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

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Multiple Sclerosis Relapse

Treatments: Drug: Placebo (for teriflunomide); Drug: Interferon-beta (IFN-beta); Drug: Teriflunomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01252355

2010-023172-12 (EudraCT Number)

EFC6058

U1111-1115-2414 (Other Identifier)

Details and patient eligibility

About

The primary objective was to demonstrate 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-beta).

The secondary objectives were:

• Assess the effect of teriflunomide, in comparison to placebo, when added to IFN-beta 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-beta therapy

• Assess the pharmacokinetics of teriflunomide in use in addition to baseline IFN-beta 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 intensive care unit)

Full description

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

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

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

For those patients who completed the treatment period, a long term extension study of approximately 1 year (including teriflunomide alone) was initially planned to be proposed.

Enrollment: 534 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Patient with relapsing forms of MS treated with IFN-beta
• Stable dose of IFN-beta (approved brand) for at least 6 months prior to randomization
• Disease activity in the 12 months prior to randomization and after first 3 months of IFN-beta treatment (defined by at least 1 relapse supported by EDSS or equivalent neurological examination, or, at least 1 brain or spinal cord MRI with at least one T1 gadolinium enhancing lesion)

Exclusion criteria:

• McDonald criteria for MS diagnosis not met at time of screening visit
• EDSS score greater than (>) 5.5 at randomization visit
• A relapse within 30 days prior randomization
• Persistent significant or severe infection
• Patients must not have used adrenocorticotrophic hormone or systemic corticosteroids for 2 weeks prior to randomization
• Prior or concomitant use of cytokine therapy (except baseline interferons), glatiramer acetate or intravenous immunoglobulins in the 3 months preceding randomization
• Liver function impairment or persisting elevations (confirmed by retest) of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or direct bilirubin greater than 2 times the upper limit of normal range (ULN)
• Active hepatitis or hepatobiliary disease or known history of severe hepatitis
• Pregnant or breast-feeding women or those who were planning to become pregnant during the study
• Significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia
• Human Immunodeficiency Virus (HIV) positive
• Known history of active tuberculosis not adequately treated
• Prior use within 2 years preceding randomization or concomitant use of cladribine and mitoxantrone
• 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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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534 participants in 3 patient groups, including a placebo group

Teriflunomide 7 mg + IFN-beta

Experimental group

Description:

Teriflunomide 7 milligram (mg) once a day concomitantly with IFN-beta therapy.

Treatment:

Drug: Teriflunomide

Drug: Interferon-beta (IFN-beta)

Teriflunomide 14 mg + IFN-beta

Experimental group

Description:

Teriflunomide 14 mg once a day concomitantly with IFN-beta therapy.

Treatment:

Drug: Teriflunomide

Drug: Interferon-beta (IFN-beta)

Placebo + IFN-beta

Placebo Comparator group

Description:

Placebo (for teriflunomide) once a day concomitantly with IFN-beta therapy.

Treatment:

Drug: Placebo (for teriflunomide)

Drug: Interferon-beta (IFN-beta)