Phase III Study With Teriflunomide Versus Placebo in Patients With First Clinical Symptom of Multiple Sclerosis (TOPIC)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Multiple Sclerosis

Treatments: Drug: Teriflunomide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00622700

HMR1726D-3005 (Other Identifier)

2006-001152-12 (EudraCT Number)

EFC6260

Details and patient eligibility

About

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

Full 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.

Enrollment: 618 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• First acute or subacute, well-defined neurological event consistent with demyelination (that is, optic neuritis confirmed by an ophthalmologist, spinal cord syndrome, brainstem/cerebellar syndromes)
• Onset of MS symptoms occurring within 90 days of randomization
• A screening MRI scan with 2 or more T2 lesions at least 3 millimeter (mm) in diameter that are characteristic of MS

Exclusion criteria

• Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease
• Significantly impaired bone marrow function
• Pregnancy or nursing
• Alcohol or drug abuse
• Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment
• 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 participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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618 participants in 3 patient groups, including a placebo group

Placebo/Teriflunomide 7 mg or Teriflunomide 14 mg

Placebo Comparator group

Description:

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.

Treatment:

Drug: Teriflunomide

Drug: Placebo

Teriflunomide 7 mg/7 mg

Experimental group

Description:

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

Treatment:

Drug: Teriflunomide

Teriflunomide 14 mg/14 mg

Experimental group

Description:

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

Treatment:

Drug: Teriflunomide