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

Multiple Sclerosis Clinical Trial

— TENERE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00883337
• Other study ID #: EFC10891
• Secondary ID: 2008-006226-34
• Status: Completed
• Phase: Phase 3
• First received: April 16, 2009
• Last updated: June 1, 2015
• Start date: April 2009
• Est. completion date: May 2015

Study information

• Verified date: June 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. completion date: May 2015
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• interferon ß-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®
• teriflunomide
Film-coated tablet Oral administration

Locations

Country	Name	City	State
Belgium	Investigational Site Number 056003	Bruxelles
Belgium	Investigational Site Number 056001	Gent
Belgium	Investigational Site Number 056002	Hasselt
Canada	Investigational Site Number 124003	Lévis
Canada	Investigational Site Number 124002	London
Canada	Investigational Site Number 124004	St. John'S
Czech Republic	Investigational Site Number 203004	Jihlava
Czech Republic	Investigational Site Number 203003	Praha 10
Czech Republic	Investigational Site Number 203002	Praha 2
France	Investigational Site Number 250003	Bordeaux Cedex
France	Investigational Site Number 250005	Clermont Ferrand Cedex 1
France	Investigational Site Number 250004	Lille Cedex
France	Investigational Site Number 250001	Montpellier Cedex 5
France	Investigational Site Number 250002	Strasbourg Cedex
Germany	Investigational Site Number 276003	Bad Mergentheim
Germany	Investigational Site Number 276011	Berlin
Germany	Investigational Site Number 276012	Berlin
Germany	Investigational Site Number 276001	Bochum
Germany	Investigational Site Number 276005	Dresden
Germany	Investigational Site Number 276007	Erbach
Germany	Investigational Site Number 276006	Essen
Germany	Investigational Site Number 276004	Halle/Saale
Germany	Investigational Site Number 276010	Hannover
Germany	Investigational Site Number 276009	Mainz
Germany	Investigational Site Number 276002	Münster
Greece	Investigational Site Number 300001	Athens
Greece	Investigational Site Number 300002	Thessaloniki
Hungary	Investigational Site Number 348001	Budapest
Hungary	Investigational Site Number 348003	Budapest
Hungary	Investigational Site Number 348005	Budapest
Hungary	Investigational Site Number 348002	Esztergom
Hungary	Investigational Site Number 348007	Kecskemét
Hungary	Investigational Site Number 348004	Veszprém
Italy	Investigational Site Number 380010	Ancona
Italy	Investigational Site Number 380005	Bari
Italy	Investigational Site Number 380008	Cagliari
Italy	Investigational Site Number 380003	Cefalù
Italy	Investigational Site Number 380007	Genova
Italy	Investigational Site Number 380001	Milano
Italy	Investigational Site Number 380004	Pavia
Italy	Investigational Site Number 380002	Roma
Italy	Investigational Site Number 380006	Torino
Poland	Investigational Site Number 616002	Bialystok
Poland	Investigational Site Number 616004	Gdansk
Poland	Investigational Site Number 616003	Lublin
Poland	Investigational Site Number 616001	Warszawa
Spain	Investigational Site Number 724007	Barcelona
Spain	Investigational Site Number 724001	Bilbao
Spain	Investigational Site Number 724002	Majadahonda
Spain	Investigational Site Number 724003	Murcia
Switzerland	Investigational Site Number 756002	St. Gallen
Tunisia	Investigational Site Number 788002	Monastir
United Kingdom	Investigational Site Number 826002	London
United Kingdom	Investigational Site Number 826003	Plymouth

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Belgium,  Canada,  Czech Republic,  France,  Germany,  Greece,  Hungary,  Italy,  Poland,  Spain,  Switzerland,  Tunisia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overview of Failures	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.	Core treatment period between 48 and 118 weeks depending on when the participant was enrolled	No
Primary	Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints	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.	Core treatment period between 48 and 118 weeks depending on when the participant was enrolled	No
Secondary	Annualized Relapse Rate [ARR]: Poisson Regression Estimates	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).	Core treatment period between 48 and 118 weeks depending on when the participant was enrolled	No
Secondary	Change From Baseline in Fatigue Impact Scale (FIS) Total Score	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).	baseline (before randomization) and 48 weeks	No
Secondary	Treatment Satisfaction Questionnaire for Medication [TSQM] Scores	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).	48 weeks	No
Secondary	Overview of Adverse Events [AE]	AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.	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	Yes