Phase 3 N=618 Randomized Double-blind Treatment

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

Multiple Sclerosis

Bottom Line

View on ClinicalTrials.gov: NCT00622700 ↗

Enrolled (actual)

618

Serious AEs

11.3%

Results posted

Dec 2014

Primary outcome: Primary: Core Treatment Period: Time to Conversion to Clinically Deﬁnite Multiple Sclerosis (CDMS) — 14.3; 8.7; 9.0; 26.0 percent probability — p=0.0087

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Teriflunomide (Drug); Placebo (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Sanofi
Primary completion: Dec 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Core Treatment Period: Time to Conversion to Clinically Deﬁnite Multiple Sclerosis (CDMS)	14.3; 8.7; 9.0; 26.0; 14.2; 13.7	0.0087 sig
SECONDARY Core Treatment Period: Time to Conversion to Definite Multiple Sclerosis (DMS)	58.2; 45.7; 46.0; 72.4; 57.3; 57.8	0.0003 sig
SECONDARY Core Treatment Period: Annualized Relapse Rate (ARR)	0.284; 0.190; 0.194	—
SECONDARY Core Treatment Period: Brain Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Lesion Volume at Week 108	0.053; 0.041; -0.038	—
SECONDARY Core Treatment Period: Brain MRI Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan (Poisson Regression Estimates)	0.953; 0.749; 0.395	—
SECONDARY Core Treatment Period: Brain MRI Assessment: Volume of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan	0.079; 0.058; 0.034	—
SECONDARY Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of Hypointense Post-Gadolinium T1 Lesion Component	0.028; 0.025; -0.033	—
SECONDARY Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of T2 Lesion Component	0.052; 0.036; -0.035	—
SECONDARY Core Treatment Period: Brain MRI Assessment: Percent Change From Baseline in Atrophy	-0.386; -0.197; -0.366	—
SECONDARY Core Treatment Period: Time to 12-Week Sustained Disability Progression	96.0; 94.3; 97.9; 91.7; 90.1; 93.9	—
SECONDARY Core Treatment Period: Change From Baseline in EDSS at Week 108	0.069; -0.191; -0.166	—
SECONDARY Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 108	-2.537; -2.524; -1.827	—
SECONDARY Core Treatment Period: Overview of Adverse Events (AEs)	155; 161; 183; 18; 18; 24	—
SECONDARY Extension Treatment Period: Time to Conversion to Clinically Deﬁnite Multiple Sclerosis (CDMS)	4.7; 3.5; 13.5; 4.7; 12.5; 9.9	—
SECONDARY Extension Treatment Period: Overview of Adverse Events (AEs)	47; 110; 57; 120; 8; 17	—

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

Eligibility Criteria

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.

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Data sourced from ClinicalTrials.gov (NCT00622700). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.