A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis (TENERE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00883337
First received: April 16, 2009
Last updated: July 23, 2014
Last verified: July 2014
  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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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: March 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
Criteria

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
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: NCT00883337

  Show 54 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: July 23, 2014
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 1a
Interferon-beta
Interferons
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 27, 2014