An International, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Two Year Treatment With Teriflunomide 7 mg Once Daily and 14 mg Once Daily Versus Placebo in Patients With a First Clinical Episode Suggestive of Multiple Sclerosis Plus a Long Term Extension Period
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 618
- 试验地点
- 131
- 主要终点
- Core Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)
研究概览
简要总结
The primary objective was to demonstrate the effect of teriflunomide (HMR1726) (14 milligram per day [mg/day] and 7 mg/day), in comparison to placebo, for reducing conversion of participants presenting with their first clinical episode consistent with multiple sclerosis (MS) to clinically definite multiple sclerosis (CDMS).
The secondary objectives were:
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To demonstrate the effect of teriflunomide, in comparison to placebo, on:
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Reducing conversion to definite multiple sclerosis (DMS)
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Reducing annualized relapse rate (ARR)
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Reducing disease activity/progression as measured by Magnetic Resonance Imaging (MRI)
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Reducing accumulation of disability for at least 12 weeks as measured by the Expanded Disability Status Scale (EDSS)
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Proportion of disability-free participants as assessed by the EDSS
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Reducing participant-reported fatigue
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To evaluate the safety and tolerability of teriflunomide
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To evaluate the pharmacokinetics (PK) of teriflunomide
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Optional pharmacogenomic testing aimed at assessing the association between the main enzyme systems of teriflunomide metabolism and hepatic safety, and other potential associations between gene variations and clinical outcomes
详细描述
The study consisted of 4 periods:
- Screening period: up to 4 weeks,
- Placebo-controlled treatment period: up to 108 weeks (at least 24 weeks for participants who experienced conversion to CDMS),
- Extension treatment period (without placebo-control): the extension period continued until teriflunomide was commercially available in participant's country of residence.
- Post-treatment washout period: 4 weeks after last treatment intake.
The maximal duration of the study period per participant was expected to be 116 weeks if he/she did not continue in the extension treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •First acute or subacute, well-defined neurological event consistent with demyelination (that is, optic neuritis confirmed by an ophthalmologist, spinal cord syndrome, brainstem/cerebellar syndromes)
- •Onset of MS symptoms occurring within 90 days of randomization
- •A screening MRI scan with 2 or more T2 lesions at least 3 millimeter (mm) in diameter that are characteristic of MS
排除标准
- •Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease
- •Significantly impaired bone marrow function
- •Pregnancy or nursing
- •Alcohol or drug abuse
- •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 participant's potential participation in a clinical trial.
研究组 & 干预措施
Placebo/Teriflunomide 7 mg or Teriflunomide 14 mg
Core treatment period: Placebo matched to teriflunomide tablet once daily orally.
Extension treatment period: Re-randomized in 1:1 ratio to either teriflunomide 7 mg or 14 mg once daily orally.
干预措施: Teriflunomide (Drug)
Placebo/Teriflunomide 7 mg or Teriflunomide 14 mg
Core treatment period: Placebo matched to teriflunomide tablet once daily orally.
Extension treatment period: Re-randomized in 1:1 ratio to either teriflunomide 7 mg or 14 mg once daily orally.
干预措施: Placebo (Drug)
Teriflunomide 7 mg/7 mg
Core treatment period: Teriflunomide 7 mg tablet once daily orally.
Extension treatment period: Teriflunomide 7 mg tablet once daily orally.
干预措施: Teriflunomide (Drug)
Teriflunomide 14 mg/14 mg
Core treatment period: Teriflunomide 14 mg tablet once daily orally.
Extension treatment period: Teriflunomide 14 mg tablet once daily orally.
干预措施: Teriflunomide (Drug)
结局指标
主要结局
Core Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)
时间窗: Up to a maximum of 108 weeks depending on time of enrollment
Conversion to CDMS was defined by the occurrence of a relapse, which was defined as a new neurological abnormality separated by at least 30 days from onset of a preceding clinical event, presented for at least 24 hours and occurred in the absence of fever or known infection. Percent probability of conversion at 24, 48, and 108 weeks was estimated using Kaplan-Meier method.
次要结局
- Core Treatment Period: Time to Conversion to Definite Multiple Sclerosis (DMS)(Up to a maximum of 108 weeks depending on time of enrollment)
- Core Treatment Period: Brain MRI Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan (Poisson Regression Estimates)(Up to a maximum of 108 weeks depending on time of enrollment)
- Core Treatment Period: Brain MRI Assessment: Volume of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan(Up to a maximum of 108 weeks depending on time of enrollment)
- Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of Hypointense Post-Gadolinium T1 Lesion Component(Baseline, Week 108)
- Core Treatment Period: Brain Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Lesion Volume at Week 108(Baseline, Week 108)
- Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of T2 Lesion Component(Baseline, Week 108)
- Core Treatment Period: Time to 12-Week Sustained Disability Progression(Up to a maximum of 108 weeks depending on time of enrollment)
- Core Treatment Period: Change From Baseline in EDSS at Week 108(Baseline, Week 108)
- Core Treatment Period: Overview of Adverse Events (AEs)(From first study drug intake up to 112 days after last intake in the placebo-controlled period or up to first intake in the extension treatment period, whichever occurred first)
- Extension Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)(From randomization in the core period up to 390 Weeks (Extension treatment period [maximum exposure: 283 Weeks]))
- Core Treatment Period: Annualized Relapse Rate (ARR)(Up to a maximum of 108 weeks depending on time of enrollment)
- Core Treatment Period: Brain MRI Assessment: Percent Change From Baseline in Atrophy(Baseline, Week 108)
- Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 108(Baseline, Week 108)
- Extension Treatment Period: Overview of Adverse Events (AEs)(From re-randomization up to 283 Weeks)