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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-001160-21 | EudraCT Number | UTN | |
| U1111-1115-2742 | Other Identifier | UTN |
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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:
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.
The maximum duration of the study period for a participant was approximatively 49 days broken down as follows:
MS treatment (Teriflunomide or interferon-β-1) was to be continued during the course of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Teriflunomide 7 mg | Experimental | Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months |
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| Teriflunomide 14 mg | Experimental | Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months |
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| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| teriflunomide | Drug | Film-coated tablet Oral administration |
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| 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 |
| 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 |
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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:
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Site Number 040001 | Vienna | 1010 | Austria | |||
| Investigational Site Number 124005 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23851964 | Result | 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. |
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In order to ensure at least 40 participants were enrolled in the teriflunomide 14 mg group while maintaining the blind in the study LTS6050 an interactive voice response system (IVRS) was set up to include participants from both studies LTS6048 and LTS6050 into this study.
128 participants were enrolled and vaccinated at 14 sites.
The recruitment initiated in September 2011 was completed in December 2011. A total of 137 patients were screened at 14 sites in 5 countries.
Participants treated with teriflunomide were recruited in the LTS6048-NCT00228163 study and in the LTS6050-NCT00803049 study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Teriflunomide 7 mg | Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months |
| FG001 | Teriflunomide 14 mg | Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Interferon-β-1 | Drug | Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection |
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| Influenza vaccine | Biological | Inactivated, split-virion influenza vaccine 2011-2012 One administration by intramuscular or intradermal route as per product specification |
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| 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 |
| Calgary |
| T2N 2T9 |
| Canada |
| Investigational Site Number 124003 | Greenfield Park | J4V 2J2 | Canada |
| Investigational Site Number 124002 | London | N6A 5A5 | Canada |
| Investigational Site Number 124007 | Montreal | H3A 2B4 | Canada |
| Investigational Site Number 124008 | Ottawa | K1H 8L6 | Canada |
| Investigational Site Number 124001 | Québec | G1J 1Z4 | Canada |
| Investigational Site Number 124009 | Toronto | M5B 1W8 | Canada |
| Investigational Site Number 276003 | Berlin | 10785 | Germany |
| Investigational Site Number 276001 | Essen | 45122 | Germany |
| Investigational Site Number 276002 | Münster | 48149 | Germany |
| Investigational Site Number 643002 | Nizhny Novgorod | 603076 | Russia |
| Investigational Site Number 804002 | Ivano-Frankivsk | 76008 | Ukraine |
| Investigational Site Number 804001 | Kharkiv | 61018 | Ukraine |
| FG002 | IFN-β-1 | Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Teriflunomide 7 mg | Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months |
| BG001 | Teriflunomide 14 mg | Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months |
| BG002 | IFN-β-1 | Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| pre-vaccination antibody titer - H1N1 strain | H1N1, H3N2 and B were the strains contained in the seasonal influenza vaccine used. | Number | participants |
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| pre-vaccination antibody titer - H3N2 strain | Number | participants |
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| pre-vaccination antibody titer - B strain | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Per-protocol population: Enrolled and vaccinated participants with antibody assessments at Day 28, but excluding those with important events/deviations potentially impacting analysis (multiple sclerosis relapse, poor compliance to treatment, interfering concomitant drug). Participants were considered according to the treatment actually received. | Posted | Number | 90% Confidence Interval | percentage of participants | 28 days post vaccination |
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| 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. | Per-protocol population as previously defined | Posted | Number | 90% Confidence Interval | percentage of participants | pre vaccination (baseline) and 28 days post vaccination |
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| 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. | Per-protocol population as previously defined | Posted | Number | 90% Confidence Interval | percentage of participants | pre vaccination (baseline) and 28 days post vaccination |
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| Secondary | Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination | Per-protocol population as previously defined | Posted | Geometric Mean | 90% Confidence Interval | ratio post/pre vaccination | pre vaccination (baseline) and 28 days post vaccination |
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| Secondary | Immunoglobulin Levels | Per-protocol population as previously defined | Posted | Mean | Standard Deviation | g/L | pre vaccination (baseline) and 28 days post vaccination |
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Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Teriflunomide 7mg | Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months | 0 | 41 | 3 | 41 | ||
| EG001 | Teriflunomide 14mg | Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months | 0 | 41 | 6 | 41 | ||
| EG002 | IFN-β-1 | Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months | 0 | 46 | 13 | 46 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Injection site pain | General disorders | MedDRA 14.1 | Non-systematic Assessment |
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If no publication has occurred within 12 months after trial completion, the Investigator can present or publish results. The Investigator provides the Sponsor with a copy of the presentation or publication for review and comment at least 30 days in advance of its submission.
The Sponsor can delay the submission for a period not exceeding 90 days to allow for filing a patent application or such other measures as the Sponsor deems appropriate to establish and preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | Contact_US@sanofi.com |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C527525 | teriflunomide |
| D000068556 | Interferon beta-1a |
| D000068576 | Interferon beta-1b |
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D016899 | Interferon-beta |
| D007370 | Interferon Type I |
| D007372 | Interferons |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| Male |
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| Between 10 and 40 (<) |
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| ≥40 |
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| Between 10 and 40 (<) |
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| ≥40 |
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| Between 10 and 40 (<) |
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| ≥40 |
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| B strain |
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