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

NCT01403376 | Completed Phase 2 Results

• 3 other identifiers: PDY116842011-001160-21U1111-1115-2742
• Study Type: interventional
• Target: 128
• Locations: 5 countries
• Sites: 14

Brief 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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination

  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

  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

Study Arms (3)

Teriflunomide 7 mg

EXPERIMENTAL

Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months

Drug: teriflunomide; Biological: Influenza vaccine

Teriflunomide 14 mg

EXPERIMENTAL

Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months

Drug: teriflunomide; Biological: Influenza vaccine

IFN-β-1

ACTIVE COMPARATOR

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; Biological: Influenza vaccine

Interventions

teriflunomide DRUG

Film-coated tablet Oral administration

Also known as: HMR1726

Teriflunomide 14 mg; Teriflunomide 7 mg

Interferon-β-1 DRUG

Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection

Also known as: Rebif®, Avonex®, Betaseron®, Betaferon®, Extavia®, Genfaxone®

IFN-β-1

Influenza vaccine BIOLOGICAL

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

IFN-β-1; Teriflunomide 14 mg; Teriflunomide 7 mg

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (14)

Investigational Site Number 040001

Vienna, 1010, Austria

Location

Investigational Site Number 124005

Calgary, T2N 2T9, Canada

Location

Investigational Site Number 124003

Greenfield Park, J4V 2J2, Canada

Location

Investigational Site Number 124002

London, N6A 5A5, Canada

Location

Investigational Site Number 124007

Montreal, H3A 2B4, Canada

Location

Investigational Site Number 124008

Ottawa, K1H 8L6, Canada

Location

Investigational Site Number 124001

Québec, G1J 1Z4, Canada

Location

Investigational Site Number 124009

Toronto, M5B 1W8, Canada

Location

Investigational Site Number 276003

Berlin, 10785, Germany

Location

Investigational Site Number 276001

Essen, 45122, Germany

Location

Investigational Site Number 276002

Münster, 48149, Germany

Location

Investigational Site Number 643002

Nizhny Novgorod, 603076, Russia

Location

Investigational Site Number 804002

Ivano-Frankivsk, 76008, Ukraine

Location

Investigational Site Number 804001

Kharkiv, 61018, Ukraine

Location

Related 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):552-8. doi: 10.1212/WNL.0b013e31829e6fbf. Epub 2013 Jul 12.

  PMID: 23851964 RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

teriflunomide; Interferon beta-1a; Interferon beta-1b; Influenza Vaccines

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact_US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2011
• First Posted: July 27, 2011
• Study Start: September 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: February 18, 2016
• Results First Posted: February 26, 2013

Record last verified: 2016-01

Locations

UA (2); AU (1); DE (3); CA (7); RU (1)