Clinical trial NCT04834401: Effect of Disease Modifying Therapy on Antibody Response to COVID19 Vaccination in Multiple Sclerosis
Official title: Evaluating the Effect of Disease Modifying Therapy on Antibody Response to COVID19 Vaccination in People With Multiple Sclerosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Covid19
Keywords: mRNA vaccine
Ocrelizumab
Natalizumab
Dimethyl Fumarate
Diroximel Fumarate
Interferon Beta
SARS-CoV-2
Lead sponsor: St. Barnabas Medical Center
Sponsor class: OTHER
First posted: 2021-04-08
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Geometric mean titers (GMT) of anti-SARS-CoV-2 spike IgG for each treatment at 8 weeks from initial vaccination dose
timeFrame: 8 weeks
Secondary outcomes:
measure: Proportion of participants with >4 fold increase in anti-SARS-CoV-2 spike IgG between baseline and 8 weeks
timeFrame: 8 weeks
measure: Proportion of participants with >2 fold increase in anti-SARS-CoV-2 spike IgG between baseline and 8 weeks
timeFrame: 8 weeks
measure: Median time from peak to complete absence of anti-SARS-CoV-2 IgG for each treatment arm
timeFrame: 18 months
measure: Proportion of spike-specific T-cells/Total T cells
timeFrame: 36 Weeks
Other outcomes:
measure: Proportion of participants with known vaccine-related side effects
timeFrame: 8 weeks
measure: COVID-19 Infections
timeFrame: 18 months
measure: Effect of Duration of DMT use on Humoral Response to mRNA-1273
timeFrame: 8 week
Locations:
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
Study officials:
affiliation: RWJBarnabas Health
name: Matthew A Tremblay, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: