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

NCT ID: NCT00883337

Last Updated: 2016-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 324 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2015-05-31

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Teriflunomide 7 mg / 14 mg

Teriflunomide 7 mg once daily (core treatment period) and teriflunomide 14 mg once daily (extended treatment period).

Group Type: EXPERIMENTAL

Teriflunomide

Intervention Type: DRUG

Film-coated tablet

Oral administration

Teriflunomide 14 mg / 14 mg

Teriflunomide 14 mg once daily (core treatment period) and teriflunomide 14 mg once daily (extension treatment period).

Group Type: EXPERIMENTAL

Teriflunomide

Intervention Type: DRUG

Film-coated tablet

Oral administration

IFN-β-1a / 14 mg

Interferon β-1a 3 times a week (core treatment period) and teriflunomide 14 mg once daily (extended treatment period).

Group Type: ACTIVE_COMPARATOR

Interferon β-1a

Intervention Type: DRUG

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

Intervention Type: DRUG

Film-coated tablet

Oral administration

Interventions

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®

Intervention Type: DRUG

Teriflunomide

Film-coated tablet

Oral administration

Intervention Type: DRUG

Other Intervention Names

Rebif®; HMR1726

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 056003

Brussels, , Belgium

Investigational Site Number 056001

Ghent, , Belgium

Investigational Site Number 056002

Hasselt, , Belgium

Investigational Site Number 124003

Lévis, , Canada

Investigational Site Number 124002

London, , Canada

Investigational Site Number 124004

St. John's, , Canada

Investigational Site Number 203004

Jihlava, , Czechia

Investigational Site Number 203003

Prague, , Czechia

Investigational Site Number 203002

Prague, , Czechia

Investigational Site Number 250003

Bordeaux, , France

Investigational Site Number 250005

Clermont-Ferrand, , France

Investigational Site Number 250004

Lille, , France

Investigational Site Number 250001

Montpellier, , France

Investigational Site Number 250002

Strasbourg, , France

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 im Odenwald, , Germany

Investigational Site Number 276006

Essen, , Germany

Investigational Site Number 276004

Halle, , Germany

Investigational Site Number 276010

Hanover, , Germany

Investigational Site Number 276009

Mainz, , Germany

Investigational Site Number 276002

Münster, , Germany

Investigational Site Number 300001

Athens, , Greece

Investigational Site Number 300002

Thessaloniki, , Greece

Investigational Site Number 348001

Budapest, , Hungary

Investigational Site Number 348005

Budapest, , Hungary

Investigational Site Number 348003

Budapest, , Hungary

Investigational Site Number 348002

Esztergom, , Hungary

Investigational Site Number 348007

Kecskemét, , Hungary

Investigational Site Number 348004

Veszprém, , Hungary

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

Milan, , Italy

Investigational Site Number 380004

Pavia, , Italy

Investigational Site Number 380002

Roma, , Italy

Investigational Site Number 380006

Torino, , Italy

Investigational Site Number 616002

Bialystok, , Poland

Investigational Site Number 616004

Gdansk, , Poland

Investigational Site Number 616003

Lublin, , Poland

Investigational Site Number 616001

Warsaw, , Poland

Investigational Site Number 724007

Barcelona, , Spain

Investigational Site Number 724001

Bilbao, , Spain

Investigational Site Number 724002

Majadahonda, , Spain

Investigational Site Number 724003

Murcia, , Spain

Investigational Site Number 756002

Sankt Gallen, , Switzerland

Investigational Site Number 788002

Monastir, , Tunisia

Investigational Site Number 826002

London, , United Kingdom

Investigational Site Number 826003

Plymouth, , United Kingdom

Countries

Belgium; Canada; Czechia; France; Germany; Greece; Hungary; Italy; Poland; Spain; Switzerland; Tunisia; United Kingdom

References

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.

Reference Type: RESULT

PMID: 24126064 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33023488 (View on PubMed)

Other Identifiers

2008-006226-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC10891

Identifier Type: -

Identifier Source: org_study_id