A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis (TENERE)
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Purpose
Primary objective was to assess the effectiveness evaluated by the time to failure of two doses of teriflunomide in comparison to interferon beta-1a in patients with relapsing Multiple Sclerosis [MS].
Secondary objectives were:
To assess the effect of the two doses in comparison to interferon beta-1a on:
- Frequency of relapses,
- Fatigue,
- Patient's satisfaction with treatment.
- To evaluate the safety and tolerability of the two doses in comparison to interferon beta-1a.
The study consisted of a core treatment period with a common end date defined as 48 weeks after randomization of the last participant, followed by an optional long-term extension treatment period until teriflunomide is commercially available in accordance with local regulations.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Sclerosis |
Drug: interferon β-1a Drug: teriflunomide |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Multi-center, Randomized, Parallel-group, Rater-blinded Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis Plus a Long Term Extension Period |
- Overview of Failures [ Time Frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled ] [ Designated as safety issue: No ]
Failure was defined as the first occurence of confirmed relapse or permanent treatment discontinuation (for any cause) which ever came first. If no events occurred, the participant was considered free of failure.
Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores.
- Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints [ Time Frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled ] [ Designated as safety issue: No ]
Probability of disability progression at 24, 48 and 96 weeks was estimated using Kaplan-Meier method on the time to failure defined as the time from randomization to failure. Participants free of failure were censored at the date of last treatment.
Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.
- Annualized Relapse Rate [ARR]: Poisson Regression Estimates [ Time Frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled ] [ Designated as safety issue: No ]
ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.
To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and baseline EDSS stratum as covariates).
- Change From Baseline in Fatigue Impact Scale (FIS) Total Score [ Time Frame: baseline (before randomization) and 48 weeks ] [ Designated as safety issue: No ]
FIS is a subject-reported scale that qualifies the impact of fatigue on daily life in patients with MS. It consists of 40 statements that measure fatigue in three areas; physical, cognitive, and social.
FIS total score ranges from 0 (no problem) to 160 (extreme problem).
Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors).
- Treatment Satisfaction Questionnaire for Medication [TSQM] Scores [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
TSQM version 1.4 is an instrument to assess patients' satisfaction with medication. It consists of 13 questions that cover three dimensions (effectiveness, side effects and convenience) plus a global satisfaction question.
Four scores ranging from 0 to 100 (extremely satisfied) are obtained.
Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on TSQM score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction as factors).
- Overview of Adverse Events [AE] [ Time Frame: from first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first ] [ Designated as safety issue: Yes ]AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
| Enrollment: | 324 |
| Study Start Date: | April 2009 |
| Estimated Study Completion Date: | June 2015 |
| Primary Completion Date: | September 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Teriflunomide 7 mg
Teriflunomide 7 mg once daily (core treatment period), then optional, Teriflunomide 14 mg once daily (extension treatment period). |
Drug: teriflunomide
Film-coated tablet Oral administration Other Name: HMR1726
|
|
Experimental: Teriflunomide 14 mg
Teriflunomide 14 mg once daily (core treatment period), then optional, Teriflunomide 14 mg once daily (extension treatment period). |
Drug: teriflunomide
Film-coated tablet Oral administration Other Name: HMR1726
|
|
Active Comparator: IFN-β-1a
Interferon β-1a 3 times a week (core treatment period), then optional, Teriflunomide 14 mg once daily (extension treatment period). |
Drug: interferon β-1a
Sterile preservative-free solution packaged in graduated pre-filled syringes Subcutaneous injection Ascending doses from 8.8 to 44 mcg according to local standard for Rebif® Other Name: Rebif®
Drug: teriflunomide
Film-coated tablet Oral administration Other Name: HMR1726
|
Detailed Description:
The core treatment period per participant was variable depending on the enrollment in the study (maximum of approximatively 118 weeks). The two doses of teriflunomide were administered in double-blind fashion, whereas interferon beta-1a (Rebif®) was open-label.
The opportunity to continue with the highest dose of teriflunomide in open-label fashion was offered to the participants who successfully completed treatment in the core study.
The overall treatment period was followed by a 4-week elimination follow-up period.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Relapsing form of MS meeting McDonald's criteria for MS diagnosis and Expanded Disability Status Scale [EDSS] score ≤5.5 at screening visit.
Exclusion Criteria:
- Significantly impaired bone marrow function or, significant anemia, leukopenia or thrombocytopenia;
- Persistent significant or severe infection;
- Liver function impairment or known history of hepatitis;
- Use of adrenocorticotrophic hormone [ACTH] or systemic corticosteroids for 2 weeks prior to randomization;
- Human immunodeficiency virus [HIV] positive;
- Prior use of Rebif®, or prior or concomitant use of other interferons in the 3 months prior to randomization;
- Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate, mycophenolate, or natalizumab;
- Pregnant or breast-feeding woman;
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Contacts and Locations
Show 54 Study Locations| Study Director: | Clinical Sciences & Operations | Sanofi |
More Information
No publications provided
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT00883337 History of Changes |
| Other Study ID Numbers: | EFC10891, 2008-006226-34 |
| Study First Received: | April 16, 2009 |
| Results First Received: | October 3, 2012 |
| Last Updated: | January 2, 2013 |
| Health Authority: | Spain: Ethics Committee |
Keywords provided by Sanofi:
|
Relapsing-remitting multiple sclerosis |
Additional relevant MeSH terms:
|
Multiple Sclerosis Sclerosis Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases Pathologic Processes Interferon-beta |
Interferons Interferon beta 1a Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Adjuvants, Immunologic |
ClinicalTrials.gov processed this record on May 23, 2013