Multiple SclerosisPhase 2NCT00489489
Phase II Study of Teriflunomide as Adjunctive Therapy to Interferon-beta in Subjects With Multiple Sclerosis
A Phase 2 study testing Teriflunomide and Interferon-β in people with Multiple Sclerosis, run by Sanofi at 5 sites in 5 countries.
Trial summary
The primary objective was to estimate the tolerability and safety of 2 doses of teriflunomide administered once daily for 24 weeks, compared with placebo, in patients with multiple sclerosis [MS] with relapses who were on a stable dose of interferon-β [IFN-β]. 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 and Interferon-β
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 5 sitesin 5 countries
- Study dates
- May 2007to Jun 2009
- 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
- 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 IFN-β 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
United States1 site
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, 08807
About this study
Official 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 Interferon-beta 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 with placebo, in patients with multiple sclerosis [MS] with relapses who were on a stable dose of interferon-β [IFN-β].
Secondary objectives were:
- to estimate the effects of the 2 doses of teriflunomide, compared to placebo, in combination with a stable dose of IFN-β 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 IFN-β.
Read the detailed description
The study period per 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Teriflunomide, Placebo (for Teriflunomide), Interferon-β
- Keywords
- MS, interferon-beta, adjunctive therapy, relapses
- Medical subject headings
- Multiple Sclerosis, Recurrence
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-βDrug
Also called Avonex®, Rebif®, Betaseron®
Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Teriflunomide 7 mg + IFN-β | Experimental | Teriflunomide 7 mg once daily concomitantly with Interferon-β (IFN-β) for 24 weeks Receives: Drug: Teriflunomide; Drug: Interferon-β |
| Teriflunomide 14 mg + IFN-β | Experimental | Teriflunomide 14 mg once daily concomitantly with Interferon-β (IFN-β) for 24 weeks Receives: Drug: Teriflunomide; Drug: Interferon-β |
| Placebo + IFN-β | Placebo comparator | Placebo (for Teriflunomide) once daily concomitantly with Interferon-β (IFN-β) for 24 weeks Receives: Drug: Placebo (for Teriflunomide); Drug: Interferon-β |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
Overview of AE With Potential Risk of Occurrence
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 up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
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 up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
Secondary outcomes (5)
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 of 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, IFN-β dose level, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors).
Measured: baseline (before randomization) and 24 weeks
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, 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, IFN-β dose level and baseline number of Gd-enhancing T1-lesions as covariates).
Measured: 24 weeks
Cerebral MRI Assessment: 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: 24 weeks
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, 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, region of enrollment and IFN-β dose level as covariates).
Measured: 24 weeks
Pharmacokinetic [PK]: Teriflunomide Plasma Concentration
Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2007 (estimated)
- Study startMay 2007
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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, Investigator, Outcomes assessor
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ICD, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00489489
- Sponsor's protocol ID
- PDY6045
- Other IDs
- 2006-003134-14, HMR1726D-2003
- Status last verified
- Nov 2012
- First submitted
- 20 Jun 2007
- Last updated
- 6 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- 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
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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 Interferon-beta in Subjects With Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT00489489
- Acronym / sponsor ID
- PDY6045
- Conditions
- Multiple Sclerosis
- Keywords
- MS, interferon-beta, adjunctive therapy, relapses
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 21 Jun 2007 (estimated)
- Results
- Posted 2 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective was to estimate the tolerability and safety of 2 doses of teriflunomide administered once daily for 24 weeks, compared with placebo, in patients with multiple sclerosis [MS] with relapses who were on a stable dose of interferon-β [IFN-β].
Secondary objectives were:
- to estimate the effects of the 2 doses of teriflunomide, compared to placebo, in combination with a stable dose of IFN-β 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 IFN-β.
Detailed description
The study period per 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Teriflunomide 7 mg + IFN-β | Experimental | Drug: Teriflunomide, Drug: Interferon-βTeriflunomide 7 mg once daily concomitantly with Interferon-β (IFN-β) for 24 weeks |
| Teriflunomide 14 mg + IFN-β | Experimental | Drug: Teriflunomide, Drug: Interferon-βTeriflunomide 14 mg once daily concomitantly with Interferon-β (IFN-β) for 24 weeks |
| Placebo + IFN-β | Placebo comparator | Drug: Placebo (for Teriflunomide), Drug: Interferon-βPlacebo (for Teriflunomide) once daily concomitantly with Interferon-β (IFN-β) for 24 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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 IFN-β for at least 26 weeks prior to the screening visit;
- No onset of MS relapse in the preceding 60 days prior to randomization;
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TeriflunomideAlso: HMR1726Film-coated tablet Oral administration | Drug | Teriflunomide 14 mg + IFN-β, Teriflunomide 7 mg + IFN-β |
| Placebo (for Teriflunomide)Film-coated tablet Oral administration | Drug | Placebo + IFN-β |
| Interferon-βAlso: Avonex®, Rebif®, Betaseron®Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection | Drug | Placebo + IFN-β, Teriflunomide 14 mg + IFN-β, Teriflunomide 7 mg + IFN-β |
Primary outcome
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.
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.
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;
5 secondary outcomes
Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
Time frame: baseline (before randomization) and 24 weeks
Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
Time frame: 24 weeks
Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan
Time frame: 24 weeks
Annualized Relapse Rate [ARR]: Poisson Regression Estimates
Time frame: 24 weeks
Pharmacokinetic [PK]: Teriflunomide Plasma Concentration
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22622860Freedman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ICD study director
Sanofi
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Teriflunomide and Interferon-β in people with Multiple Sclerosis, run by Sanofi at 5 sites in 5 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 6 inclusion and 7 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 6 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada, Germany, Italy, Spain. 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 2 Nov 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 up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 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 NCT00489489, which also lists 1 linked publication.
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 6 Nov 2012.