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Completed

NCT Number: NCT00475865

Phase II Study of Teriflunomide as Adjunctive Therapy to Glatiramer Acetate in Subjects With Multiple Sclerosis

The primary objective was to estimate the tolerability and safety of 2 doses of Teriflunomide administered once daily for 24 weeks, compared to placebo, in patients with multiple sclerosis [MS] with relapses who were on a stable dose of Glatiramer Acetate [GA].

The secondary objectives were:

* to estimate the effect of the 2 doses of Teriflunomide, compared to placebo, in combination with a stable dose of GA on Magnetic Resonance Imaging [MRI] parameters, relapse rate and patient-reported fatigue; * to perform pharmacokinetic analyses of the 2 doses of teriflunomide in combination with a stable dose of GA.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Disease Attributes Immune System Diseases Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sanofi-Aventis Administrative Office, Vienna, Austria

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About this study

The duration of the study period for a participant was approximatively 44 weeks broken down as follows:

  • Screening period up to 4 weeks,
  • 24-week double-blind treatment period*,
  • 16-week post-treatment elimination follow-up period.

'*' Participants successfully completing the week 24 visit were offered the opportunity to enter the optional long-term extension study LTS6047 - NCT00811395.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Definite MS diagnosis according to McDonald's criteria;
  • Relapsing clinical course, with or without progression;
  • Expanded Disability Status Scale [EDSS] less or equal to 5.5 (ambulatory);
  • Stable dose of Glatiramer Acetate [GA] for at least 26 weeks prior to the screening visit;
  • No onset of MS relapse in the preceding 60 days prior to randomization;
  • Clinically stable for 4 weeks prior to randomization.

Exclusion criteria

  • Other chronic disease of the immune system, liver function impairment or chronic pancreatic disease;
  • Pregnant or nursing woman;
  • Alcohol or drug abuse;
  • Use of cladribine, Mitoxantrone, or other immunosuppressant agents such as Azathioprine, Cyclophosphamide, Cyclosporin, Methotrexate or Mycophenolate before enrollment;
  • Human immunodeficiency virus [HIV] positive status;
  • 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 patient's potential participation in a clinical trial.

Treatment and study plan

Teriflunomide

Drug

Film-coated tablet

Oral administration

Other names: HMR1726

Placebo (for teriflunomide)

Drug

Film-coated tablet

Oral administration

Glatiramer Acetate (GA)

Drug

Solution in prefilled syringe for subcutaneous injection

Other names: Copaxone®

Primary outcomes

  1. Overview of Adverse Events (AE]

    Time frame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)

    AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

  2. Overview of AE With Potential Risk of Occurrence

    Time frame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)

    AE with potential risk of occurrence were defined as follows:

    • Hepatic disorders;
    • Immune effects, mainly effects on bone marrow and infection;
    • Pancreatic disorders;
    • Malignancy;
    • Skin disorders, mainly hair loss and hair thinning;
    • Pulmonary disorders;
    • Hypertension;
    • Peripheral neuropathy;
    • Psychiatric disorders;
    • Hypersensitivity.

  3. Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)

    Time frame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)

    PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.

    Hepatic parameters thresholds were defined as follows:

    • Alanine Aminotransferase [ALT] >3, 5, 10 or 20 Upper Normal Limit [ULN];
    • Aspartate aminotransferase [AST] >3, 5, 10 or 20 ULN;
    • Alkaline Phosphatase >1.5 ULN;
    • Total Bilirubin [TB] >1.5 or 2 ULN;
    • ALT >3 ULN and TB >2 ULN.

Secondary outcomes

  1. Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)

    Time frame: baseline (before randomization) and 24 weeks

    Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis.

    Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on cubic root transformed volume data (treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors).

  2. Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)

    Time frame: 24 weeks

    Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.

    To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as "offset" variable; treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates).

  3. Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan

    Time frame: 24 weeks

    Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.

  4. Annualized Relapse Rate [ARR]: Poisson Regression Estimates

    Time frame: 24 weeks

    ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.

    Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores.

    To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group and region of enrollment as covariates).

  5. Pharmacokinetic [PK]: Teriflunomide Plasma Concentration

    Time frame: 24 weeks

    Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods.

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Registry information

Official study title

A Randomized, Multinational, Double-blind, Placebo-controlled, Parallel-group Design Pilot Study to Estimate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamic Effects of Teriflunomide for 24 Weeks When Added to Treatment With Glatiramer Acetate in Subjects With Multiple Sclerosis

Important dates

Study start
2007
Primary completion
2009
Study completion
2009
First posted
May 21, 2007
Registry last updated
Nov 6, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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