Immune Response to COVID-19 Vaccine in Multiple Sclerosis Patients Treated With Teriflunomide and Alemtuzumab

Study Overview
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Brief Summary
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Phase IV, 3-armed, prospective, open-label, single-center, Israeli study, examining the response to SARS-CoV-2 vaccination in 30 teriflunomide-, 10 alemtuzumab-treated patients, and 30 age-matched (for the teriflunomide group) untreated MS patients. Treatments will be administered according to common local practice. Demographic, clinical, treatment-related and COVID-19-related data will be collected. Blood samples will be drawn for each participant at baseline (before COVID-19 vaccination), and at 1, 3, 6, (and possibly 12) months post 2nd dose of COVID-19 vaccine. Humoral, B-cell and T-cell responses will be evaluated.

Official Title
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LONGEVITY OF IMMUNE RESPONSE TO COVID-19 VACCINE IN VACCINATED MULTIPLE SCLEROSIS PATIENTS TREATED WITH TERIFLUNOMIDE (AUBAGIO) OR ALEMTUZUMAB (LEMTRADA)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: COVID-19 vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Diagnosis of multiple sclerosis (MS) according to 2017 McDonald criteria. (2) Age >=18 years. (3) Treatment with Teriflunomide for at least 6 months/or 4 to 18 months after the last course treatment with Alemtuzumab/or untreated. (4) Signed written informed consent. Exclusion Criteria: (1) Cognitive decline that precludes understanding the study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MS no immunomodulatory treatment<br>MS patients receiving no immunomodulatory treatment | Biological: COVID-19 vaccination<br>* Blood sample obtained before, 1 , 3 and 6 months after the intervention<br>* Other names: Blood withdrawn;|
| Active Comparator: MS Teriflunomide treatment<br>MS patients under treatment with Teriflunomide | Biological: COVID-19 vaccination<br>* Blood sample obtained before, 1 , 3 and 6 months after the intervention<br>* Other names: Blood withdrawn;|
| Active Comparator: MS Alemtuzumab treatment<br>MS patients under treatment with Alemtuzumab | Biological: COVID-19 vaccination<br>* Blood sample obtained before, 1 , 3 and 6 months after the intervention<br>* Other names: Blood withdrawn;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of SARS-COV-2 antibody positive MS COVID-19 vaccinees at 1-month post 2nd COVID-19 vaccine dose. | Detection of SARS-CoV-2 IgG antibodies in blood samples will be performed using Euroimmun (EI, Lubeck, Germany) anti-SARS-CoV-2 IgG quantitative ELISA kit based on a recombinant S1 subunit of the SARS-CoV-2 spike protein | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of SARS-COV-2 antibody positive MS COVID-19 vaccinees at 3 and 6 months post 2nd COVID-19 vaccination. | Detection of SARS-CoV-2 IgG antibodies in blood samples will be performed using Euroimmun (EI, Lubeck, Germany) anti-SARS-CoV-2 IgG quantitative ELISA kit based on a recombinant S1 subunit of the SARS-CoV-2 spike protein | 12months | 
| SARS-COV-2 antibody titer at 1,3 and 6 months post 2nd COVID-19 vaccination. | Detection of SARS-CoV-2 IgG antibodies in blood samples will be performed using Euroimmun (EI, Lubeck, Germany) anti-SARS-CoV-2 IgG quantitative ELISA kit based on a recombinant S1 subunit of the SARS-CoV-2 spike protein | 12 months | 
| SARS-COV-2 B-cell memory response at 1,3 and 6 months post 2nd COVID-19 vaccination. | Reversed antigen human IgG SARS-CoV-2 receptor-binding domain (RBD) ELISpotPLUS will be used according to the manufacturer instructions. | 12 months | 
| Percent of MS COVID-19 vaccinees with SARS-COV-2 T-cell memory positive response at 1,3 and 6 months post 2nd COVID-19 vaccination. | Positive T cell response will be calculated according to the highest number of IFN-γ/IL-2 secreting cells in the FluoroSpot | 12 months | 
| SARS-COV-2 T-cell memory response at 1,3 and 6 months post 2nd COVID-19 vaccination. | As indicated in outcome #5 | 12 months | 
| Percent of MS COVID-19 vaccinees with positive double immune response (two responses of the possible three), or positive triple immune response (IgG, T-cell and B-cell memory positive) at 6 months post 2nd COVID-19 vaccination. | Statistical analysis | 6 months | 
| Percent of MS COVID-19 vaccinees with SARS-COV-2 B-cell memory positive response at 1,3 and 6 months post 2nd COVID-19 vaccination. Positive cut-off value will be determined as higher than 10 SFU. | Statistical analysis | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Multiple sclerosis, Vaccination, Teriflunomide (Aubagio), Alemtuzumab (Lemtrada), Immune responses, IgG, B-cells, T-cells