- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00811395
Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis
Long-term Extension of the Multinational, Double-blind, Placebo Controlled Studies PDY6045 and PDY6046 to Document the Safety of Teriflunomide When Added to Treatment With Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis With Relapses
The primary objective was to evaluate the long-term safety and tolerability of teriflunomide when added to treatment with interferon-β [IFN-β] or glatiramer Acetate [GA] in patients with multiple sclerosis [MS] with relapses.
Secondary objectives were to evaluate the long-term effect on relapse rate, disability progression and Magnetic Resonance Imaging [MRI] parameters.
This study is the extension study of the PDY6045 (NCT00489489) and PDY6046 (NCT00475865) studies. Participants who successfully completed the initial study were offered to continue their treatment (same compound, same dose) for 24 additional weeks.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The duration of the extension study per participants was 40 weeks broken down as follows:
- 24-week double-blind treatment period,
- 16-week post-treatment elimination follow-up period.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Wien, 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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Milano, Italy
- Sanofi-Aventis Administrative Office
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Barcelona, Spain
- 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:
PDY6045 or PDY6046 participant who:
- completed the week 24 visit of either study PDY6045 or PDY6046,
- was still meeting eligibility criteria for receiving treatment,
- had agreed to continue stable dose of Interferon-β [IFN-β] or Glatiramer Acetate [GA] and consented to continue on treatment.
Exclusion Criteria:
- Any known condition or circumstance that would have prevented in the investigator's opinion, compliance or completion of the study
The above information is not intended to contain all considerations relevant to 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 + IFN-β
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
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Film-coated tablet Oral administration
Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection
Other Names:
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EXPERIMENTAL: Teriflunomide 7 mg + IFN-β
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
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Film-coated tablet Oral administration
Other Names:
Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection
Other Names:
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EXPERIMENTAL: Teriflunomide 14 mg + IFN-β
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
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Film-coated tablet Oral administration
Other Names:
Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection
Other Names:
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PLACEBO_COMPARATOR: Placebo + GA
Placebo (for teriflunomide) once daily concomitantly with glatiramer acetate [GA] for 24 additional 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 additional 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 additional 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 in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 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 in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
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Overview of AE With Potential Risk of Occurence
Time Frame: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 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 in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
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Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]
Time Frame: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 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 in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Annualized Relapse Rate [ARR]: Poisson Regression Estimates
Time Frame: 48 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, two Poisson regression models with robust error variance were used (total number of confirmed relapses as response variable, log-transformed treatment duration as "offset" variable and:
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48 weeks
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Overview of 12-week Sustained Disability Progression
Time Frame: 48 weeks
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12-week sustained disability progression was defined as an increase from baseline of at least 1-point in EDSS score (at least 0.5-point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks. If no disability progression was observed on or before last EDSS evaluation before study drug discontinuation, then the participant was considered as free of disability progression. |
48 weeks
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Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints
Time Frame: 48 weeks
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Probability of disability progression at 24 and 48 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase. Participants free of disability progression were censored at the date of the last on-treatment EDSS evaluation. Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t. |
48 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 in PDY6045 or PDY6046) and 48 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 two Mixed-effect models with repeated measures [MMRM] on cubic root transformed volume data:
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baseline (before randomization in PDY6045 or PDY6046) and 48 weeks
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Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
Time Frame: 48 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, two Poisson regression models with robust error variance were used (total number of Gd-enhancing T1-lesions as response variable, log-transformed number of scans as "offset" variable and:
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48 weeks
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Cerebral MRI Assessment: Total Volume of Gd-enhancing T1-lesions Per Scan
Time Frame: 48 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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48 weeks
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Freedman MS, Wolinsky JS, Wamil B, Confavreux C, Comi G, Kappos L, Olsson TP, Miller A, Benzerdjeb H, Li H, Simonson C, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center. Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012 Jun 5;78(23):1877-85. doi: 10.1212/WNL.0b013e318258f7d4. Epub 2012 May 23.
- Freedman MS, Wolinsky JS, Truffinet P, Comi G, Kappos L, Miller AE, Olsson TP, Benamor M, Chambers S, O'Connor PW. A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. Mult Scler J Exp Transl Clin. 2015 Dec 7;1:2055217315618687. doi: 10.1177/2055217315618687. eCollection 2015 Jan-Dec.
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
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
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Adjuvants, Immunologic
- Interferons
- Interferon-beta
- Interferon beta-1b
- Glatiramer Acetate
- (T,G)-A-L
- Teriflunomide
Other Study ID Numbers
- LTS6047
- HMR1726D/2005 (OTHER: HMR)
- 2007-003997-24 (EUDRACT_NUMBER)
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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