Effect of Disease Modifying Therapy on Antibody Response to COVID19 Vaccination in Multiple Sclerosis

Evaluating the Effect of Disease Modifying Therapy on Antibody Response to COVID19 Vaccination in People With Multiple Sclerosis

This observational study is intended to evaluate the effect of disease modifying therapies on antibody responses to the mRNA-1273 vaccine (Moderna) for COVID-19. We hypothesize that the use of certain disease modifying therapies, particularly ocrelizumab, will mute and/or shorten the duration of humoral response to mRNA vaccines.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Covid19

Detailed Description

COVID-19 is a potentially fatal respiratory illness, caused by the novel coronavirus, SARS-CoV-2, which developed into a pandemic claiming the lives of over 500,000 people in the United States and over 2.5 million worldwide. Antibodies against the spike glycoprotein are believed to confer immunity to SARS-CoV-2. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, which is typically treated with immunomodulating medications, referred to as disease modifying therapies (DMTs). Some DMTs resulted in a diminished capacity to develop antibodies against natural infection with SARS-CoV-2. This study is designed to evaluate and compare the effect of DMTs on antibody response to mRNA vaccines for COVID-19. Serum samples will be collected from 30 participants per treatment arm at 8 weeks, 24 weeks, 36 weeks, and 48 weeks, following vaccination with mRNA-1273. Geometric mean titers of anti-SARS-CoV-2 spike IgG will be measured to evaluate and compare peak antibody titers, as well as the duration of antibody response. The results will likely impact clinical decision-making, and guide treatment strategies for safely managing MS during the ongoing pandemic.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified from the MS Center utilizing the electronic medical record, clinic visits or telephone encounters related to COVID-19 vaccination and recruited consecutively. Patients who appear to meet eligibility criteria will be contacted by research staff and offered informed consent using the Multiple Sclerosis Comprehensive Care Center standard protocol. If possible the baseline serum sample will be collected at the initial research visit, following the informed consent process.

Description

Inclusion Criteria:

1. Men and women aged 18 to 65 years inclusive
2. Patients who have signed written informed consent.

3. Patients stable on current MS DMT for >6 months including:

   • Natalizumab (received a minimum of 6 doses per USPI)
   • Fumarates (dimethyl fumarate or diroximel fumarate)
   • Interferon Beta 1a (or pegylated Interferon Beta-1a)
   • Ocrelizumab (received a minimum of 2 full cycles per USPI)

Exclusion Criteria:

1. Known history of SARS-CoV-2 infection
2. Is pregnant or breastfeeding
3. ≤6 months on current therapy (MS Participants)
4. Participation in another investigational study
5. Recent immunization with a non-COVID vaccine (within 4 weeks)
6. Known or suspected allergy or history of anaphylaxis or other significant adverse reaction to the COVID-19 vaccine or its excipients
7. Absolute lymphocyte count <0.5 x 10^9/L
8. Concurrent Intravenous or Subcutaneous Immunoglobulin treatment (IVIG/SCIG)
9. Received systemic corticosteroids < 30 days prior to Vaccine Dose 1

Visit and Assessment Schedule:

Participants will agree to five visits during the study and serum will be collected at the following time points:

• Baseline/Screening visit
• 8 weeks after 1st dose/4 weeks after 2nd dose (+/- 1 week)
• 24 weeks (+/- 2 weeks)
• 36 weeks (+/- 4 weeks)
• 48 weeks (+/- 4 weeks)

Approximately 20ml of blood will be collected per patient per each visit.

Data Collection Plan and Patient Privacy Protection Prior to any testing under this protocol, including screening tests and assessments, candidates must also provide all authorizations required by local law (e.g., PHI authorization in North America).

The subject will not be identified by name in the CRF or in any study reports, and these reports will be used for research purposes only. Ethics committees and various government health agencies may inspect the records of this study. Every effort will be made to keep the subject's personal medical data confidential.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Natalizumab; Natalizumab (minimum of 6 doses at standard interval)
Fumarates; Fumarates (dimethyl fumarate or diroximel fumarate)
Interferon Beta 1a; Interferon Beta 1a (or pegylated Interferon Beta-1a)
Ocrelizumab; Ocrelizumab (minimum of 2 full cycles of 600mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titers (GMT) of anti-SARS-CoV-2 spike IgG for each treatment at 8 weeks from initial vaccination dose	Serum Sample	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with >4 fold increase in anti-SARS-CoV-2 spike IgG between baseline and 8 weeks	Serum sample	8 weeks
Proportion of participants with >2 fold increase in anti-SARS-CoV-2 spike IgG between baseline and 8 weeks	Serum Sample	8 weeks
Median time from peak to complete absence of anti-SARS-CoV-2 IgG for each treatment arm	Serum Sample	18 months
Proportion of spike-specific T-cells/Total T cells	Whole Blood Sample	36 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with known vaccine-related side effects	Questionnaire	8 weeks
COVID-19 Infections	Number of participants with PCR-confirmed COVID-19 infection following vaccination	18 months
Effect of Duration of DMT use on Humoral Response to mRNA-1273	Correlation between duration of DMT and GMT values for SARS-CoV-2 IgG within each treatment arm	8 week

Collaborators and Investigators

• Sponsor: St. Barnabas Medical Center
• Investigators: Principal Investigator: Matthew A Tremblay, MD, PhD, RWJBarnabas Health

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 22, 2021
• Primary Completion (ACTUAL): May 17, 2022
• Study Completion (ACTUAL): May 17, 2022

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (ACTUAL): April 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; mRNA vaccine; Natalizumab; Dimethyl Fumarate; Ocrelizumab; Diroximel Fumarate; Interferon Beta
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Multiple Sclerosis; Sclerosis; COVID-19
• Other Study ID Numbers: US-TYS-11909

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No