A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease Types 1 and X
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 63
- 试验地点
- 16
- 主要终点
- Part 2: Percent Change in Muscle Volume to the End of the Double-blind Placebo-controlled Portion of the Study.
研究概览
简要总结
This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with Charcot-Marie-Tooth Disease Type 1 and Type X (CMT1 and CMTX), to be conducted in two parts. Part 1 is non-randomized, open-label, dose-escalation and Part 2 is randomized, double-blind, and placebo-controlled.
详细描述
Part 1 (non-randomized, open-label, dose-escalation)
Part 1 will consist of up to 3 cohorts of 6 patients each and will evaluate multiple ascending dose levels of ACE-083 administered bilaterally once every 3 weeks for up to 5 doses in the tibialis anterior (TA) muscle. Patients in each cohort will be enrolled in a 4-week screening period before beginning treatment.
Part 2 (randomized, double-blind, placebo-controlled) Prior to the initiation of Part 2, a review of safety and efficacy data from Part 1 will be conducted by the Safety Review Team (SRT) to determine the recommended dose level (maximum 250 mg/muscle). A total of up to 40 new patients may be enrolled and randomized (1:1 randomization) to receive either ACE 083 (n=20) or placebo (n=20) bilaterally by injection into both TA muscles once every 3 weeks for up to 17 doses.
Study duration for Parts 1 and 2 for each patient will be approximately 24 weeks, including a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period after the last dose.
Study duration for Part 2 will be 15 months, including 4-week screening, 6 months double blind placebo-controlled, 6 months open-label and 8 week follow-up.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part 1 Cohort 1
ACE-083 150 mg intramuscular (IM) (tibialis anterior muscle), once every 3 weeks for up to 5 doses.
干预措施: ACE-083 (Drug)
Part 1 Cohort 2
ACE-083 200 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.
干预措施: ACE-083 (Drug)
Part 1 Cohort 3
ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.
干预措施: ACE-083 (Drug)
Part 2 (double-blind placebo controlled)
ACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 9 doses
干预措施: ACE-083 (Drug)
Part 2 (double-blind placebo controlled)
ACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 9 doses
干预措施: Placebo (Drug)
Part 2 (open label)
ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 8 doses
干预措施: ACE-083 (Drug)
结局指标
主要结局
Part 2: Percent Change in Muscle Volume to the End of the Double-blind Placebo-controlled Portion of the Study.
时间窗: From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).
The percent change from baseline in volume of injected muscle, by MRI compared to the Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.
Part 1: Frequency of Adverse Events
时间窗: From initiation of treatment (Study Day 1) to end of follow-up period for Part 1 (Study Day 141).
Number of subjects with at least one adverse event related to treatment intervention from Part 1 of this study. Since this outcome measure was only pre-specified for Part 1, only data from the Part 1 participants is reported.
次要结局
- Part 2: Percent Change in Balance and Fall Risk From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Change in Balance and Fall Risk at the End of the Double-blind Placebo-controlled Portion of the Study.(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Percent Change in Clinical Examination Score in Baseline to End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Percent Change in Muscle Strength to the End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Percent Change in Muscle Function - Walk Distance Assessed at the End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period for the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Absolute Change in Amount of Intramuscular Fat Tissue to the End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Percent Change in Muscle Function - Walk/Run Time to the End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Change in Clinical Examination Score From Baseline to End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)
- Part 2: Change in Patient-reported Quality of Life From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study(From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).)