COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)

Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing and Emerging Variants

This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) >/ = 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and = 65 years of age) (however arms 16 and 17 or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (= 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID-19 for all 4 stages. The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination.

Study Overview

Detailed Description

This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) >/= 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and = 65 years of age) (however arms 16 and 17 or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (= 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID-19 for all 4 stages. This is an adaptive design and may add arms of new vaccine platforms and/or variant lineage spike vaccines as needed. The study arms will be conducted in different stages (that could overlap) depending on public health needs and the availability of study products (starting with the available mRNA vaccines). The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination. The secondary objective is to evaluate the safety of candidate SARS-CoV-2 variant vaccines, as assessed by: a) Local and systemic solicited Adverse Events for 7 days following each vaccine dose; b) Unsolicited Adverse Events from Dose 1 to 28 days following each vaccine dose; c) Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interests (AESIs), New Onset of Chronic Medical (NOCMCs) and Adverse Events (AEs) leading to withdrawal from the study from Dose 1 to 12 months after last vaccine dose.

Study Type

Interventional

Enrollment (Actual)

1270

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

    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham School of Medicine - Alabama Vaccine Research Clinic
    • California
      • San Diego, California, United States, 92103-8208
        • University of California, San Diego (UCSD) - Antiviral Research Center (AVRC)
      • San Francisco, California, United States, 94110-2859
        • Zuckerberg San Francisco General Hospital, UCSF Positive Health Program
    • District of Columbia
      • Washington, District of Columbia, United States, 20060
        • Howard University - Department of Medicine - Division of Infectious Disease
      • Washington, District of Columbia, United States, 20037-3201
        • George Washington University Medical Faculty Associates
    • Georgia
      • Atlanta, Georgia, United States, 30310
        • Morehouse School of Medicine - Clinical Research Center
      • Atlanta, Georgia, United States, 30322-1013
        • Emory University School of Medicine
      • Decatur, Georgia, United States, 30030-1705
        • The Hope Clinic of Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago College of Medicine - Division of Infectious Diseases
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals & Clinics - Department of Internal Medicine
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Clinical Translational Unit
    • Massachusetts
      • Boston, Massachusetts, United States, 02115-6110
        • Brigham and Women's Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine in St. Louis - Infectious Disease Clinical Research Unit
      • Saint Louis, Missouri, United States, 63104-1015
        • Saint Louis University Center for Vaccine Development
    • New York
      • Mineola, New York, United States, 11501
        • NYU Grossman School, NYU Langone Vaccine Center, Long Island
      • New York, New York, United States, 10016
        • NYU Langone Vaccine Center Research Clinic, Manhattan
      • Rochester, New York, United States, 14611-3201
        • University of Rochester Medical Center - Vaccine Research Unit
    • North Carolina
      • Durham, North Carolina, United States, 27703
        • Duke Vaccine and Trials Unit
    • Texas
      • Houston, Texas, United States, 77030-3411
        • Baylor College of Medicine
      • League City, Texas, United States, 77573
        • University of Texas Medical Branch
    • Washington
      • Seattle, Washington, United States, 98101
        • Kaiser Permanente Washington Health Research Institute
      • Seattle, Washington, United States, 98104
        • The University of Washington - Virology Research Clinic

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible to participate in this study:

  1. Individuals > / = 18 years of age at the time of consent. (18-49 years for stage 4).
  2. Confirmed receipt of a complete primary and booster COVID-19 vaccine series, either homologous or heterologous, with an FDA authorized/approved vaccine at least 16 weeks prior to study vaccine dose 1.
  3. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.
  4. Determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health.

Note: Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment, can be included at the discretion of the investigator.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from the study:

  1. Confirmed SARS-CoV-2 infection < 16 weeks prior to any study vaccine dose.
  2. Pregnant and breastfeeding participants.
  3. Prior administration of an investigational coronavirus vaccine at any time or SARS-CoV-2 immunoglobulin, monoclonal antibody or plasma antibody therapy in the preceding 3 months.

    Note: subjects that participated in clinical trials of products that are now FDA approved/authorized are allowed to participate.

  4. Current/planned simultaneous participation in another interventional study or receipt of any investigational study product within 28 days prior to vaccine study dose(s).
  5. A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine, polyethylene glycol (PEG), polysorbate or nanolipid particles.
  6. A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in stages 1, 2 and 4).
  7. Received or plans to receive a vaccine within 28 days prior to or after any dose of study vaccine.

    Note: Receipt of seasonal influenza vaccine is allowed at any time.

  8. Bleeding disorder diagnosed by a healthcare provider (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or bleeding difficulties with intramuscular injections or blood draws.
  9. Current or previous diagnosis of an immunocompromising condition or other immunosuppressive condition.
  10. Advanced liver or kidney diseases.
  11. Advanced (CD4 count < 200) and/or untreated HIV, untreated Hepatitis B or untreated Hepatitis C.
  12. Received oral, intramuscular or intravenous systemic immunosuppressants, or immune-modifying drugs for >14 days in total within 6 months prior to any study vaccine dose (for corticosteroids = 20 mg > / = day of prednisone equivalent).

    Note: Topical medications are allowed.

  13. Received immunoglobulin or blood-derived products, within 3 months prior any study vaccine dose.
  14. Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to any study vaccine dose.
  15. Study personnel or an immediate family member or household member of study personnel.
  16. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as > / = 38.0 degrees Celsius/100.4 degrees Fahrenheit). Participants meeting this criterion may be rescheduled within the relevant window periods.

    Note: Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator, as long as the illness is not suggestive of COVID-19.

  17. Plan to receive a COVID-19 booster vaccine outside of the study within the next 180 days. (for subjects in Stage 4 only)

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)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 01
mRNA-1273 administered through 0.2 mg/ml intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).
0.9% Sodium Chloride Injection
Experimental: Arm 02
0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
0.9% Sodium Chloride Injection
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain.
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Experimental: Arm 03
0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
0.9% Sodium Chloride Injection
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain.
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Experimental: Arm 04
0.2 mg/ml of mRNA-1273.617.2 and 0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
0.9% Sodium Chloride Injection
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.617.2 (Delta) variant SARS-CoV-2 strain.
Experimental: Arm 05
0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
0.9% Sodium Chloride Injection
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Experimental: Arm 06
0.2 mg/ml of mRNA-1273.529 and mRNA-1273 0.2 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).
0.9% Sodium Chloride Injection
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Experimental: Arm 07
500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.
Experimental: Arm 08
500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.
Experimental: Arm 09
500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Experimental: Arm 10
500 mcg/mL of BNT162b2 (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.
Experimental: Arm 11
500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.
Experimental: Arm 12
500 mcg/mL of BNT162b2 (Omicron) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Experimental: Arm 13
500 mcg/mL CoV2 preS dTM-AS03 [D614] (prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
AS03 oil-in-water emulsion adjuvant.
Is a liquid formulation made of recombinant protein placed in a formulation buffer. The antigen solution contains the spike protein sequence of the ancestral strain of SARS-CoV-2.
Experimental: Arm 14
500 mcg/mL CoV2 preS dTM-AS03 [B.1.351] (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
AS03 oil-in-water emulsion adjuvant.
Is a liquid formulation made of recombinant protein placed in a formulation buffer that contains the spike protein sequence of the B.1.351 (Beta) variant SARS-CoV-2 strain.
Experimental: Arm 15
500 mcg/mL CoV2 preS dTM-AS03 [D614 + B.1.351] (prototype + Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
AS03 oil-in-water emulsion adjuvant.
Is a liquid formulation made of recombinant protein placed in a formulation buffer contains the spike protein sequences of the ancestral and B.1.351 (Beta) variant SARS-CoV-2 strains
Experimental: Arm 16
100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.1) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in > / = 49 years) N=100
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.1 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2.
Experimental: Arm 17
100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in > / = 49 years) N=100
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.4/BA.5 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Geometric Mean Fold Rise (GMFR)
Time Frame: Day 1 through Day 366
As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.
Day 1 through Day 366
Change from baseline in Geometric Mean Titers (GMT)
Time Frame: Day 1 through Day 366
As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.
Day 1 through Day 366
Change in Geometric Mean Ratio
Time Frame: Day 1 through Day 366
As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.
Day 1 through Day 366

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events (AEs) leading to withdrawal from the study
Time Frame: Day 1 through Day 366
Day 1 through Day 366
Incidence of Adverse Events of Special Interest (AESI)
Time Frame: Day 1 through Day 366
Day 1 through Day 366
Incidence of Medically Attended Adverse Events (MAAEs)
Time Frame: Day 1 through Day 366
Day 1 through Day 366
Incidence of New Onset Chronic Medical Conditions (NOCMCs)
Time Frame: Day 1 through Day 366
Day 1 through Day 366
Incidence of Serious Adverse Events (SAE)
Time Frame: Day 1 through Day 366
Day 1 through Day 366
Incidence of Solicited Adverse Events
Time Frame: Day 1 through Day 8
Local and systemic events
Day 1 through Day 8
Incidence of Unsolicited Adverse Events
Time Frame: Day 1 through Day 29
Day 1 through Day 29

Collaborators and Investigators

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

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.

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)

March 30, 2022

Primary Completion (Actual)

November 10, 2023

Study Completion (Actual)

November 10, 2023

Study Registration Dates

First Submitted

March 17, 2022

First Submitted That Met QC Criteria

March 18, 2022

First Posted (Actual)

March 21, 2022

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

October 3, 2022

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

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