Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis and Treated With Interferon-beta (TERACLES)

This study has been terminated.
(Sponsor decision to prematurely stop the study, not linked to any safety concern.)
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01252355
First received: November 30, 2010
Last updated: June 6, 2013
Last verified: May 2013
  Purpose

Primary Objective:

Assess the effect of Teriflunomide in comparison to placebo on frequency of Multiple Sclerosis (MS) relapses in patients with relapsing forms of MS who are treated with interferon beta (IFN-β).

Secondary Objectives:

  • Assess the effect of Teriflunomide in comparison to placebo when added to interferon beta (IFN-β) on:

    • Disease activity as measured by brain Magnetic Resonance Imaging (MRI),
    • Disability progression,
    • Burden of disease and disease progression as measured by brain MRI.
  • Evaluate the safety and tolerability of Teriflunomide when added to IFN-β therapy.
  • Assess the pharmacokinetics of Teriflunomide in use in addition to baseline IFN-β therapy.
  • Assess associations between variations in genes and clinical outcomes (safety and efficacy).
  • Assess other measures of efficacy of Teriflunomide such as fatigue and health-related quality of life.
  • Assess measures of health economics (hospitalization due to relapse, including the length of stay and any admission to ICU).

Condition Intervention Phase
Multiple Sclerosis Relapse
Drug: Teriflunomide (HMR1726)
Drug: Matching placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Multi-center Double-blind Parallel-group Placebo-controlled Study of the Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis Who Are Treated With Interferon-beta

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Annualized relapse rate (number of confirmed relapses per patient-year) [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Gadolinium (Gd)-enhancing T1-lesions as measured by brain MRI [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]
  • Time to disability progression as assessed by Expanded Disability Status Scale (EDSS) [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]
  • Burden of disease (Change from baseline in the volume of abnormal brain tissue) and other MRI variables [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]
  • Time to first confirmed relapse [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]
  • Proportion of patients relapse-free [ Time Frame: 1 year, 2 years, and 3 years ] [ Designated as safety issue: No ]
  • Subject reported fatigue as assessed by the Fatigue Impact Scale (FIS) [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]
  • Short Form generic health survey [36 items] (SF-36) score [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]
  • Hospitalization due to relapse, including the length of stay and any admission to ICU [ Time Frame: Average of 2 years (between 1 and 3 years) ] [ Designated as safety issue: No ]

Enrollment: 1455
Study Start Date: January 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Teriflunomide 7 mg
Teriflunomide 7 mg once a day concomitantly with Interferon beta (IFN-β) therapy
Drug: Teriflunomide (HMR1726)

Pharmaceutical form: film-coated tablet

Route of administration: oral

Experimental: Teriflunomide 14 mg
Teriflunomide 14 mg once a day concomitantly with Interferon beta (IFN-β) therapy - Type: Experimental
Drug: Teriflunomide (HMR1726)

Pharmaceutical form: film-coated tablet

Route of administration: oral

Placebo Comparator: Placebo
Matching placebo once a day concomitantly with Interferon beta (IFN-β) therapy
Drug: Matching placebo

Pharmaceutical form: film-coated tablet

Route of administration: oral


Detailed Description:

The study period per patient is expected to be between 56 and 160 weeks depending on when the patient is randomized and this would include the following:

  • a screening period up to 4 weeks,
  • a treatment period expected to be between 48 and 152 weeks,
  • 4-week post washout follow-up period.

Patients will continue on treatment until a fixed common end date which will be approximately 48 weeks after randomization of the last patient.

For those patients who complete the treatment period, a long term extension study of approximately 1 year (including Teriflunomide alone) is planned to be proposed.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

Patient with relapsing forms of multiple sclerosis (MS) treated with Interferon beta (IFN-β) defined by:

  • Stable dose of IFN-β for at least 6 months prior to randomization, and
  • Disease activity in the 12 months prior to randomization and after first 3 months of IFN-β treatment (at least one relapse supported by Expanded Disability status Scale (EDSS) or equivalent neurological examination, or, at least one brain or spinal cord Magnetic Resonance Imaging (MRI) with at least one T1 gadolinium enhancing lesion).

Exclusion criteria:

  • < 18 years of age or ≥ 56 years of age.
  • McDonald criteria for MS diagnosis not met at time of screening visit.
  • EDSS score > 5.5 at randomization visits.
  • A relapse within 30 days prior randomization.
  • Human Immunodeficiency Virus (HIV) positive patient.
  • Prior use within 6 months preceding randomization or concomitant use of natalizumab or any other immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, methotrexate, mycophenolate, or fingolimod.
  • Prior use in the 3 months preceding randomization of cytokine therapy (except baseline IFN-β), glatiramer acetate or intravenous immunoglobulins, or concomitant use of these treatments.
  • Prior use within 2 years preceding randomization or concomitant use of cladribine and mitoxantrone.
  • Pregnant or breast-feeding women or those who plan to become pregnant during the study.

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01252355

  Show 193 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01252355     History of Changes
Other Study ID Numbers: EFC6058, 2010-023172-12, U1111-1115-2414
Study First Received: November 30, 2010
Last Updated: June 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 16, 2014