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Trial record 8 of 20 for:    teriflunomide

Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00811395
First received: December 18, 2008
Last updated: December 18, 2012
Last verified: December 2012

December 18, 2008
December 18, 2012
October 2007
April 2010   (final data collection date for primary outcome measure)
  • 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) ] [ Designated as safety issue: Yes ]
    AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
  • 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) ] [ Designated as safety issue: Yes ]

    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.
  • 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) ] [ Designated as safety issue: Yes ]

    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;
Safety: adverse events, laboratory parameters, ECG, CT or MRI images of pancreas, and vital signs [ Time Frame: study period ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00811395 on ClinicalTrials.gov Archive Site
  • Annualized Relapse Rate [ARR]: Poisson Regression Estimates [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    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:

    • Model 1 (IFN-β groups): treatment group, region of enrollment and IFN-β dose level as covariates
    • Model 2 (GA groups): treatment group and region of enrollment as covariates)
  • Overview of 12-week Sustained Disability Progression [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    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.

  • Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    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.

  • 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 ] [ Designated as safety issue: No ]

    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:

    • Model 1 (IFN-β groups): treatment group, region of enrollment, IFN-β dose level, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors;
    • Model 2 (GA groups): treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors.
  • Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    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:

    • Model 1 (IFN-β groups): Treatment group, region of enrollment, IFN-β dose level and baseline number of Gd-enhancing T1-lesions as covariates
    • Model 2 (GA groups): Treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates)
  • Cerebral MRI Assessment: Total Volume of Gd-enhancing T1-lesions Per Scan [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    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.
  • Annualized MS relapse rate [ Time Frame: study period ] [ Designated as safety issue: No ]
  • Time to disability progression [ Time Frame: study period ] [ Designated as safety issue: No ]
  • MRI variables [ Time Frame: study period ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Multiple Sclerosis
  • Drug: Teriflunomide

    Film-coated tablet

    Oral administration

    Other Name: HMR1726
  • Drug: Placebo (for teriflunomide)

    Film-coated tablet

    Oral administration

  • Drug: Interferon-β [IFN-β]
    Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection
    Other Names:
    • Avonex®
    • Rebif®
    • Betaseron®
  • Drug: Glatiramer Acetate [GA]
    Solution in prefilled syringe for subcutaneous injection
    Other Name: Copaxone®
  • Placebo Comparator: Placebo + IFN-β
    Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
    Interventions:
    • Drug: Placebo (for teriflunomide)
    • Drug: Interferon-β [IFN-β]
  • Experimental: Teriflunomide 7 mg + IFN-β
    Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
    Interventions:
    • Drug: Teriflunomide
    • Drug: Interferon-β [IFN-β]
  • Experimental: Teriflunomide 14 mg + IFN-β
    Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
    Interventions:
    • Drug: Teriflunomide
    • Drug: Interferon-β [IFN-β]
  • Placebo Comparator: Placebo + GA
    Placebo (for teriflunomide) once daily concomitantly with glatiramer acetate [GA] for 24 additional weeks
    Interventions:
    • Drug: Placebo (for teriflunomide)
    • Drug: Glatiramer Acetate [GA]
  • Experimental: Teriflunomide 7 mg + GA
    Teriflunomide 7 mg once daily concomitantly with glatiramer acetate [GA] for 24 additional weeks
    Interventions:
    • Drug: Teriflunomide
    • Drug: Glatiramer Acetate [GA]
  • Experimental: Teriflunomide 14 mg + GA
    Teriflunomide 14 mg once daily concomitantly with glatiramer acetate [GA] for 24 additional weeks
    Interventions:
    • Drug: Teriflunomide
    • Drug: Glatiramer Acetate [GA]
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-β 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
182
April 2010
April 2010   (final data collection date for primary outcome measure)

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.

Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   Canada,   Germany,   Italy,   Spain,   United Kingdom
 
NCT00811395
LTS6047, HMR1726D/2005, 2007-003997-24
Yes
Sanofi
Sanofi
Not Provided
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP