Back to resultsSafety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Teriflunomide
Placebo (placebo for teriflunomide)
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Clinically confirmed multiple sclerosis [MS];
- Expanded Disability Status Scale [EDSS] score less or equal to 6;
- Two documented relapses in the previous 3 years, and one clinical relapse during the preceding year;
- Screening magnetic resonance imaging [MRI] scan fulfilling the criteria for a diagnosis of MS.
Exclusion Criteria:
- Clinically relevant cardiovascular, hepatic, hematologic, neurological, endocrine or other major systemic disease;
- Pregnant or nursing woman;
- Wish to parent children during the trial or following the trial (men and women were required to practice effective contraception during the trial and for 24 months after drug discontinuation);
- Prior treatment with interferon [IFN], gamma-globulin, glatiramer acetate, or other noncorticosteroid immunomodulatory therapies in the 4 months prior to the trial;
- Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment;
- 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.
Sites / Locations
- Canada
- sanofi-aventis France
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Teriflunomide 7 mg
Teriflunomide 14 mg
Arm Description
Placebo (for teriflunomide), two tablets once daily for 1 week then, one tablet once daily for 35 weeks.
Teriflunomide 7 mg: two tablets once daily for 1 week then, one tablet once daily for 35 weeks.
Teriflunomide 14 mg: two tablets once daily for 1 week then, one tablet once daily for 35 weeks.
Outcomes
Primary Outcome Measures
MRI assessment: number of unique active lesions per scan (T2/proton density and gadolinium-enhanced T1 scan analysis)
The number of unique active lesions per scan was calculated by dividing the sum of unique newly active lesions and unique persistently active lesions observed on treatment by the number of scans performed on treatment.
Unique newly active lesions were all unique T1 and T2 lesions identified, one or more times, in a scan but not in the previous scan and, that had not been classified as unique newly active in any previous scan.
Unique persistently active lesions were all unique T1 and T2 lesions identified, one or more times, in a scan and also in the previous scan.
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.
Secondary Outcome Measures
MRI assessment: number of T1-enhancing lesions per scan
T1-enhancing lesions included:
Newly enhancing T1 lesions: lesions enhanced on the current T1 scan but not enhanced in any previous T1 scan.
Persistently enhancing T1 lesions: lesions enhanced on the current T1 scan and enhanced on the previous T1 scan.
MRI assessment: number of T2-lesions per scan
T2-lesions included:
New T2-lesions: lesions that appeared on the current T2 scan but were not visible on any previous T2 scans.
Newly enlarging T2-lesions: lesions that appeared enlarged on the current T2 scan but were stable on the previous T2 scan.
Persistently enlarging T2-lesions: further enlarged lesions on the current T2 scan categorized as new or enlarging on the previous T2 scan.
MRI assessment: Number of participants with no new lesions
New lesions included new T2 lesions, new enhanced T1 lesions and unique newly active lesions.
MRI assessment: Change from baseline in T2 burden of disease
T2 burden of disease was defined as the total volume of all T2 lesions.
Number of participants with progression on Expanded Disability Status Scale [EDSS]
EDSS is an ordinal scale in half-point increments that qualifies disability in patients with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation.
EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS).
Progression was defined as an increase in EDSS score by at least 1-point when baseline EDSS score ≤5.5 or an increase in EDSS score by at least 0.5-point in when baseline EDSS score >5.5.
Number of participants with MS relapse confirmed by Scripps Neurological Rating Scale [NRS] and EDSS scores.
A relapse was defined as the appearance, reappearance or worsening of a symptom attributable to MS. The change had to persist for at least 48 hours in the absence of fever and be preceded by stability or improvement for at least 30 days. Relapses were to be confirmed by Scripps NRS and EDSS scores.
NRS is a scale that qualifies the degree of impairment from a neurological exam of the following systems: mentation and mood, cranial nerves, motor nerves, deep tendon reflexes, sensory nerves, cerebellum, gait/trunk/balance, bladder/bowel/sexual dysfunction.
NRS score ranges from 0 to 100 (lower degree of impairment).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01487096
Brief Title
Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Official Title
A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
April 2001 (undefined)
Primary Completion Date
March 2003 (Actual)
Study Completion Date
March 2003 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study was to determine the safety and efficacy of teriflunomide in multiple sclerosis (MS) with relapses.
Secondary objectives were:
To determine the effect of teriflunomide on additional magnetic resonance imaging (MRI) variables as well as clinical and quality of life measures.
To investigate the pharmacokinetic and pharmacodynamic relationships.
Detailed Description
The total duration of the study period per participants was 46 weeks comprising 3 periods:
a 4-week screening period,
a 36-week double-blind treatment period,
a 6-week post-treatment follow-up period.
Participants who successfully completed the double-blind treatment phase were offered the possibility to continue study treatment in the extension study LTS6048 - NCT00228163.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
179 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (for teriflunomide),
two tablets once daily for 1 week then,
one tablet once daily for 35 weeks.
Arm Title
Teriflunomide 7 mg
Arm Type
Experimental
Arm Description
Teriflunomide 7 mg:
two tablets once daily for 1 week then,
one tablet once daily for 35 weeks.
Arm Title
Teriflunomide 14 mg
Arm Type
Experimental
Arm Description
Teriflunomide 14 mg:
two tablets once daily for 1 week then,
one tablet once daily for 35 weeks.
Intervention Type
Drug
Intervention Name(s)
Teriflunomide
Other Intervention Name(s)
HMR1726
Intervention Description
film-coated tablet
oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo (placebo for teriflunomide)
Intervention Description
film-coated tablet
oral administration
Primary Outcome Measure Information:
Title
MRI assessment: number of unique active lesions per scan (T2/proton density and gadolinium-enhanced T1 scan analysis)
Description
The number of unique active lesions per scan was calculated by dividing the sum of unique newly active lesions and unique persistently active lesions observed on treatment by the number of scans performed on treatment.
Unique newly active lesions were all unique T1 and T2 lesions identified, one or more times, in a scan but not in the previous scan and, that had not been classified as unique newly active in any previous scan.
Unique persistently active lesions were all unique T1 and T2 lesions identified, one or more times, in a scan and also in the previous scan.
Time Frame
36 weeks
Title
Overview of Adverse Events [AE]
Description
AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time Frame
from first study drug intake up to 6 weeks after last intake or entry in the extension study, whichever came first
Secondary Outcome Measure Information:
Title
MRI assessment: number of T1-enhancing lesions per scan
Description
T1-enhancing lesions included:
Newly enhancing T1 lesions: lesions enhanced on the current T1 scan but not enhanced in any previous T1 scan.
Persistently enhancing T1 lesions: lesions enhanced on the current T1 scan and enhanced on the previous T1 scan.
Time Frame
36 weeks
Title
MRI assessment: number of T2-lesions per scan
Description
T2-lesions included:
New T2-lesions: lesions that appeared on the current T2 scan but were not visible on any previous T2 scans.
Newly enlarging T2-lesions: lesions that appeared enlarged on the current T2 scan but were stable on the previous T2 scan.
Persistently enlarging T2-lesions: further enlarged lesions on the current T2 scan categorized as new or enlarging on the previous T2 scan.
Time Frame
36 weeks
Title
MRI assessment: Number of participants with no new lesions
Description
New lesions included new T2 lesions, new enhanced T1 lesions and unique newly active lesions.
Time Frame
36 weeks
Title
MRI assessment: Change from baseline in T2 burden of disease
Description
T2 burden of disease was defined as the total volume of all T2 lesions.
Time Frame
36 weeks
Title
Number of participants with progression on Expanded Disability Status Scale [EDSS]
Description
EDSS is an ordinal scale in half-point increments that qualifies disability in patients with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation.
EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS).
Progression was defined as an increase in EDSS score by at least 1-point when baseline EDSS score ≤5.5 or an increase in EDSS score by at least 0.5-point in when baseline EDSS score >5.5.
Time Frame
36 weeks
Title
Number of participants with MS relapse confirmed by Scripps Neurological Rating Scale [NRS] and EDSS scores.
Description
A relapse was defined as the appearance, reappearance or worsening of a symptom attributable to MS. The change had to persist for at least 48 hours in the absence of fever and be preceded by stability or improvement for at least 30 days. Relapses were to be confirmed by Scripps NRS and EDSS scores.
NRS is a scale that qualifies the degree of impairment from a neurological exam of the following systems: mentation and mood, cranial nerves, motor nerves, deep tendon reflexes, sensory nerves, cerebellum, gait/trunk/balance, bladder/bowel/sexual dysfunction.
NRS score ranges from 0 to 100 (lower degree of impairment).
Time Frame
36 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinically confirmed multiple sclerosis [MS];
Expanded Disability Status Scale [EDSS] score less or equal to 6;
Two documented relapses in the previous 3 years, and one clinical relapse during the preceding year;
Screening magnetic resonance imaging [MRI] scan fulfilling the criteria for a diagnosis of MS.
Exclusion Criteria:
Clinically relevant cardiovascular, hepatic, hematologic, neurological, endocrine or other major systemic disease;
Pregnant or nursing woman;
Wish to parent children during the trial or following the trial (men and women were required to practice effective contraception during the trial and for 24 months after drug discontinuation);
Prior treatment with interferon [IFN], gamma-globulin, glatiramer acetate, or other noncorticosteroid immunomodulatory therapies in the 4 months prior to the trial;
Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment;
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Study Director
Organizational Affiliation
Clinical Science & Operation - sanofi-aventis
Official's Role
Study Director
Facility Information:
Facility Name
Canada
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
sanofi-aventis France
City
Lyon
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
16567708
Citation
O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R; Teriflunomide Multiple Sclerosis Trial Group; University of British Columbia MS/MRI Research Group. A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology. 2006 Mar 28;66(6):894-900. doi: 10.1212/01.wnl.0000203121.04509.31.
Results Reference
result
PubMed Identifier
33023488
Citation
Comi G, Freedman MS, Meca-Lallana JE, Vermersch P, Kim BJ, Parajeles A, Edwards KR, Gold R, Korideck H, Chavin J, Poole EM, Coyle PK. Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis. BMC Neurol. 2020 Oct 6;20(1):364. doi: 10.1186/s12883-020-01937-4.
Results Reference
derived
Learn more about this trial
Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
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