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

Completed

• Conditions: Multiple Sclerosis; Covid19

• Registration Number: NCT04834401
• Lead Sponsor: St. Barnabas Medical Center

Brief Summary

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.

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 Timeline

• Study Start: 2021-03-22
• Study First Submitted: 2021-04-02
• Study First Submitted QC: 2021-04-02
• Study First Posted: 2021-04-08
• Primary Completion: 2022-05-17
• Study Completion: 2022-05-17
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-16
• Last Update Posted: 2022-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Saint Barnabas Medical Center; 🇺🇸 Livingston, New Jersey, United States