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

Multiple Sclerosis Clinical Trial

— TERIVA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01403376
• Other study ID #: PDY11684
• Secondary ID: 2011-001160-21U1
• Status: Completed
• Phase: Phase 2
• First received: July 14, 2011
• Last updated: January 21, 2016
• Start date: September 2011
• Est. completion date: January 2012

Study information

• Verified date: January 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 59 Years

Eligibility

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-ß-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-ß-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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• teriflunomide
Film-coated tablet Oral administration
• Interferon-ß-1
Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection

Biological:
• Influenza vaccine
Inactivated, split-virion influenza vaccine 2011-2012 One administration by intramuscular or intradermal route as per product specification

Locations

Country	Name	City	State
Austria	Investigational Site Number 040001	Wien
Canada	Investigational Site Number 124005	Calgary
Canada	Investigational Site Number 124003	Greenfield Park
Canada	Investigational Site Number 124002	London
Canada	Investigational Site Number 124007	Montreal
Canada	Investigational Site Number 124008	Ottawa
Canada	Investigational Site Number 124001	Quebec
Canada	Investigational Site Number 124009	Toronto
Germany	Investigational Site Number 276003	Berlin
Germany	Investigational Site Number 276001	Essen
Germany	Investigational Site Number 276002	Münster
Russian Federation	Investigational Site Number 643002	Nizhny Novgorod
Ukraine	Investigational Site Number 804002	Ivano-Frankovsk
Ukraine	Investigational Site Number 804001	Kharkiv

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Austria,  Canada,  Germany,  Russian Federation,  Ukraine, 

References & Publications (1)

Bar-Or A, Freedman MS, Kremenchutzky M, Menguy-Vacheron F, Bauer D, Jodl S, Truffinet P, Benamor M, Chambers S, O'Connor PW. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013 Aug 6;81(6):552- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination		pre vaccination (baseline) and 28 days post vaccination	No
Secondary	Immunoglobulin Levels		pre vaccination (baseline) and 28 days post vaccination	No