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Multiple SclerosisPhase 2NCT00811395

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

A Phase 2 study testing Teriflunomide, Interferon-β [IFN-β] and Glatiramer Acetate [GA] in people with Multiple Sclerosis, run by Sanofi at 7 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Teriflunomide, Interferon-β [IFN-β] and Glatiramer Acetate [GA]
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
182 participants
Where
7 sitesin 7 countries
Study dates
Oct 2007to Apr 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

7 sites in 7 countries.

7 sites in 7 countries

United States1 site
  • Sanofi-Aventis Administrative Office

    Bridgewater, New Jersey, 08807

Other trials in United States

Austria1 site
  • Sanofi-Aventis Administrative Office

    Vienna

Other trials in Austria

Canada1 site
  • Sanofi-Aventis Administrative Office

    Laval

Other trials in Canada

Germany1 site
  • Sanofi-Aventis Administrative Office

    Berlin

Other trials in Germany

Italy1 site
  • Sanofi-Aventis Administrative Office

    Milan

Other trials in Italy

Spain1 site
  • Sanofi-Aventis Administrative Office

    Barcelona

Other trials in Spain

United Kingdom1 site
  • Sanofi-Aventis Administrative Office

    Guildford

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.
Being tested
Teriflunomide, Placebo (for teriflunomide), Interferon-β [IFN-β], Glatiramer Acetate [GA]
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TeriflunomideDrug

    Also called HMR1726

    Film-coated tablet

    Oral administration

  • Placebo (for teriflunomide)Drug

    Film-coated tablet

    Oral administration

  • Interferon-β [IFN-β]Drug

    Also called Avonex®, Rebif®, Betaseron®

    Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection

  • Glatiramer Acetate [GA]Drug

    Also called Copaxone®

    Solution in prefilled syringe for subcutaneous injection

Study groups in NCT00811395
Study groupRoleWhat they receive
Placebo + IFN-βPlacebo comparatorPlacebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
Receives: Drug: Placebo (for teriflunomide); Drug: Interferon-β [IFN-β]
Teriflunomide 7 mg + IFN-βExperimentalTeriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
Receives: Drug: Teriflunomide; Drug: Interferon-β [IFN-β]
Teriflunomide 14 mg + IFN-βExperimentalTeriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β] for 24 additional weeks
Receives: Drug: Teriflunomide; Drug: Interferon-β [IFN-β]
Placebo + GAPlacebo comparatorPlacebo (for teriflunomide) once daily concomitantly with glatiramer acetate [GA] for 24 additional weeks
Receives: Drug: Placebo (for teriflunomide); Drug: Glatiramer Acetate [GA]
Teriflunomide 7 mg + GAExperimentalTeriflunomide 7 mg once daily concomitantly with glatiramer acetate [GA] for 24 additional weeks
Receives: Drug: Teriflunomide; Drug: Glatiramer Acetate [GA]
Teriflunomide 14 mg + GAExperimentalTeriflunomide 14 mg once daily concomitantly with glatiramer acetate [GA] for 24 additional weeks
Receives: Drug: Teriflunomide; Drug: Glatiramer Acetate [GA]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overview of Adverse Events [AE]

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

    Measured: 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)

  2. Overview of AE With Potential Risk of Occurence

    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.

    Measured: 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)

  3. Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]

    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;

    Measured: 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)

Secondary outcomes (6)
  1. Annualized Relapse Rate [ARR]: Poisson Regression Estimates

    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)

    Measured: 48 weeks

  2. Overview of 12-week Sustained Disability Progression

    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.

    Measured: 48 weeks

  3. Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints

    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.

    Measured: 48 weeks

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

    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.

    Measured: baseline (before randomization in PDY6045 or PDY6046) and 48 weeks

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

    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)

    Measured: 48 weeks

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

    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.

    Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2008 (estimated)
  2. Study startOct 2007
  3. Primary completionApr 2010
  4. Study completionApr 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
182 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00811395
Sponsor's protocol ID
LTS6047
Other IDs
HMR1726D/2005, 2007-003997-24
Status last verified
Dec 2012
First submitted
18 Dec 2008
Last updated
31 Dec 2012
Data monitoring committee
Yes

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.

    PubMed 22622860
  • 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.

    PubMed 28607708

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Teriflunomide, Interferon-β [IFN-β] and Glatiramer Acetate [GA] in people with Multiple Sclerosis, run by Sanofi at 7 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Austria, Canada, Germany, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00811395, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2012.

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