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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01403376
First received: July 14, 2011
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: teriflunomide
Drug: Interferon-β-1
Biological: Influenza vaccine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination [ Time Frame: 28 days post vaccination ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination [ Time Frame: pre vaccination (baseline) and 28 days post vaccination ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With 4 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination [ Time Frame: pre vaccination (baseline) and 28 days post vaccination ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination [ Time Frame: pre vaccination (baseline) and 28 days post vaccination ] [ Designated as safety issue: No ]
  • Immunoglobulin Levels [ Time Frame: pre vaccination (baseline) and 28 days post vaccination ] [ Designated as safety issue: No ]

Enrollment: 128
Study Start Date: September 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Teriflunomide 7 mg
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
Drug: teriflunomide

Film-coated tablet

Oral administration

Other Name: HMR1726
Biological: Influenza vaccine

Inactivated, split-virion influenza vaccine 2011-2012

One administration by intramuscular or intradermal route as per product specification

Experimental: Teriflunomide 14 mg
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
Drug: teriflunomide

Film-coated tablet

Oral administration

Other Name: HMR1726
Biological: Influenza vaccine

Inactivated, split-virion influenza vaccine 2011-2012

One administration by intramuscular or intradermal route as per product specification

Active Comparator: IFN-β-1
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
Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection
Other Names:
  • Rebif®
  • Avonex®
  • Betaseron®
  • Betaferon®
  • Extavia®
  • Genfaxone®
Biological: Influenza vaccine

Inactivated, split-virion influenza vaccine 2011-2012

One administration by intramuscular or intradermal route as per product specification


Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01403376

Locations
Austria
Investigational Site Number 040001
Wien, Austria, 1010
Canada
Investigational Site Number 124005
Calgary, Canada, T2N 2T9
Investigational Site Number 124003
Greenfield Park, Canada, J4V 2J2
Investigational Site Number 124002
London, Canada, N6A 5A5
Investigational Site Number 124007
Montreal, Canada, H3A 2B4
Investigational Site Number 124008
Ottawa, Canada, K1H 8L6
Investigational Site Number 124001
Quebec, Canada, G1J 1Z4
Investigational Site Number 124009
Toronto, Canada, M5B 1W8
Germany
Investigational Site Number 276003
Berlin, Germany, 10785
Investigational Site Number 276001
Essen, Germany, 45122
Investigational Site Number 276002
Münster, Germany, 48149
Russian Federation
Investigational Site Number 643002
Nizhny Novgorod, Russian Federation, 603076
Ukraine
Investigational Site Number 804002
Ivano-Frankovsk, Ukraine, 76008
Investigational Site Number 804001
Kharkiv, Ukraine, 61018
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01403376     History of Changes
Other Study ID Numbers: PDY11684, 2011-001160-21, U1111-1115-2742
Study First Received: July 14, 2011
Results First Received: January 22, 2013
Last Updated: January 22, 2013
Health Authority: Canada: Ethics Review Committee

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferons
Interferon-beta
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014