Multiple SclerosisPhase 2TERIVANCT01403376
Study to Investigate the Immune Response to Influenza Vaccine in Patients With Multiple Sclerosis on Teriflunomide
A Phase 2 study testing teriflunomide, Interferon-β-1 and Influenza vaccine in people with Multiple Sclerosis, run by Sanofi at 14 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- teriflunomide, Interferon-β-1 and Influenza vaccine
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 14 sitesin 5 countries
- Study dates
- Sep 2011to Jan 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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);
Show all 12Show fewer
- 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.
Trial locations and contacts
14 sites in 5 countries.
14 sites in 5 countries
Canada7 sites
Investigational Site Number 124005
Calgary, T2N 2T9
Investigational Site Number 124003
Greenfield Park, J4V 2J2
Investigational Site Number 124002
London, N6A 5A5
Investigational Site Number 124007
Montreal, H3A 2B4
Investigational Site Number 124008
Ottawa, K1H 8L6
Investigational Site Number 124001
Québec, G1J 1Z4
Investigational Site Number 124009
Toronto, M5B 1W8
Germany3 sites
Investigational Site Number 276003
Berlin, 10785
Investigational Site Number 276001
Essen, 45122
Investigational Site Number 276002
Münster, 48149
Ukraine2 sites
Investigational Site Number 804002
Ivano-Frankivsk, 76008
Investigational Site Number 804001
Kharkiv, 61018
About this study
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
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.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- teriflunomide, Interferon-β-1, Influenza vaccine
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
teriflunomideDrug
Also called HMR1726
Film-coated tablet
Oral administration
Interferon-β-1Drug
Also called Rebif®, Avonex®, Betaseron®, Betaferon®
Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection
Influenza vaccineBiological
Inactivated, split-virion influenza vaccine 2011-2012
One administration by intramuscular or intradermal route as per product specification
| Study group | Role | What they receive |
|---|---|---|
| Teriflunomide 7 mg | Experimental | Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months Receives: Drug: teriflunomide; Biological: Influenza vaccine |
| Teriflunomide 14 mg | Experimental | Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months Receives: 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 Receives: Drug: Interferon-β-1; Biological: Influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days post vaccination
Secondary outcomes (4)
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.
Measured: 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
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.
Measured: pre vaccination (baseline) and 28 days post vaccination
Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination
Measured: pre vaccination (baseline) and 28 days post vaccination
Immunoglobulin Levels
Measured: pre vaccination (baseline) and 28 days post vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2011 (estimated)
- Study startSep 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01403376
- Sponsor's protocol ID
- PDY11684
- Other IDs
- 2011-001160-21, U1111-1115-2742
- Acronym
- TERIVA
- Status last verified
- Jan 2016
- First submitted
- 14 Jul 2011
- Last updated
- 18 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23851964
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01403376
- Acronym / sponsor ID
- TERIVA / PDY11684
- Conditions
- Multiple Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 27 Jul 2011 (estimated)
- Results
- Posted 26 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Teriflunomide 7 mg | Experimental | Drug: teriflunomide, Biological: Influenza vaccineInfluenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months |
| Teriflunomide 14 mg | Experimental | Drug: teriflunomide, Biological: Influenza vaccineInfluenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months |
| IFN-β-1 | Active comparator | Drug: Interferon-β-1, Biological: Influenza vaccineInfluenza vaccine in participants treated with a stable dose of Interferon-β-1 (IFN-β-1) for at least 6 months |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| teriflunomideAlso: HMR1726Film-coated tablet Oral administration | Drug | Teriflunomide 14 mg, Teriflunomide 7 mg |
| Interferon-β-1Also: Rebif®, Avonex®, Betaseron®, Betaferon®Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection | Drug | IFN-β-1 |
| Influenza vaccineInactivated, split-virion influenza vaccine 2011-2012 One administration by intramuscular or intradermal route as per product specification | Biological | IFN-β-1, Teriflunomide 14 mg, Teriflunomide 7 mg |
Primary outcome
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.
4 secondary outcomes
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
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
Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination
Time frame: pre vaccination (baseline) and 28 days post vaccination
Immunoglobulin Levels
Time frame: pre vaccination (baseline) and 28 days post vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23851964Bar-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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
14 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing teriflunomide, Interferon-β-1 and Influenza vaccine in people with Multiple Sclerosis, run by Sanofi at 14 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Canada, Germany, Ukraine, Austria, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination (time frame: 28 days post vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01403376, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2016.