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 Glatiramer Acetate in Subjects With Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 123
- 试验地点
- 1
- 主要终点
- Overview of Adverse Events (AE]
研究概览
简要总结
The primary objective was to estimate the tolerability and safety of 2 doses of Teriflunomide administered once daily for 24 weeks, compared to placebo, in patients with multiple sclerosis [MS] with relapses who were on a stable dose of Glatiramer Acetate [GA].
The secondary objectives were:
- to estimate the effect of the 2 doses of Teriflunomide, compared to placebo, in combination with a stable dose of GA 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 GA.
详细描述
The duration of the study period for a 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.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •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 Glatiramer Acetate [GA] 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.
排除标准
- •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.
研究组 & 干预措施
Placebo + GA
Placebo (for teriflunomide) once daily concomitantly with glatiramer acetate (GA) for 24 weeks
干预措施: Placebo (for teriflunomide) (Drug)
Placebo + GA
Placebo (for teriflunomide) once daily concomitantly with glatiramer acetate (GA) for 24 weeks
干预措施: Glatiramer Acetate (GA) (Drug)
Teriflunomide 7 mg + GA
Teriflunomide 7 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks
干预措施: Teriflunomide (Drug)
Teriflunomide 7 mg + GA
Teriflunomide 7 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks
干预措施: Glatiramer Acetate (GA) (Drug)
Teriflunomide 14 mg + GA
Teriflunomide 14 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks
干预措施: Teriflunomide (Drug)
Teriflunomide 14 mg + GA
Teriflunomide 14 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks
干预措施: Glatiramer Acetate (GA) (Drug)
结局指标
主要结局
Overview of Adverse Events (AE]
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
- Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)(baseline (before randomization) and 24 weeks)
- Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)(24 weeks)
- Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan(24 weeks)
- Annualized Relapse Rate [ARR]: Poisson Regression Estimates(24 weeks)
- Pharmacokinetic [PK]: Teriflunomide Plasma Concentration(24 weeks)