Multiple SclerosisPhase 2NCT01487096
Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
A Phase 2 study testing Teriflunomide in people with Multiple Sclerosis, run by Sanofi at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Teriflunomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 179 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Apr 2001to Mar 2003
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
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.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Teriflunomide, Placebo (placebo for teriflunomide)
- 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 (placebo for teriflunomide)Drug
film-coated tablet
oral administration
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo (for teriflunomide),
* two tablets once daily for 1 week then,
* one tablet once daily for 35 weeks. Receives: Drug: Placebo (placebo for teriflunomide) |
| Teriflunomide 7 mg | Experimental | Teriflunomide 7 mg:
* two tablets once daily for 1 week then,
* one tablet once daily for 35 weeks. Receives: Drug: Teriflunomide |
| Teriflunomide 14 mg | Experimental | Teriflunomide 14 mg:
* two tablets once daily for 1 week then,
* one tablet once daily for 35 weeks. Receives: Drug: Teriflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 36 weeks
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 6 weeks after last intake or entry in the extension study, whichever came first
Secondary outcomes (6)
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.
Measured: 36 weeks
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.
Measured: 36 weeks
MRI assessment: Number of participants with no new lesions
New lesions included new T2 lesions, new enhanced T1 lesions and unique newly active lesions.
Measured: 36 weeks
MRI assessment: Change from baseline in T2 burden of disease
T2 burden of disease was defined as the total volume of all T2 lesions.
Measured: 36 weeks
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.
Measured: 36 weeks
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).
Measured: 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2011 (estimated)
- Study startApr 2001
- Primary completionMar 2003
- Study completionMar 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 179 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Study Director, Study director, Clinical Science & Operation - sanofi-aventis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01487096
- Sponsor's protocol ID
- HMR1726D/2001
- Status last verified
- Oct 2012
- First submitted
- 5 Dec 2011
- Last updated
- 4 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16567708Comi 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.
PubMed 33023488
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
- ClinicalTrials.gov ID
- NCT01487096
- Acronym / sponsor ID
- HMR1726D/2001
- Conditions
- Multiple Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 179 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Apr 2001
- Primary completion
- Mar 2003 (actual)
- Study completion
- Mar 2003 (actual)
- First posted
- 7 Dec 2011 (estimated)
- Results
- Not posted in the source record
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo (placebo for teriflunomide)Placebo (for teriflunomide), * two tablets once daily for 1 week then, * one tablet once daily for 35 weeks. |
| Teriflunomide 7 mg | Experimental | Drug: TeriflunomideTeriflunomide 7 mg: * two tablets once daily for 1 week then, * one tablet once daily for 35 weeks. |
| Teriflunomide 14 mg | Experimental | Drug: TeriflunomideTeriflunomide 14 mg: * two tablets once daily for 1 week then, * one tablet once daily for 35 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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;
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, Teriflunomide 7 mg |
| Placebo (placebo for teriflunomide)film-coated tablet oral administration | Drug | Placebo |
Primary outcome
MRI assessment: number of unique active lesions per scan (T2/proton density and gadolinium-enhanced T1 scan analysis)
Time frame: 36 weeks
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]
Time frame: from first study drug intake up to 6 weeks after last intake or entry in the extension study, whichever came first
AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
6 secondary outcomes
MRI assessment: number of T1-enhancing lesions per scan
Time frame: 36 weeks
MRI assessment: number of T2-lesions per scan
Time frame: 36 weeks
MRI assessment: Number of participants with no new lesions
Time frame: 36 weeks
MRI assessment: Change from baseline in T2 burden of disease
Time frame: 36 weeks
Number of participants with progression on Expanded Disability Status Scale [EDSS]
Time frame: 36 weeks
Number of participants with MS relapse confirmed by Scripps Neurological Rating Scale [NRS] and EDSS scores.
Time frame: 36 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2012.
- Results publication: PubMed 16567708O'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.
- Derived from this study: PubMed 33023488Comi 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.
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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.
Clinical Study Director study director
Clinical Science & Operation - sanofi-aventis
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Teriflunomide in people with Multiple Sclerosis, run by Sanofi at 2 sites in 2 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 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 4 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada, France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
MRI assessment: number of unique active lesions per scan (T2/proton density and gadolinium-enhanced T1 scan analysis) (time frame: 36 weeks). The study lists 2 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 NCT01487096, 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 4 Oct 2012.