2 ("rollover participant"), or they may have received their previous COVID-19 vaccine prior to enrollment in the study ("newly recruited participant").

Participants will be allocated to 1 of 3 cohorts based on their IS regimens:

Cohort D: Receipt of MMF or MPA (± other rheumatic disease medications, including biologics)
o Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) will be placed in this cohort.
Cohort E: Receipt of MTX (± other rheumatic disease medications, including biologics)
o Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort.
Cohort F: Receipt of B cell depletion therapy within the past 18 months (± other rheumatic disease medications) o Participants taking B cell depletion medications, regardless of whether they are also taking MMF or MTX, will be placed in this cohort.

Treatment Arms: Participants in Cohorts D, E, and F will receive a dose of an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Participants who previously received age-appropriate doses of a single mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer-BioNTech COVID-19 Vaccine, as noted above) will receive the other mRNA COVID-19 vaccine.

Beginning with v7.0 of the protocol all vaccines used are bivalent versions replacing original monovalent versions.

Participants in Cohorts D and E will withhold their cohort-defining IS medications before and after the alternative vaccine dose per protocol instructions (see Section 7.1.1 Protocol-mandated Medications).

Participants in Cohort F who are taking MMF, MPA, or MTX in addition to B cell depletion therapies (BCDTs) will withhold these medications before and after the alternative vaccine dose per protocol instruction.

A participant who enters Stage 2 after a serologic negative, suboptimal, or low immune response to their Stage 1 vaccine dose may be on study for up to a maximum of 26 months. Rollover participants will discontinue follow-up as part of Stage 1 upon rollover into Stage 2. A participant who is newly recruited to the study for entry into Stage 2 may be on study for up to a maximum of 13 months.

Adaptive Design

An adaptive design will be employed such that cohorts and arms defined by additional vaccine doses and IS treatment plans may be added or modified based on emerging data from existing and new FDA Emergency Use Authorization (EUA) or approvals of COVID-19 vaccines:

New cohorts may be defined based on changes in the medication groups if it becomes obvious that certain medications are highly associated with suboptimal or low immune serologic response to initial COVID-19 vaccine regimen.
Cohorts may limit or expand the autoimmune diseases that are eligible to be included in the clinical trial and may include expansion cohorts of underrepresented diseases.
New cohorts may include participants whose antibody response falls to suboptimal or low immune levels over time.
Based upon timing of the FDA EUA authorization for children of each of the COVID-19 vaccines used in this trial, the age range of the inclusion criteria may be expanded.
Allocation or randomization to treatment with new COVID-19 vaccines may be incorporated into the design when the products become available.
Identification of additional strategies to enhance vaccine responsiveness in autoimmune diseases, including a temporary switch of immunomodulatory medications.

Study Type

Interventional

Enrollment (Actual)

257

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- California
  - Los Angeles, California, United States, 90095
    - UCLA Medical Center: Division of Rheumatology
- Connecticut
  - New Haven, Connecticut, United States, 06519
    - Yale University School of Medicine: Rheumatology, Allergy & Immunology
- Georgia
  - Atlanta, Georgia, United States, 30322
    - The Emory Clinic: Division of Rheumatology
- Indiana
  - Indianapolis, Indiana, United States, 46202
    - Indiana University Medical Center, Riley Hospital for Children
- Massachusetts
  - Boston, Massachusetts, United States, 02115
    - Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology
  - Boston, Massachusetts, United States, 02114
    - Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases
  - Boston, Massachusetts, United States, 02115
    - Boston Children's Hospital: Department of Pediatrics, Rheumatology Program
- Michigan
  - Ann Arbor, Michigan, United States, 48109
    - University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology
- Missouri
  - Saint Louis, Missouri, United States, 63110
    - Washington University School of Medicine in St. Louis: Division of Rheumatology
- New York
  - Manhasset, New York, United States, 11030
    - Feinstein Institute for Medical Research
  - Manhasset, New York, United States, 11030
    - Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
  - New York, New York, United States, 10021
    - Hospital for Special Surgery
  - New York, New York, United States, 10016
    - New York University Langone Medical Center: Department of Medicine, Division of Rheumatology
  - New York, New York, United States, 10032
    - Columbia University Irving Medical Center: Department of Neurology, Multiple Sclerosis Center
  - Rochester, New York, United States, 14642
    - University of Rochester Medical Center
  - Stony Brook, New York, United States, 11794-8111
    - Stony Brook University Hospital
- North Carolina
  - Chapel Hill, North Carolina, United States, 27599
    - University of North Carolina Children's Hospital
  - Durham, North Carolina, United States, 27710
    - Duke University Medical Center: Division of Rheumatology and Immunology
- Ohio
  - Cleveland, Ohio, United States, 44195
    - Cleveland Clinic
  - Columbus, Ohio, United States, 43205
    - Nationwide Children's Hopspital
- Oklahoma
  - Oklahoma City, Oklahoma, United States, 73104
    - Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
  - Oklahoma City, Oklahoma, United States, 73104
    - Oklahoma Children's Hospital-Pediatrics Specialties Clinic
- Pennsylvania
  - Philadelphia, Pennsylvania, United States, 19104
    - University of Pennsylvania Perelman Center for Advanced Medicine
  - Philadelphia, Pennsylvania, United States, 19104
    - Temple Health: Rheumatology
- South Carolina
  - Charleston, South Carolina, United States, 29425
    - Medical University of South Carolina, Nexus Research Center
  - Charleston, South Carolina, United States, 29425
    - Medical University of South Carolina, Shawn Jenkins Children's Hospital
- Texas
  - Dallas, Texas, United States, 75325
    - UT Southwestern (Peds)
  - Houston, Texas, United States, 77030
    - University of Texas Houston Medical School: Division of Rheumatology and Clinical Immunogenetics
- Washington
  - Seattle, Washington, United States, 98101
    - Benaroya Research Institute at Virginia Mason: Internal Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Description

General Adult Inclusion Criteria:

1. Willing and able to sign informed consent 2. Documented full COVID-19 vaccination (CDC card or documentation in medical records) that was completed at least 4 weeks prior and no more than 52 weeks prior to the Stage 1 Screening visit, or if participating in Stage 2, no more than 48 weeks prior to the Stage 2 Screening visit.

General Exclusion Criteria 2. History of severe allergic reaction to the initial COVID-19 vaccine regimen, to any component of any of the COVID-19 vaccines, or to polyethylene glycol (PEG).

3. New diagnosis of malignancy that will require chemotherapy or immunotherapy, or ongoing treatment for a malignancy with chemotherapy or immunotherapy.

4. Active disease (per the Investigator's decision) resulting in inability to hold the IS therapy in the MMF/MPA or MTX arms of the study.

a. The potential impact of temporarily holding medication for participants with a recent mild disease flare within 4 weeks should be carefully considered.

5. Active disease during the Screening period resulting in:

An increase/addition of any IS medications, or
A suggestion of MS relapse per the investigator. 6. Recent or current SARS-CoV-2 infection defined as:

Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening).
Positive result on a molecular COVID-19 test at Screening. 8. Inflammatory myocarditis/pericarditis within 6 weeks of any COVID-19 vaccine doses.
9. Participants with active, ongoing chronic infections. Note: Participants are permitted to be on chronic prophylactic antimicrobial therapy. Adults with evidence of HIV, Hepatitis B indicated by surface antigen, and Hepatitis C indicated by anti-hepatitis C antibody positivity will be excluded. If an adult is negative for Hepatitis C viral load at Screening, he/she will be eligible to participate.
10. Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy. Note: Pediatric participants on IVIG therapeutically may enter the study provided they have sufficiently quiet disease that they can withhold their IVIG from 8 weeks prior to the Screening visit through 4 weeks after vaccination.
11. Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 30 days of Screening.
12. Participants who have received any live vaccines within 2 months of the anticipated study vaccine dose or who will have need of a live vaccine at any time during the study.
13. Currently pregnant or breastfeeding (For pediatric participants postmenarchal females must have a negative urine pregnancy test at Screening).
15. Hemoglobin (Hgb) <8.0 g/dL (80 g/L) 16. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
17. Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of Screening.
18. Concurrent treatment with cyclophosphamide. Adult participants taking cladribine, alemtuzumab, or mitoxantrone will also be excluded.
19. Participants currently on any type of dialysis, or who have received a solid organ transplant.
20. Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
21. Taking both MMF/MPA and MTX. 22. Receiving other investigational BCDT as part of a clinical trial within 18 months of Screening, unless drug assignment is known and the participant received an anti-CD20 or CD19 drug.
23. Participants with active systemic infections who have received systemic antimicrobials within the 14 days prior to Screening.
Adult General Criteria
Inclusion Criteria:
1. Individuals 18 years of age or older that meet classification criteria for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), multiple sclerosis (MS), or pemphigus
2. Participants must meet the 2019 ACR/EULAR or 2012 SLICC classification criteria for SLE, the 2010 ACR/EULAR classification criteria for RA, the 2013 EULAR/ACR classification criteria for SSc, the 2017 McDonald criteria for MS, and the international consensus criteria for pemphigus.

If a participant has been diagnosed with more than one autoimmune disease, the participant will be assessed based on the disease that is selected for study entry 6. Must be currently taking one of the following IS medications with or without additional disease-related medications: MMF (minimum of 1000 mg per day)/MPA (minimum of 720 mg per day), MTX (minimum of 7.5mg per week), or B cell depleting agents within the past 18 months (such as rituximab, ocrelizumab, ofatumumab).

If taking MMF/MPA or MTX, the participant must have initiated therapy at least 8 weeks prior to randomization and be taking the same medications (regardless of dose) as at the time of the initial COVID-19 vaccine regimen. Note: Participants who withheld their IS medications around their initial vaccinations are eligible to participate.
If enrolling in the BCDT cohort, the participant must have received an anti-CD20 or an anti-CD19 BCDT in the past 18 months.
7. No changes in background IS medications, including MMF/MPA or MTX, in the 4 weeks prior to Screening, excluding the following:

HCQ,
Intraarticular steroids,
The addition of prednisone at ≤10mg per day or prednisone at any dose when given for ≤3 days, and
Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or COPD, are permitted.
Adult General Exclusion Criterion 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
14. Adult female participants who are planning a pregnancy during the course of the trial.
Adult Stage 1-Specific Inclusion Criterion 5. Negative or suboptimal serologic response to initial COVID-19 vaccine regimen, defined as an Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL, at Screening visit.

Initial COVID-19 vaccine regimen is defined as either:

i.2 doses of the Pfizer-BioNTech COVID-19 Vaccine ii. 2 doses of the Moderna COVID-19 Vaccine

Adult Stage 1-Specific Exclusion Criterion 7. Receipt of a COVID-19 vaccine booster prior to Screening with the Moderna COVID-19 Vaccine, Pfizer-BioNTech COVID-19 Vaccine, or Janssen COVID-19 Vaccine.

Adult Stage 2 (Newly Recruited)-Specific Inclusion Criteria 2. History of severe allergic reaction to the COVID-19 vaccine, or to any component of the COVID-19 vaccine, that is to be administered in Stage 2, including polysorbate for participants receiving the Sanofi-GSK COVID-19 Vaccine, or to PEG.

5. Negative or suboptimal serologic response to a previous COVID 19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows:

3 doses of the Pfizer-BioNTech COVID-19 Vaccine
3 doses of the Moderna COVID-19 Vaccine
2 doses of the Janssen COVID-19 Vaccine
4 or more doses of a single mRNA vaccine (Pfizer-BioNTech COVID-19 Vaccine OR Moderna COVID-19 Vaccine)
3 or more doses of a mixture of mRNA vaccines (Pfizer-BioNTech COVID-19 Vaccine OR Moderna COVID-19 Vaccine)

Adult Stage 2 (Newly Recruited)-Specific Exclusion Criteria:

7. Receipt of a mixture of Janssen COVID-19 vaccines and mRNA COVID-19 vaccines (in any order or combination) prior to Stage 2 Screening.

Adult Stage 2 (Rollover)-Specific Inclusion Criteria:

Individuals who were previously enrolled in Adult Stage 1 or Adult Stage 2 will have met some inclusion and exclusion criteria at that time. Only a subset of the criteria for (re-)entering Adult Stage 2 will be assessed in rollover participants at the time of screening for Stage 2.

Individuals who meet all of the following criteria are eligible to (re )enter Adult Stage 2:

2. History of severe allergic reaction to the COVID-19 vaccine, or to any component of the COVID-19 vaccine, that is to be administered in Stage 2, including polysorbate for participants receiving the Sanofi-GSK COVID-19 Vaccine, or to PEG.

a. 3 doses of the Pfizer-BioNTech COVID-19 Vaccine b. 3 doses of the Moderna COVID-19 Vaccine c. 2 doses of the Janssen COVID-19 Vaccine d. 4 doses of a combination of mRNA vaccines (i.e., Pfizer-BioNTech COVID-19 Vaccine, Moderna COVID-19 Vaccine)

General Pediatric Inclusion Criteria

Individuals 2-17 years of age that meet classification criteria for SLE, JIA, POMS, or JDM. Note: Juvenile idiopathic arthritis includes the following conditions: polyarticular JIA (both RF + and -), oligoarticular persistent and oligoarticular extended JIA, psoriatic arthritis, and enthesitis related JIA.
1. Participants must meet the 2017 EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups, the International League of Associations for Rheumatology (ILAR) classification for JIA, the 2017 McDonald criteria for MS, or the Bohan and Peter criteria or the 2017 EULAR/ACR classification criteria for JDM.
2. If a participant has been diagnosed with more than one autoimmune disease, the participant will be assessed based on the disease that is selected for study entry.
Parents/guardians of all pediatric participants and participants ages 14 - 17 must be willing and able to sign informed consent. Participants ages 7-13 must be willing and able to sign assent.

5. Must be currently taking one of the following IS medications with or without additional disease-related medications: MMF (minimum of 250 mg per day)/MPA (minimum of 360 mg per day), MTX (minimum of 5 mg per week), or B cell depleting agents within the past 18 months (such as rituximab, ocrelizumab, or ofatumumab).

If taking MMF/MPA or MTX, the participant must have initiated therapy at least 8 weeks prior to randomization and be taking the same medications (regardless of dose) as at the time of the initial COVID-19 vaccine regimen. Note: Participants who withheld their IS medications around their initial vaccinations are eligible to participate.
If enrolling in the BCDT cohort, participant must have received an anti-CD20 or an anti-CD19 BCDT in the past 18 months.
6. No changes in background IS medications, including MMF/MPA or MTX, in the 8 weeks prior to Screening, excluding the following:

a. HCQ, b. Intraarticular steroids, c. The addition of prednisone at <0.15mg/kg/dose per day or prednisone at any dose when given for ≤3 days, and d. Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or COPD, are permitted

General Pediatric Exclusion Criteria 1. Inability or unwillingness of a participant to give assent or of a parent/guardian to give written informed consent, or of either to comply with study protocol.

Pediatric Stage 1-Specific Inclusion Criteria:

4. Negative or suboptimal serologic response to initial EUA-authorized or FDA-approved COVID-19 vaccine doses, defined as an Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 1 Baseline/Week 0 visit

Initial COVID-19 vaccine regimen is defined as:

i. Pfizer-BioNTech COVID-19 Vaccine (2 through 4 years of age): 3 age-appropriate doses ii. Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years of age): 2 age-appropriate doses iii. Moderna COVID-19 Vaccine (2 through 17 years of age): 2 age-appropriate doses.

Pediatric Stage 1-Specific Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for randomization/allocation as participants in the pediatric portion of the study:

7. Receipt of a COVID-19 vaccine booster prior to Screening.

Pediatric Stage 2 (Newly Recruited)-Specific Inclusion Criteria 5. Negative or suboptimal serologic response to homologous doses of COVID-19 vaccine in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows: a. Pfizer-BioNTech COVID-19 Vaccine (2 through 5 years of age): 4 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine b. Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years old): 3 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine Note: Participants who are 5 years old and previously received the Pfizer-BioNTech COVID-19 Vaccine may have received either age-appropriate regimen.

c. Moderna COVID-19 Vaccine (12 through 17 years of age): 3 full, age-appropriate doses of the Moderna COVID-19 Vaccine

Pediatric Stage 2 (Newly Recruited)-Specific Exclusion Criteria:

7. Receipt of an additional heterologous COVID-19 vaccine dose prior to Stage 2 Screening, i.e., a participant cannot have received a mixture of mRNA vaccines.

Pediatric Stage 2 (Rollover)-Specific Inclusion Criteria:

5. Negative or suboptimal serologic response to a previous COVID-19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows:

Pfizer-BioNTech COVID-19 Vaccine (2 through 5 years of age): 4 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine
Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years old): 3 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine Note: Participants who are 5 years old and previously received the Pfizer-BioNTech COVID-19 Vaccine may have received either age-appropriate regimen.
Moderna COVID-19 Vaccine (12 through 17 years of age): 3 full, age-appropriate doses of the Moderna COVID-19 Vaccine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A, Arm A1: Moderna mRNA-1273 + Continue IS (MMF or MPA) Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: Moderna mRNA-1273 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine mRNA-1273 vaccine (Moderna) Moderna COVID-19 Vaccine COVID-19 vaccine Drug: Continue IS (MMF or MPA) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication
Experimental: Cohort A, Arm A2: BNT162b2 + Continue IS (MMF or MPA) Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Drug: Continue IS (MMF or MPA) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: BNT162b2 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine Pfizer-BioNTech COVID-19 vaccine mRNA-1273 vaccine (Pfizer/BioNTech)
Experimental: Cohort A, Arm A3: Ad26.COV2.S + Continue IS (MMF or MPA) Arm closed, effective protocol version 3.0. Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Drug: Continue IS (MMF or MPA) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine
Experimental: Cohort A, Arm A4: Moderna mRNA-1273 + Withhold IS (MMF or MPA) Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.	Biological: Moderna mRNA-1273 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine mRNA-1273 vaccine (Moderna) Moderna COVID-19 Vaccine COVID-19 vaccine Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication
Experimental: Cohort A, Arm A5: BNT162b2 + Withhold IS (MMF or MPA) Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.	Biological: BNT162b2 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine Pfizer-BioNTech COVID-19 vaccine mRNA-1273 vaccine (Pfizer/BioNTech) Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication
Experimental: Cohort A, Arm A6: Ad26.COV2.S + Withhold IS (MMF or MPA) Arm closed, effective protocol version 3.0. Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction.	Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication
Experimental: Cohort B, Arm B1: Moderna mRNA-1273 + Continue IS (MTX) Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: Moderna mRNA-1273 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine mRNA-1273 vaccine (Moderna) Moderna COVID-19 Vaccine COVID-19 vaccine Drug: Continue IS (MTX) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MTX methotrexate
Experimental: Cohort B, Arm B2: BNT162b2 + Continue IS (MTX) Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: BNT162b2 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine Pfizer-BioNTech COVID-19 vaccine mRNA-1273 vaccine (Pfizer/BioNTech) Drug: Continue IS (MTX) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MTX methotrexate
Experimental: Cohort B, Arm B3: Ad26.COV2.S + Continue IS (MTX) Arm closed, effective protocol version 3.0. Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine Drug: Continue IS (MTX) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MTX methotrexate
Experimental: Cohort B, Arm B4: Moderna mRNA-1273 + Withhold IS (MTX) Adult Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.	Biological: Moderna mRNA-1273 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine mRNA-1273 vaccine (Moderna) Moderna COVID-19 Vaccine COVID-19 vaccine Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate
Experimental: Cohort B, Arm B5: BNT162b2 + Withhold IS (MTX) Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster, per protocol instruction.	Biological: BNT162b2 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine Pfizer-BioNTech COVID-19 vaccine mRNA-1273 vaccine (Pfizer/BioNTech) Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate
Experimental: Cohort B, Arm B6: Ad26.COV2.S + Withhold IS (MTX) Arm closed, effective protocol version 3.0. Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction.	Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate
Experimental: Cohort C, Arm C1: Moderna mRNA-1273 + Continue IS (B cell depletion therapy) Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: Moderna mRNA-1273 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine mRNA-1273 vaccine (Moderna) Moderna COVID-19 Vaccine COVID-19 vaccine Biological: Continue IS (B cell depletion therapy) Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb
Experimental: Cohort C, Arm C2: BNT162b2 + Continue IS (B cell depletion therapy) Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: BNT162b2 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine Pfizer-BioNTech COVID-19 vaccine mRNA-1273 vaccine (Pfizer/BioNTech) Biological: Continue IS (B cell depletion therapy) Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb
Experimental: Cohort C, Arm C3: Ad26.COV2.S + Continue IS (B cell depletion therapy) Arm closed, effective protocol version 3.0. Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine Biological: Continue IS (B cell depletion therapy) Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb
Experimental: Cohort D, Arm D1: Ad26.COV2.S + Withhold IS (MMF or MPA) Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.	Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication
Experimental: Cohort E, Arm E1: Ad26.COV2.S + Withhold IS (MTX) Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.	Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate
Experimental: Cohort F, Arm F1: Ad26.COV2.S + Withhold IS (B cell depletion therapy) Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.	Biological: Ad26.COV2.S Administration: One dose administered intramuscularly. Other Names: JNJ-78436735 Janssen COVID-19 Vaccine Drug: Withhold IS (B cell depletion therapy) Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb
Experimental: Cohort D, Arm D4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MMF or MPA) Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: Monovalent [B.1.351] CoV2 preS dTM-AS03 One dose administered intramuscularly Other Names: Sanofi-GSK COVID-19 Vaccine
Experimental: Cohort E, Arm E4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MTX) Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate Biological: Monovalent [B.1.351] CoV2 preS dTM-AS03 One dose administered intramuscularly Other Names: Sanofi-GSK COVID-19 Vaccine
Experimental: Cohort F, Arm F4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (B cell depletion therapy) Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction	Drug: Withhold IS (B cell depletion therapy) Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb Biological: Monovalent [B.1.351] CoV2 preS dTM-AS03 One dose administered intramuscularly Other Names: Sanofi-GSK COVID-19 Vaccine
Experimental: Cohort D, Arm D2: Alternative mRNA Vaccine + Withhold IS (MMF or MPA) Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of an alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.	Biological: BNT162b2 Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine Pfizer-BioNTech COVID-19 vaccine mRNA-1273 vaccine (Pfizer/BioNTech) Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort D, Arm D3: Moderna mRNA-1273 + Withhold IS (MMF or MPA) Adult participants who previously received the Janssen COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.	Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort E, Arm E2: Alternative mRNA Vaccine + Withhold IS (MTX) Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of an alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.	Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort E, Arm E3: Moderna mRNA-1273 + Withhold IS (MTX) Adult participants who previously received the Janssen COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.	Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort F, Arm F2: Alternative mRNA Vaccine + Withhold IS (B cell depletion therapy) Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.	Drug: Withhold IS (B cell depletion therapy) Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort F, Arm F3: Moderna mRNA-1273 + Withhold IS (B cell depletion therapy) Adult participants who previously received the Janssen COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.	Drug: Withhold IS (B cell depletion therapy) Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort A, Arm A1P: Moderna mRNA-1273, Bivalent + Continue IS (MMF or MPA) Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Drug: Continue IS (MMF or MPA) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort A, Arm A2P: BNT162b2, Bivalent + Continue IS (MMF or MPA) Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Drug: Continue IS (MMF or MPA) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort A, Arm A4P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA) Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort A, Arm A5P: BNT162b2, Bivalent + Withhold IS (MMF or MPA) Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort B, Arm B1P: Moderna mRNA-1273, Bivalent + Continue IS (MTX) Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Drug: Continue IS (MTX) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MTX methotrexate Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort B, Arm B2P: BNT162b2, Bivalent + Continue IS (MTX) Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Drug: Continue IS (MTX) Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing. Other Names: MTX methotrexate Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort B, Arm B4P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX) Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort B, Arm B5P: BNT162b2, Bivalent + Withhold IS (MTX) Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster, per protocol instruction.	Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort C, Arm C1P: Moderna mRNA-1273, Bivalent + Continue IS (B cell depletion therapy) Pediatric participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: Continue IS (B cell depletion therapy) Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort C, Arm C2P: BNT162b2, Bivalent + Continue IS (B cell depletion therapy) Pediatric participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.	Biological: Continue IS (B cell depletion therapy) Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort D, Arm D1P: BNT162b2, Bivalent + Withhold IS (MMF or MPA) Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort D, Arm D2P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA) Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MMF or MPA) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MMF MPA mycophenolic acid mycophenolate mofetil CellCept® immunosuppressive medication Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort E, Arm E1P: BNT162b2, Bivalent + Withhold IS (MTX) Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort E, Arm E2P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX) Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (MTX) Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions. Other Names: MTX methotrexate Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent
Experimental: Cohort F, Arm F1P: BNT162b2, Bivalent + Withhold IS (B cell depletion therapy) Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (B cell depletion therapy) Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb Biological: BNT162b2, Bivalent Administration: One dose administered intramuscularly. Other Names: SARS-CoV-2 RNA vaccine, Bivalent mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent Pfizer-BioNTech COVID-19 vaccine, Bivalent
Experimental: Cohort F, Arm F2P: Moderna mRNA-1273, Bivalent + Withhold IS (B cell depletion therapy) Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.	Drug: Withhold IS (B cell depletion therapy) Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing. Other Names: mAbs targeting CD19 or CD20 anti-BAFF mAb Biological: Moderna mRNA-1273, Bivalent Administration: One dose administered intramuscularly. Other Names: mRNA-1273 vaccine (Moderna), Bivalent Moderna COVID-19 Vaccine, Bivalent SARS-CoV-2 RNA vaccine, Bivalent COVID-19 vaccine, Bivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of adult and pediatric participants who have a protective antibody response at Week 4 Time Frame: Week 4 Status Post Receipt of COVID-19 Vaccination	Efficacy measure.	Week 4 Status Post Receipt of COVID-19 Vaccination

Secondary Outcome Measures

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Rho Federal Systems Division, Inc.

Autoimmunity Centers of Excellence

Investigators

Study Chair: Judith A. James, MD, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation
Study Chair: Meggan C. Mackay, MD, MS, Center of Autoimmune Musculoskeletal and Hematopoietic Diseases, Feinstein Institute for Medical Research
Study Chair: Dinesh Khanna, MBBS, MSc, University of Michigan Health, Michigan Medicine
Study Chair: Amit Bar-Or, MD, FRCP, Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania
Study Chair: Virginia Pascual, MD, Drukier Institute for Children's Health, Weill Cornell Medical College
Study Chair: Stacy Ardoin, MD, Nationwide Children's Hospital Rheumatology Department
Study Chair: Natasha Mckerran Ruth, MD, Medical University of South Carolina, Pediatric Rheumatology
Study Chair: Tracey Wright, MD, UT Southwestern Medical Center, Pediatric Rheumatology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Autoimmunity Centers of Excellence (ACE)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 13, 2021

Primary Completion (Actual)

June 22, 2023

Study Completion (Actual)

March 28, 2024

Study Registration Dates

First Submitted

August 6, 2021

First Submitted That Met QC Criteria

August 6, 2021

First Posted (Actual)

August 11, 2021

Study Record Updates

Last Update Posted (Actual)

April 10, 2024

Last Update Submitted That Met QC Criteria

April 8, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

DAIT ACV01
NIAID CRMS ID#: 38873 (Other Identifier: DAIT NIAID)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

IPD Sharing Time Frame

On average, within 24 months after database lock for the trial.

IPD Sharing Access Criteria

Open access.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Systemic Lupus Erythematosus (SLE)

University Hospital, Brest

Recruiting

3TR (Taxonomy, Treatment, Targets and Remission) Systemic Lupus Erythematosus Study Protocol 2 (3TR-SLE2)

Systemic Lupus Erythematosus (SLE)

France
Beijing InnoCare Pharma Tech Co., Ltd.

Recruiting

Evaluate the Efficacy and Safety of Orelabrutinib in Adult Patients With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus, SLE

China
TJ Biopharma Co., Ltd.

Terminated

A Study to Evaluate the Safety, Tolerability, and PK Profile of Single and Multiple Doses TJ202 in Patient With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE)

China
Novartis Pharmaceuticals

Active, not recruiting

Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients

Systemic Lupus Erythematosus (SLE)

Hungary, Spain, Germany, Israel, Thailand, France, Russian Federation, China, Japan, Taiwan, Korea, Republic of, Poland, Australia, Argentina, Czechia
University of Sao Paulo General Hospital
Fundação de Amparo à Pesquisa do Estado de São Paulo

Completed

Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases

Systemic Lupus Erythematosus (SLE) | Cutaneous Lupus | Juvenile SLE

Brazil
AstraZeneca

Not yet recruiting

INTERSTELLAR - International Study Evaluating Lupus Outcomes After Anifrolumab Real World Use (INTERSTELLAR)

Systemic Lupus Erythematosus (SLE)
Hangzhou Sumgen Biotech Co., Ltd.

Recruiting

SG301-SC Injection Safety Study in Subjects With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE)

China
Cartesian Therapeutics

Recruiting

Descartes-08 for Patients With Systemic Lupus Erythematosus (SLE-001)

Systemic Lupus Erythematosus (SLE)

United States
Oklahoma Medical Research Foundation
Yale University; Columbia University; NYU Langone Health; Piedmont Heart Institute...

Recruiting

Nature of Anifrolumab Impact on Vaccine-Emergent Immunity in SLE (NAIVE)

Systemic Lupus Erythematosus (SLE)

United States
Phramongkutklao College of Medicine and Hospital

Completed

Gradual Withdrawal of Low-dose Glucocorticoid in Clinically Quiescent Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus, SLE

Thailand

Clinical Trials on Moderna mRNA-1273

University of California, Los Angeles
ModernaTX, Inc.

Completed

High-Dose Moderna mRNA-1273 Booster Study for Lung Transplant Recipients

SARS-CoV-2 | Immunosuppression | Lung Transplant Recipient

United States
National Institute of Allergy and Infectious Diseases...

Completed

A Study of SARS CoV-2 Infection and Potential Transmission in Individuals Immunized With Moderna COVID-19 Vaccine (CoVPN 3006)

SARS-CoV-2 Infection

United States
University Medical Center Groningen

Active, not recruiting

Vaccination Against COVID-19 in Cancer (VOICE)

Cancer

Netherlands
Oliver Cornely, MD
European Commission; VACCELERATE

Completed

Assessing Immune Response of Different COVID-19 Vaccines in Older Adults (EU-COVAT-1)

COVID-19 | Vaccination; Infection | Vaccination Reaction

Spain, Ireland, Germany, Norway, Lithuania
National Institute of Allergy and Infectious Diseases...
PPD

Completed

COVID-19 Protection After Transplant Pilot Study (CPAT)

Kidney Transplant Recipients

United States
National Institute of Allergy and Infectious Diseases...

Completed

SARS-CoV-2 Immune Responses After COVID-19 Therapy and Subsequent Vaccine

Covid19 | SARS-CoV2 Infection

United States
Italian Group for the study of Inflammatory Bowel...

Unknown

Effectiveness and Safety of COVID-19 Vaccine in Patients With IBD Treated With Immunomodulatory or Biological Drugs (ESCAPE-IBD) (ESCAPE-IBD)

Inflammatory Bowel Diseases
Murdoch Childrens Research Institute
Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute...

Withdrawn

COVID-19 Fourth Dose Study in Australia

COVID-19

Australia
Indiana University

Terminated

Immune Responses in Oncology Patients to Novel Coronavirus Vaccines (IROC)

Cancer

United States
Regeneron Pharmaceuticals

Completed

COVID-19 Study to Assess Immunogenicity, Safety, and Tolerability of Moderna mRNA-1273 Vaccine Administered With Casirivimab+Imdevimab in Healthy Adult Volunteers

Healthy | Chronic Stable Illness

United States

Outcome Measure	Measure Description	Time Frame
Percentage of Subset Participants Who Seroconverted Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48	Efficacy measure, evaluated in subset of participants who are anti-COVID-19 antibody negative at Baseline.	Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48
Fold increase in anti-COVID-19 antibody levels at Week 4, following participant receipt of a booster dose of COVID-19 vaccine Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster), Week 4 Status Post Receipt of COVID-19 Vaccine Booster Dose	Efficacy measure, evaluated in subset of participants who are anti-COVID-19 antibody positive at Week 0 (Baseline).	Baseline (prior to receipt of COVID-19 vaccine booster), Week 4 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in anti-COVID-19 antibody response Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48	Efficacy measure.	Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48
Change in anti-SARS-CoV-2 neutralizing antibody levels Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48	Efficacy measure, employing neutralization and pseudo-neutralization assays.	Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48
Change in disease activity after receipt of additional doses of COVID-19 vaccine as measured by the Clinical Global Impression of Change (CGI-C) Time Frame: Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Dose	A measure of disease activity and efficacy. CGI-C: Clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.	Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Dose
Change in disease activity after receipt of additional doses of COVID-19 vaccine as measured by the Physician's Global Assessment Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in adult participant subset with Systemic Lupus Erythematosus (SLE) as measured by Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of SLE disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in adult participant subset with Systemic Lupus Erythematosus (SLE) as measured by Thanou modified SELENA-SLEDAI Flare Index for Systemic Lupus Erythematosus (SLE) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48	A measure of SLE disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48
Change in disease activity in adult participant subset with Rheumatoid Arthritis (RA) as measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of RA disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in adult participant subset with Systemic Sclerosis (SSc) as measured by Disease Flare Activity Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of SSc disease activity and efficacy. SSc disease flare assessments (including participant self- reported flare assessment). A flare is indicative of increased SSc-related disease activity.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in adult participant subset with Pemphigus as measured by Disease Area Index (PDAI) for Pemphigus Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of pemphigus disease activity and efficacy. The PDAI is specific cutaneous and mucosal disease activity assessment performed by the physician and is based on evaluation of lesions in well-defined anatomical locations.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in adult participant subset with Multiple Sclerosis (MS) as measured by Physician assessed relapse for MS Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of MS disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participant subset with juvenile idiopathic arthritis (JIA) as measured by JADAS10 Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of JIA disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participant subset with JIA as measured by Psoriasis Area and Severity Index (PASI) for psoriatic arthritis Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of JIA disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participant subset with pediatric-onset multiple sclerosis (POMS) as measured by SLEDAI-2K Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of MS disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participant subset with POMS as measured by childhood-onset SLE Criteria for Global Flare Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of POMS disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participant subset with juvenile dermatomyositis (JDM) as measured by Childhood Mysositis Assessment Scale Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of JDM disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participant subset with JDM as measured by JDM Disease Activity Score (DAS) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of JDM disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participant subset with Multiple Sclerosis (MS) as measured by Physician assessed relapse for MS (POMS) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of MS disease activity and efficacy.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in adult participants as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of disease activity and efficacy. The Patient-Reported Outcomes Measurement Information System (PROMIS-29) self-report assesses functioning and well-being in physical, mental and social domains of health. The PROMIS-29 consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity in pediatric participants as measured by the Pediatric Quality of Life Inventory (PedsQL) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of disease activity and efficacy. The Patient-Reported Outcomes Measurement Information System (PROMIS-29) self-report assesses functioning and well-being in physical, mental and social domains of health. The PROMIS-29 consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity as measured by the Patient Global Assessment Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of disease activity and efficacy. The patient global assessment of disease activity is measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. Change=<week status post receipt of booster vaccine> score minus baseline score. A negative score indicates an improvement in disease activity and a positive score indicates worsening.	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Change in disease activity as measured by the Patient Global Impression of Change (PGI-C) Time Frame: Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose	A measure of disease activity and efficacy. Participant's Global Impression of Change Reported on PGI-C Scale (1-7 Point Scale Ranging From 1 "Very Much Improved" to 7 "Very Much Worse").	Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose
Proportion of participants who experience any solicited Grade 1 or higher adverse events related to additional doses of the COVID-19 vaccine Time Frame: Through Day 7 post study vaccination	Safety measure status post receipt of study vaccination.	Through Day 7 post study vaccination
Proportion of participants who experience any unsolicited Grade 1 or higher adverse events related to additional doses of the COVID-19 vaccine Time Frame: Through Day 28 post study vaccination	Safety measure status post receipt of study vaccination.	Through Day 28 post study vaccination
Proportion of participants who experience any serious adverse events (SAEs) Time Frame: Up to Week 48 post study vaccination	Safety measure status post receipt of study vaccination.	Up to Week 48 post study vaccination
Proportion of participants who experience any medically attended adverse events (MAAEs) Time Frame: Up to Week 48 post study vaccination	Safety measure status post receipt of study vaccination.	Up to Week 48 post study vaccination
Proportion of participants who experience any New Onset Chronic Medical Conditions (NOCMCs) Time Frame: Up to Week 48 post study vaccination	Safety measure status post receipt of study vaccination.	Up to Week 48 post study vaccination
Proportion of participants who experience any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection Time Frame: Up to Week 48 post study vaccination	Efficacy measure.	Up to Week 48 post study vaccination