Study to Investigate the Immune Response to Influenza Vaccine in Patients With Multiple Sclerosis on Teriflunomide

Study Overview
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Brief Summary
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Primary Objective: Assess the antibody response to influenza vaccine in patients with relapsing form of multiple sclerosis (RMS) treated with teriflunomide compared to a reference population. Secondary Objectives: Assess the effect of teriflunomide on immunoglobulin levels; Assess the safety of influenza vaccination in patients with RMS treated with teriflunomide. The reference population was defined as multiple sclerosis (MS) patients with a stable treatment with interferon-β-1. Antibody response was measured using hemagglutination inhibition assay (HIA) and the hemagglutinin antigens representing the stains of H3N2, H1N1, and B as present in the influenza vaccine used.

Detailed Description
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The maximum duration of the study period for a participant was approximatively 49 days broken down as follows: Screening period of up to 21 days; Influenza vaccination at Day 1; Follow-up period of 28 days (±2 days). MS treatment (Teriflunomide or interferon-β-1) was to be continued during the course of the study.

Official Title
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Study to Investigate the Immune Response to Influenza Vaccine in Patients With Multiple Sclerosis on Teriflunomide Treatment and Using a Population of Patients With Multiple Sclerosis as a Reference

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: teriflunomide
* Drug: Interferon-β-1
* Biological: Influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Male or female patient <60 years old with relapsing multiple sclerosis (RMS) either treated for at least 6 months with 7 or 14 mg teriflunomide in one of the studies LTS6048 or LTS6050, or treated with a stable dose of interferon-β-1 for at least 6 months. Exclusion Criteria: Concomitant infectious pathology at the time of vaccination; MS relapse within 1 month before vaccination; Systemic corticosteroids within 1 month before the vaccination; Any contraindication to influenza vaccine; Any vaccination within the last 6 months; Prior use of any investigational drug or participation to a clinical trial within 1 year (only for patients under interferon-β-1); Prior or concomitant use (for a minimum of 1 year before study entry) of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate, mycophenolate, natalizumab (Tysabri®), leflunomide or fingolimod or other immunomodulator/immunosuppressant in development; Prior or concomitant use of glatiramer acetate within 1 year before study entry; Prior or concomitant use of intravenous immunoglobulins within 3 months before study entry; Pregnant or breast feeding women; Woman of childbearing potential without adequate contraception. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriflunomide 7 mg<br>Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months | Drug: teriflunomide<br>* Film-coated tablet Oral administration<br>* Other names: HMR1726;Biological: Influenza vaccine<br>* Inactivated, split-virion influenza vaccine 2011-2012 One administration by intramuscular or intradermal route as per product specification<br>|
| Experimental: Teriflunomide 14 mg<br>Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months | Drug: teriflunomide<br>* Film-coated tablet Oral administration<br>* Other names: HMR1726;Biological: Influenza vaccine<br>* Inactivated, split-virion influenza vaccine 2011-2012 One administration by intramuscular or intradermal route as per product specification<br>|
| Active Comparator: IFN-β-1<br>Influenza vaccine in participants treated with a stable dose of Interferon-β-1 (IFN-β-1) for at least 6 months | Drug: Interferon-β-1<br>* Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection<br>* Other names: Genfaxone®;Biological: Influenza vaccine<br>* Inactivated, split-virion influenza vaccine 2011-2012 One administration by intramuscular or intradermal route as per product specification<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination | For each viral strain (H1N1, H3N2, and B), the antibody titer, level of antibodies in blood sample when exposed to antigen, was calculated as the mean of two replicates. If the titer was below or above the limit of detection, the threshold value was used. The percentage of participants achieving a titer of 40 or more, as well as the 90% confidence interval (CI) using normal approximation were calculated for each strain and treatment group. | 28 days post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination | Percentages of participants with an increase from baseline of 2-fold or more in antibody titers and 90% CIs using normal approximation were calculated for each strain and treatment group. | pre vaccination (baseline) and 28 days post vaccination | 
| Percentage of Participants With 4 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination | Percentages of participants with an increase from baseline of 4-fold or more in antibody titers and 90% CIs using normal approximation were calculated for each strain and treatment group. | pre vaccination (baseline) and 28 days post vaccination | 
| Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination |  | pre vaccination (baseline) and 28 days post vaccination | 
| Immunoglobulin Levels |  | pre vaccination (baseline) and 28 days post vaccination |