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

• ClinicalTrials.gov Identifier: NCT01403376
• Recruitment Status: Completed
• First Posted: July 27, 2011
• Results First Posted: February 26, 2013
• Last Update Posted: February 18, 2016
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: teriflunomide; Drug: Interferon-β-1; Biological: Influenza vaccine	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 128 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: September 2011
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: January 2012

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination [ Time Frame: 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.

Secondary Outcome Measures :

1. 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 ]
   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.
2. 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 ]
   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.
3. Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination [ Time Frame: pre vaccination (baseline) and 28 days post vaccination ]
4. Immunoglobulin Levels [ Time Frame: pre vaccination (baseline) and 28 days post vaccination ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 59 Years (Adult)
• Sexes Eligible for Study: All
• 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

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

Publications of Results:

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.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01403376
• Other Study ID Numbers: PDY11684; 2011-001160-21 ( EudraCT Number: UTN ); U1111-1115-2742 ( Other Identifier: UTN )
• First Posted: July 27, 2011
• Results First Posted: February 26, 2013
• Last Update Posted: February 18, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

Multiple Sclerosis; 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; Teriflunomide; Interferon beta-1b; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents