- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00475865
Phase II Study of Teriflunomide as Adjunctive Therapy to Glatiramer Acetate in Subjects With Multiple Sclerosis
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Vienna, Austria
- Sanofi-Aventis Administrative Office
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Laval, Canada
- Sanofi-Aventis Administrative Office
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Berlin, Germany
- Sanofi-Aventis Administrative Office
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Milan, Italy
- Sanofi-Aventis Administrative Office
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Guildford, United Kingdom
- Sanofi-Aventis Administrative Office
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New Jersey
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Bridgewater, New Jersey, United States, 08807
- Sanofi-Aventis Administrative Office
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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PLACEBO_COMPARATOR: Placebo + GA
Placebo (for teriflunomide) once daily concomitantly with glatiramer acetate (GA) for 24 weeks
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Film-coated tablet Oral administration
Solution in prefilled syringe for subcutaneous injection
Other Names:
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EXPERIMENTAL: Teriflunomide 7 mg + GA
Teriflunomide 7 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks
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Film-coated tablet Oral administration
Other Names:
Solution in prefilled syringe for subcutaneous injection
Other Names:
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EXPERIMENTAL: Teriflunomide 14 mg + GA
Teriflunomide 14 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks
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Film-coated tablet Oral administration
Other Names:
Solution in prefilled syringe for subcutaneous injection
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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)
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AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
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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)
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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)
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AE with potential risk of occurrence were defined as follows:
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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)
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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)
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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:
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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)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan
Time Frame: 24 weeks
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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.
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24 weeks
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Pharmacokinetic [PK]: Teriflunomide Plasma Concentration
Time Frame: 24 weeks
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Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods.
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24 weeks
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Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
Time Frame: baseline (before randomization) and 24 weeks
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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). |
baseline (before randomization) and 24 weeks
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Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
Time Frame: 24 weeks
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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). |
24 weeks
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Annualized Relapse Rate [ARR]: Poisson Regression Estimates
Time Frame: 24 weeks
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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). |
24 weeks
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Sclerosis
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Adjuvants, Immunologic
- Glatiramer Acetate
- (T,G)-A-L
- Teriflunomide
Other Study ID Numbers
- PDY6046
- 2006-004893-29 (EUDRACT_NUMBER)
- HMR1726D-2004 (OTHER: HMR)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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