Clinical trial NCT00489489: Phase II Study of Teriflunomide as Adjunctive Therapy to Interferon-beta in Subjects With Multiple Sclerosis
Official title: A Randomized, Multinational, Double-Blind, Placebo-Controlled, Parallel-Group Design Pilot Study to Estimate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamic Effects of Teriflunomide for 24 Weeks When Added to Treatment With Interferon-beta in Subjects With Multiple Sclerosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: MS
interferon-beta
adjunctive therapy
relapses
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2007-06-21
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective was to estimate the tolerability and safety of 2 doses of teriflunomide administered once daily for 24 weeks, compared with placebo, in patients with multiple sclerosis \[MS\] with relapses who were on a stable dose of interferon-β \[IFN-β\].

Secondary objectives were:

* to estimate the effects of the 2 doses of teriflunomide, compared to placebo, in combination with a stable dose of IFN-β on Magnetic Resonance Imaging \[MRI\] parameters, relapse rate and patient-reported fatigue;
* to perform pharmacokinetic analyses of the 2 doses of teriflunomide in combination with a stable dose of IFN-β.

Detailed description: The study period per participant was approximatively 44 weeks broken down as follows:

* Screening period up to 4 weeks,
* 24-week double-blind treatment period\*,
* 16-week post-treatment elimination follow-up period.

'\*' participants successfully completing the week 24 visit were offered the opportunity to enter the optional long-term extension study LTS6047 - NCT00811395.

Eligibility criteria: Inclusion Criteria:

* Definite MS diagnosis according to McDonald's criteria;
* Relapsing clinical course, with or without progression;
* Expanded Disability Status Scale \[EDSS\] less or equal to 5.5 (ambulatory);
* Stable dose of IFN-β for at least 26 weeks prior to the screening visit;
* No onset of MS relapse in the preceding 60 days prior to randomization;
* Clinically stable for 4 weeks prior to randomization.

Exclusion Criteria:

* Other chronic disease of the immune system, liver function impairment or chronic pancreatic disease;
* Pregnant or nursing woman;
* Alcohol or drug abuse;
* Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment;
* Human immunodeficiency virus \[HIV\] positive status;
* Any known condition or circumstance that would prevent in the investigator's opinion compliance or completion of the study.

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

Primary outcomes:
measure: Overview of Adverse Events [AE]
timeFrame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
measure: Overview of AE With Potential Risk of Occurrence
timeFrame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
measure: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)
timeFrame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
Secondary outcomes:
measure: Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
timeFrame: baseline (before randomization) and 24 weeks
measure: Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
timeFrame: 24 weeks
measure: Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan
timeFrame: 24 weeks
measure: Annualized Relapse Rate [ARR]: Poisson Regression Estimates
timeFrame: 24 weeks
measure: Pharmacokinetic [PK]: Teriflunomide Plasma Concentration
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Milan
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: ICD
role: STUDY_DIRECTOR
References:
citation: Freedman MS, Wolinsky JS, Wamil B, Confavreux C, Comi G, Kappos L, Olsson TP, Miller A, Benzerdjeb H, Li H, Simonson C, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center. Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012 Jun 5;78(23):1877-85. doi: 10.1212/WNL.0b013e318258f7d4. Epub 2012 May 23.