MSFrontier

TOPIC

An International, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Two Year Treatment With Teriflunomide 7 mg Once Daily and 14 mg Once Daily Versus Placebo in Patients With a First Clinical Episode Suggestive of Multiple Sclerosis Plus a Long Term Extension Period
CompletedPhase 3Early (CIS/RIS)NCT006227002006-001152-12

What it found

Met its main goal

The main measure showed a statistically significant benefit.

MeasureEstimate95% CIp
Core Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)Hazard Ratio (HR) 0.5740.379–0.8690.0087
Core Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)Hazard Ratio (HR) 0.6280.416–0.9490.0271

Statistical analysis as posted on ClinicalTrials.gov.

What was tested

Treatment tested

Placebo or sham

  • Placebo

Results by group

Core Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)

Up to a maximum of 108 weeks depending on time of enrollment

GroupValueIntervalNumber analysed
Placebo14.3 percent probability9.2–19.4197
Teriflunomide 7 mg8.7 percent probability4.6–12.8203
Teriflunomide 14 mg9.0 percent probability5–13214
Placebo26.0 percent probability19.2–32.8197
Teriflunomide 7 mg14.2 percent probability8.9–19.6203
Teriflunomide 14 mg13.7 percent probability8.6–18.7214
Placebo35.9 percent probability27.8–43.9197
Teriflunomide 7 mg27.6 percent probability19.9–35.4203
Teriflunomide 14 mg24.0 percent probability17–31214

p = 0.0087; Hazard Ratio (HR) 0.574 (95% CI 0.379–0.869)

Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.

Safety

GroupParticipants at riskSerious adverse eventsDeaths
Placebo19118 (9.4%)
Teriflunomide 7 mg20718 (8.7%)
Teriflunomide 14 mg21624 (11.1%)
Placebo/Teriflunomide 7 mg628 (12.9%)
Teriflunomide 7 mg/7 mg14517 (11.7%)
Placebo/Teriflunomide 14 mg668 (12.1%)
Teriflunomide 14 mg/14 mg15024 (16.0%)

As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.

What it measured

Main measures

  • Core Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)

    Up to a maximum of 108 weeks depending on time of enrollment

    Relapses

  • The primary endpoint is efficacy (conversion to clinically definite MS).

Other measures (15)

  • Core Treatment Period: Time to Conversion to Definite Multiple Sclerosis (DMS)

    Up to a maximum of 108 weeks depending on time of enrollment

    Disability progressionRelapsesMRI lesions

  • Core Treatment Period: Annualized Relapse Rate (ARR)

    Up to a maximum of 108 weeks depending on time of enrollment

    Disability progressionRelapses

  • Core Treatment Period: Brain Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Lesion Volume at Week 108

    Baseline, Week 108

    MRI lesions

  • Core Treatment Period: Brain MRI Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan (Poisson Regression Estimates)

    Up to a maximum of 108 weeks depending on time of enrollment

    MRI lesions

  • Core Treatment Period: Brain MRI Assessment: Volume of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan

    Up to a maximum of 108 weeks depending on time of enrollment

    MRI lesions

  • Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of Hypointense Post-Gadolinium T1 Lesion Component

    Baseline, Week 108

    MRI lesions

  • Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of T2 Lesion Component

    Baseline, Week 108

    MRI lesions

  • Core Treatment Period: Brain MRI Assessment: Percent Change From Baseline in Atrophy

    Baseline, Week 108

    MRI lesionsBrain volume loss

  • Core Treatment Period: Time to 12-Week Sustained Disability Progression

    Up to a maximum of 108 weeks depending on time of enrollment

    Disability progression

  • Core Treatment Period: Change From Baseline in EDSS at Week 108

    Baseline, Week 108

    Disability progressionBladder, bowel and sexual function

Who could take part

Early (CIS/RIS) · 18 to 55

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.

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

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

Papers

Loading reviews and guidelines…

Related trials

  • TERIS

    Phase 3 · Completed

    Met its main goal

  • TERICIS

    Phase 3 · Completed

    No result found

  • TERICIS

    Phase 3 · Completed

History

    1. Started

      Feb 2008

    2. Main results due

      Dec 2012

    3. Finished

      Feb 2016

    4. Results posted

      Dec 2014

    Assembled by software from public sources and not checked by people. Each record links to its source. Report an error