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

NCT00883337 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC108912008-006226-34
• Study Type: interventional
• Target: 324
• Locations: 13 countries
• Sites: 54

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.

Conditions

Multiple Sclerosis

Keywords

Relapsing-remitting multiple sclerosis

Outcome Measures

Primary Outcomes (2)

• Core Treatment Period: 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

• Core Treatment Period: 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

Secondary Outcomes (6)

• Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates

  Core treatment period between 48 and 118 weeks depending on when the participant was enrolled

• Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score

  Baseline (before randomization) and 48 weeks

• Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores

  48 weeks

• Core Treatment Period: Overview of Adverse Events [AE]

  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

• Extension Treatment Period: Overview of AEs

  From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period

Study Arms (3)

Teriflunomide 7 mg / 14 mg

EXPERIMENTAL

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

Drug: Teriflunomide

Teriflunomide 14 mg / 14 mg

EXPERIMENTAL

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

Drug: Teriflunomide

IFN-β-1a / 14 mg

ACTIVE COMPARATOR

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

Drug: Interferon β-1a; Drug: Teriflunomide

Interventions

Interferon β-1a 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®

Also known as: Rebif®

IFN-β-1a / 14 mg

Teriflunomide DRUG

Film-coated tablet Oral administration

Also known as: HMR1726

IFN-β-1a / 14 mg; Teriflunomide 14 mg / 14 mg; Teriflunomide 7 mg / 14 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsing form of MS meeting McDonald's criteria for MS diagnosis and Expanded Disability Status Scale \[EDSS\] score ≤5.5 at screening visit.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (54)

Investigational Site Number 056003

Brussels, 1070, Belgium

Location

Investigational Site Number 056001

Ghent, 9000, Belgium

Location

Investigational Site Number 056002

Hasselt, B-3590, Belgium

Location

Investigational Site Number 124003

Lévis, G6V 3Z1, Canada

Location

Investigational Site Number 124002

London, N6A 5A5, Canada

Location

Investigational Site Number 124004

St. John's, A1B 3V6, Canada

Location

Investigational Site Number 203004

Jihlava, 58633, Czechia

Location

Investigational Site Number 203003

Prague, 10034, Czechia

Location

Investigational Site Number 203002

Prague, 12808, Czechia

Location

Investigational Site Number 250003

Bordeaux, 33076, France

Location

Investigational Site Number 250005

Clermont-Ferrand, 63003, France

Location

Investigational Site Number 250004

Lille, 59037, France

Location

Investigational Site Number 250001

Montpellier, 34000, France

Location

Investigational Site Number 250002

Strasbourg, 67091, France

Location

Investigational Site Number 276003

Bad Mergentheim, 97980, Germany

Location

Investigational Site Number 276011

Berlin, 10117, Germany

Location

Investigational Site Number 276012

Berlin, 12099, Germany

Location

Investigational Site Number 276001

Bochum, 44791, Germany

Location

Investigational Site Number 276005

Dresden, 01307, Germany

Location

Investigational Site Number 276007

Erbach im Odenwald, 64711, Germany

Location

Investigational Site Number 276006

Essen, 45138, Germany

Location

Investigational Site Number 276004

Halle, 06120, Germany

Location

Investigational Site Number 276010

Hanover, 30559, Germany

Location

Investigational Site Number 276009

Mainz, 55131, Germany

Location

Investigational Site Number 276002

Münster, 48149, Germany

Location

Investigational Site Number 300001

Athens, 11527, Greece

Location

Investigational Site Number 300002

Thessaloniki, Greece

Location

Investigational Site Number 348001

Budapest, 1083, Hungary

Location

Investigational Site Number 348005

Budapest, 1096, Hungary

Location

Investigational Site Number 348003

Budapest, 1106, Hungary

Location

Investigational Site Number 348002

Esztergom, 2500, Hungary

Location

Investigational Site Number 348007

Kecskemét, 6000, Hungary

Location

Investigational Site Number 348004

Veszprém, 8200, Hungary

Location

Investigational Site Number 380010

Ancona, 60020, Italy

Location

Investigational Site Number 380005

Bari, 70124, Italy

Location

Investigational Site Number 380008

Cagliari, 09126, Italy

Location

Investigational Site Number 380003

Cefalù, 90015, Italy

Location

Investigational Site Number 380007

Genova, 16132, Italy

Location

Investigational Site Number 380001

Milan, 20132, Italy

Location

Investigational Site Number 380004

Pavia, 27100, Italy

Location

Investigational Site Number 380002

Roma, 00185, Italy

Location

Investigational Site Number 380006

Torino, 10126, Italy

Location

Investigational Site Number 616002

Bialystok, 15-276, Poland

Location

Investigational Site Number 616004

Gdansk, 80-803, Poland

Location

Investigational Site Number 616003

Lublin, 20-718, Poland

Location

Investigational Site Number 616001

Warsaw, 02-957, Poland

Location

Investigational Site Number 724007

Barcelona, 08036, Spain

Location

Investigational Site Number 724001

Bilbao, 48013, Spain

Location

Investigational Site Number 724002

Majadahonda, 28222, Spain

Location

Investigational Site Number 724003

Murcia, 30120, Spain

Location

Investigational Site Number 756002

Sankt Gallen, 9007, Switzerland

Location

Investigational Site Number 788002

Monastir, 5000, Tunisia

Location

Investigational Site Number 826002

London, SW17 0QT, United Kingdom

Location

Investigational Site Number 826003

Plymouth, PL6 5BX, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 24126064 RESULT

• 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.

  PMID: 33023488 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Interventions

Interferon beta-1a; teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Trial Transparency Team
• Organization: sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2009
• First Posted: April 17, 2009
• Study Start: April 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: May 1, 2015
• Last Updated: June 13, 2016
• Results First Posted: November 6, 2012

Record last verified: 2016-05

Locations

CA (3); CH (1); BE (3); HU (6); TU (1); CZ (3); GR (2); ES (4); DE (11); GB (2); IT (9); FR (5); PL (4)