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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Covid19, Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 to 65 years inclusive Patients who have signed written informed consent. 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: Known history of SARS-CoV-2 infection Is pregnant or breastfeeding ≤6 months on current therapy (MS Participants) Participation in another investigational study Recent immunization with a non-COVID vaccine (within 4 weeks) Known or suspected allergy or history of anaphylaxis or other significant adverse reaction to the COVID-19 vaccine or its excipients Absolute lymphocyte count <0.5 x 10^9/L Concurrent Intravenous or Subcutaneous Immunoglobulin treatment (IVIG/SCIG) 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Natalizumab<br>Natalizumab (minimum of 6 doses at standard interval) | |
| Fumarates<br>Fumarates (dimethyl fumarate or diroximel fumarate) | |
| Interferon Beta 1a<br>Interferon Beta 1a (or pegylated Interferon Beta-1a) | |
| Ocrelizumab<br>Ocrelizumab (minimum of 2 full cycles of 600mg) | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ocrelizumab, mRNA vaccine, Natalizumab, Dimethyl Fumarate, Diroximel Fumarate, Interferon Beta, SARS-CoV-2