A Phase III Double-blind, Randomised, Placebo-controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 232
- 试验地点
- 13
- 主要终点
- Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52
研究概览
简要总结
The purpose of this trial is to study the efficacy, safety and tolerability of idebenone in 12 months of treatment in children and adults with Friedreich's Ataxia. This is a randomised placebo-controlled double-blind trial conducted in Europe. Efficacy outcomes include measures of neurological impairment and function, and measures of the heart.
详细描述
Idebenone, a short-chain analogue of Co-enzyme Q10 (CoQ10), has the potential to moderate underlying causes of Friedreich's Ataxia through its antioxidant activity and its role as an electron carrier in the respiratory chain promoting mitochondrial ATP production.
The current 12-month placebo-controlled treatment study in 232 patients aims to confirm the positive effect of idebenone on neurological function, as for instance observed in the recent 48-patient, 6-month NICOSIA study in children, using the International Cooperative Ataxia Rating Scale (ICARS) and the newly developed Friedreich's Ataxia Rating Scale (FARS).
In addition, the study aims to confirm the positive effect on cardiomyopathy associated with FRDA observed in several small studies. Cardiac anatomy and function will be assessed using echocardiography, tissue Doppler imaging and cardiac MRI methods in patients with FRDA cardiomyopathy. In addition exercise capacity, measured as peak workload, will be assessed in patients able to comply with a modified exercise protocol.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of FRDA with confirmed FRDA mutations
- •Patients 8 years of age or older at baseline
- •Patients with body weight ≥ 25kg
- •Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the medication
- •Negative urine pregnancy test at screening and at baseline (women of childbearing potential)
排除标准
- •Treatment with idebenone or Coenzyme Q10 within the past 1 month
- •Pregnancy and/or breast-feeding
- •Clinically significant abnormalities of clinical haematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of SGOT, SGPT, or creatinine
- •Past or present history of abuse of drugs or alcohol
研究组 & 干预措施
Group A: Idebenone
Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day
干预措施: idebenone (Drug)
Group B: Idebenone
Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day
干预措施: idebenone (Drug)
C: Idebenone
Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day
干预措施: idebenone (Drug)
D: Placebo
placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52
时间窗: Baseline and week 52
The International Cooperative Ataxia Rating Scale (ICARS) is a commonly used evaluation and is composed of four clinical sub-scores involving the following: posture and gait, limb coordination, speech and oculomotor function.The ICARS score is the total sum of the sub scores and ranges from 0 to 100, with 100 indicative of the most severely affected outcome.
次要结局
- Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52(Baseline and week 52)
- Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin(week 52)
- Proportion of Patients Improving on Left Ventricular Peak Systolic Strain Rate or Showing a Reduction in Left Ventricular Mass Index (LVMI) With no Worsening in Strain Rate(1 year)
- Change in Peak Systolic Strain Rate From Baseline to Week 52(1 year)
- Change in Peak Workload From Baseline to Week 52(1 year)