Conditions: Multiple Sclerosis
Keywords: MS Clinically Isolated Syndrome CIS CDMS relapses
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 618
Healthy volunteers: no

Brief summary:
The primary objective was to demonstrate the effect of teriflunomide (HMR1726) (14 milligram per day \[mg/day\] and 7 mg/day), in comparison to placebo, for reducing conversion of participants presenting with their first clinical episode consistent with multiple sclerosis (MS) to clinically definite multiple sclerosis (CDMS).

The secondary objectives were:

* To demonstrate the effect of teriflunomide, in comparison to placebo, on:

  * Reducing conversion to definite multiple sclerosis (DMS)
  * Reducing annualized relapse rate (ARR)
  * Reducing disease activity/progression as measured by Magnetic Resonance Imaging (MRI)
  * Reducing accumulation of disability for at least 12 weeks as measured by the Expanded Disability Status Scale (EDSS)
  * Proportion of disability-free participants as assessed by the EDSS
  * Reducing participant-reported fatigue
* To evaluate the safety and tolerability of teriflunomide
* To evaluate the pharmacokinetics (PK) of teriflunomide
* Optional pharmacogenomic testing aimed at assessing the association between the main enzyme systems of teriflunomide metabolism and hepatic safety, and other potential associations between gene variations and clinical outcomes

Detailed description:
The study consisted of 4 periods:

* Screening period: up to 4 weeks,
* Placebo-controlled treatment period: up to 108 weeks (at least 24 weeks for participants who experienced conversion to CDMS),
* Extension treatment period (without placebo-control): the extension period continued until teriflunomide was commercially available in participant's country of residence.
* Post-treatment washout period: 4 weeks after last treatment intake.

The maximal duration of the study period per participant was expected to be 116 weeks if he/she did not continue in the extension treatment period.

Arms:
arm 1: Core treatment period: Placebo matched to teriflunomide tablet once daily orally.

Extension treatment period: Re-randomized in 1:1 ratio to either teriflunomide 7 mg or 14 mg once daily orally. arm 2: Core treatment period: Teriflunomide 7 mg tablet once daily orally.

Extension treatment period: Teriflunomide 7 mg tablet once daily orally. arm 3: Core treatment period: Teriflunomide 14 mg tablet once daily orally.

Extension treatment period: Teriflunomide 14 mg tablet once daily orally.

Interventions: intervention 1: Teriflunomide intervention 2: Placebo
Intervention descriptions: intervention 1: Film-coated tablet Oral administration intervention 2: Film-coated tablet Oral administration

Protocol document: