Clinical trial NCT05060354: COVID-19 Vaccine Response in Treated MS Patients
Official title: Immune Response to SARS-CoV2 Vaccinations in Treated MS Patients Compared to Controls
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Healthy
Keywords: Multiple Sclerosis
COVID-19
mRNA vaccine
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-09-29
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For this study, we will prospectively collect data and biospecimens from MS patients and healthy volunteers. MS patients will largely be recruited from the Brigham MS Center at Brigham and Women's Hospital (Boston MA US). Healthy volunteers will be recruited from the community surrounding BWH and through IRB-approved recruitment advertisements. The Brigham MS Center sees 2500 patients annually and is adjacent to an ongoing COVID vaccine clinic.

Brief summary: The primary goal of this study is to assess the impact of the two major disease modifying therapy (DMT) classes (B cell therapies and S1P modulators) on humoral and cell-mediated immunity to SARS- CoV-2 vaccination compared to non-MS controls. We have chosen to compare DMT-treated MS patients to non-MS controls because the pivotal vaccine studies were conducted in non-MS healthy control groups in which there is significant clinical data and validated assays for antibody responses.

Detailed description: Multiple sclerosis (MS) affects approximately 1 million persons in the United States and is the leading cause of disability in young adults. Disease modifying treatments for MS act through modulation or suppression of immune responses including B and T cell responses. Two major classes of drugs used to treat MS are 1) B cell antibodies, including Kesimpta (ofatumumab) and Ocrevus (ocrelizumab), and 2) S1P (sphingosine-1-phosphate) modulators including Gilenya (fingolimod) and Mayzent (siponimod). SARS-CoV2 is a potentially fatal novel coronavirus, which has claimed over 350,000 lives in the United States. The causative agent of COVID-19 disease, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes the angiotensin converting enzyme II (ACE2) to target cells in the lower airway.(1, 2) Symptoms of COVID-19 infection can cause pneumonia with primarily lymphocytic inflammatory infiltrates.(3) Most people (approximately 81%) experience mild upper respiratory tract infection or mild pneumonia, while approximately 15-20% of cases experience severe or critical disease characterized by dyspnea, lung infiltrates, respiratory failure and multiple organ dysfunction.(4) The case- fatality rate ranges from 0.7-5.8%. SARS-CoV2 vaccines have just been FDA approved, including the Moderna® and Pfizer-BioNTech® vaccines which contain lipid nanoparticle- formulated nucleoside-modified mRNA (messenger ribonucleic acid) that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein.(5, 6) Prior work suggests that vaccine responses may be blunted in patients treated with these two drug classes, however there is currently no controlled data on the efficacy and durability of SARS-CoV2 vaccine responses in treated MS patients. Current data is limited to uncontrolled case reports.

Robust studies are needed to inform the efficacy of SARS-CoV2 vaccines in MS patients on DMTs, which will guide infection risk management.

The primary goal of this study is to assess the impact of the two major DMT classes (B cell therapies and S1P modulators) on humoral and cell-mediated immunity to SARS- CoV-2 vaccination compared to non-MS controls. We have chosen to compare DMT-treated MS patients to non-MS controls because the pivotal vaccine studies were conducted in non-MS healthy control groups in which there is significant clinical data and validated assays for antibody responses.

The primary endpoint of this study is to compare the percentage of MS patients on immunotherapy with a positive SARS-CoV-2 Spike antibody response (positive seroconversion) compared to the percentage of controls who seroconvert at 5-6 months post vaccination.

Secondary endpoints of this study are:

* Comparison of SARS-CoV-2 Spike antibody % seroconversion and titers in MS patients on immunotherapy to titers in controls at 2-3 months and 11-12 months post vaccination.
* Comparison of T cell responses to SARS-CoV-2 spike protein in MS patients on immunotherapy to titers in controls at 5-6 months post vaccination.
* Comparison of antibody titers and T cell responses between the four groups of immunotherapies evaluated and to controls at each of the three timepoints.

Eligibility criteria: Inclusion Criteria:

For MS Patients:

1. Diagnosis of MS
2. Treatment with one of the four DMTs (Kesimpta (ofatumumab), Ocrevus (ocrelizumab), Gilenya (fingolimod), Mayzent (siponimod)) for at least 3 months prior to first SARS-CoV2 vaccine dose
3. SARS-CoV2 vaccine regimen complete within the past 2-3 or 5-6 months (either Moderna® or Pfizer-BioNTech® mRNA vaccines)
4. Age 18-65, inclusive

For Health Controls:

1. Age 18-65, inclusive

Exclusion Criteria:

For MS Patients:

1. Prior known COVID-19 infection

For Health Controls:

1. Prior known COVID-19 infection
2. major autoimmune disorders or current treatment with immunosuppressive or immunomodulatory drugs

Primary outcomes:
measure: Primary endpoint
timeFrame: 11-12 months
Secondary outcomes:
measure: Secondary endpoint 1
timeFrame: 11-12 months
measure: Secondary endpoint 2
timeFrame: 5-6 months
measure: Secondary endpoint 3
timeFrame: 11-12 months
measure: Secondary endpoint 4
timeFrame: 11-12 months
measure: Secondary endpoint 5
timeFrame: 11-12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham MS Center
state: Massachusetts
Study officials:
References:
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