Clinical trial NCT00883337: A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Relapsing-remitting multiple sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-04-17
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 participants 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,
  * Participant'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.

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 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.

Extension criteria:

The participants who met all the following criteria at the end of the core study period were eligible for enrolment into the open-label extension phase:

* Participants who had not discontinued treatment in the core period and who had a minimum treatment of 48 weeks and completed the EOT visit (Visit 18).
* Participants who had not met criteria for treatment withdrawal.
* An informed consent must be obtained in writing from the participant for this open-label extension phase prior to entering and prior to completion of any extension phase procedure.
* Participants who demonstrated a willingness and ability to roll over to the extension phase with the opportunity to continue treatment on 14 mg/day of teriflunomide under open-label.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Core Treatment Period: Overview of Failures
timeFrame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
measure: Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints
timeFrame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
Secondary outcomes:
measure: Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates
timeFrame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
measure: Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score
timeFrame: Baseline (before randomization) and 48 weeks
measure: Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores
timeFrame: 48 weeks
measure: Core Treatment Period: Overview of Adverse Events [AE]
timeFrame: 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
measure: Extension Treatment Period: Overview of AEs
timeFrame: From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period
measure: Extension Treatment Period: ARR Poisson Regression Estimates
timeFrame: Extension treatment period (Maximum: 197 weeks)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Investigational Site Number 056003
city: Gent
country: Belgium
facility: Investigational Site Number 056001
city: Hasselt
country: Belgium
facility: Investigational Site Number 056002
city: London
country: Canada
facility: Investigational Site Number 124002
city: Lévis
country: Canada
facility: Investigational Site Number 124003
city: St. John'S
country: Canada
facility: Investigational Site Number 124004
city: Jihlava
country: Czech Republic
facility: Investigational Site Number 203004
city: Praha 10
country: Czech Republic
facility: Investigational Site Number 203003
city: Praha 2
country: Czech Republic
facility: Investigational Site Number 203002
city: Bordeaux Cedex
country: France
facility: Investigational Site Number 250003
city: Clermont Ferrand Cedex 1
country: France
facility: Investigational Site Number 250005
city: Lille Cedex
country: France
facility: Investigational Site Number 250004
city: Montpellier Cedex 5
country: France
facility: Investigational Site Number 250001
city: Strasbourg Cedex
country: France
facility: Investigational Site Number 250002
city: Bad Mergentheim
country: Germany
facility: Investigational Site Number 276003
city: Berlin
country: Germany
facility: Investigational Site Number 276011
city: Berlin
country: Germany
facility: Investigational Site Number 276012
city: Bochum
country: Germany
facility: Investigational Site Number 276001
city: Dresden
country: Germany
facility: Investigational Site Number 276005
city: Erbach
country: Germany
facility: Investigational Site Number 276007
city: Essen
country: Germany
facility: Investigational Site Number 276006
city: Halle/Saale
country: Germany
facility: Investigational Site Number 276004
city: Hannover
country: Germany
facility: Investigational Site Number 276010
city: Mainz
country: Germany
facility: Investigational Site Number 276009
city: Münster
country: Germany
facility: Investigational Site Number 276002
city: Athens
country: Greece
facility: Investigational Site Number 300001
city: Thessaloniki
country: Greece
facility: Investigational Site Number 300002
city: Budapest
country: Hungary
facility: Investigational Site Number 348001
city: Budapest
country: Hungary
facility: Investigational Site Number 348005
city: Budapest
country: Hungary
facility: Investigational Site Number 348003
city: Esztergom
country: Hungary
facility: Investigational Site Number 348002
city: Kecskemét
country: Hungary
facility: Investigational Site Number 348007
city: Veszprém
country: Hungary
facility: Investigational Site Number 348004
city: Ancona
country: Italy
facility: Investigational Site Number 380010
city: Bari
country: Italy
facility: Investigational Site Number 380005
city: Cagliari
country: Italy
facility: Investigational Site Number 380008
city: Cefalù
country: Italy
facility: Investigational Site Number 380003
city: Genova
country: Italy
facility: Investigational Site Number 380007
city: Milano
country: Italy
facility: Investigational Site Number 380001
city: Pavia
country: Italy
facility: Investigational Site Number 380004
city: Roma
country: Italy
facility: Investigational Site Number 380002
city: Torino
country: Italy
facility: Investigational Site Number 380006
city: Bialystok
country: Poland
facility: Investigational Site Number 616002
city: Gdansk
country: Poland
facility: Investigational Site Number 616004
city: Lublin
country: Poland
facility: Investigational Site Number 616003
city: Warszawa
country: Poland
facility: Investigational Site Number 616001
city: Barcelona
country: Spain
facility: Investigational Site Number 724007
city: Bilbao
country: Spain
facility: Investigational Site Number 724001
city: Majadahonda
country: Spain
facility: Investigational Site Number 724002
city: Murcia
country: Spain
facility: Investigational Site Number 724003
city: St. Gallen
country: Switzerland
facility: Investigational Site Number 756002
city: Monastir
country: Tunisia
facility: Investigational Site Number 788002
city: London
country: United Kingdom
facility: Investigational Site Number 826002
city: Plymouth
country: United Kingdom
facility: Investigational Site Number 826003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Vermersch P, Czlonkowska A, Grimaldi LM, Confavreux C, Comi G, Kappos L, Olsson TP, Benamor M, Bauer D, Truffinet P, Church M, Miller AE, Wolinsky JS, Freedman MS, O'Connor P; TENERE Trial Group. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler. 2014 May;20(6):705-16. doi: 10.1177/1352458513507821. Epub 2013 Oct 14.
citation: Comi G, Freedman MS, Meca-Lallana JE, Vermersch P, Kim BJ, Parajeles A, Edwards KR, Gold R, Korideck H, Chavin J, Poole EM, Coyle PK. Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis. BMC Neurol. 2020 Oct 6;20(1):364. doi: 10.1186/s12883-020-01937-4.