Phase I/II Study of DS-5141b: Open-label Study of DS-5141b in Patients With Duchenne Muscular Dystrophy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy
研究概览
简要总结
This is a phase I/II study to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) profile of DS-5141b in patients with Duchenne muscular dystrophy (DMD) amenable to exon 45 skipping and to determine the dosage for subsequent studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 10 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Confirmation of out-of-frame deletion(s) that could be corrected by dystrophin gene exon 45 skipping.
- •Intact muscles of adequate quality for biopsy to allow evaluation of the efficacy of the study drug.
- •Boys aged from 5 years to <11 years.
- •Patients able to walk at least 325 meters in the 6-minutes walk test.
- •Glucocorticoid-naive patients, or patients who have used glucocorticoids for at least 6 months prior to enrollment in this study with no dose changes for at least 3 months prior to enrollment.
排除标准
- •A genetic mutation that can not be expected the expression of dystrophin protein by dystrophin gene exon 45 skipping.
- •A concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function.
- •Current or history of severe disorder.
- •Left ventricular ejection fraction (LEVF) <55%.
- •Corrected QT interval (QTc) >0.45 sec.
研究组 & 干预措施
DS-5141b
DS-5141b, Subcutaneous injection
Part 1: DS-5141b will be injected subcutaneously once a week for 2 weeks at the following dose levels. Dose escalation will be performed. DS-5141b will be administered at dose levels 1 and 3 in Cohort 1 and at dose levels 2 and 4 in Cohort 2.
- Level 1: 0.1 mg/kg
- Level 2: 0.5 mg/kg
- Level 3: 2.0 mg/kg
- Level 4: 6.0 mg/kg
Part 2: Two doses of DS-5141b will be selected based on the results obtained in Part 1. Each selected dose will be administered subcutaneously once a week for 12 weeks.
Part 2-Extension-2: Two doses, 2.0 mg/kg or 6.0 mg/kg, of DS-5141b will be administered subcutaneously once a week for 48 weeks.
干预措施: DS-5141b (Drug)
结局指标
主要结局
Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) In Participants With Duchenne Muscular Dystrophy
时间窗: 48 Weeks of Part 2-Extension-2
A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during treatment having been absent prior to treatment or reemerges during treatment or worsens in severity during treatment.
Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
时间窗: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
Pharmacokinetic Parameter Half-life (T1/2) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Dystrophy
时间窗: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
Mean Dystrophin Protein Expression in Muscle Tissue
时间窗: Week 48 of Part 2-Extension-2
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
时间窗: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
Pharmacokinetic Parameter Area Under the Curve (AUC) Tau of DS-5141a (Free Form of DS-5141b) in Participants With Duchenne Muscular Dystrophy
时间窗: Week 48 of Part 2-Extension-2
Pharmacokinetic parameters were assessed using non-compartmental methods.
次要结局
- Number of Participants With Exon 45-skipped Dystrophin mRNA Expression in Muscle Tissue Posttreatment(Week 48 of Part 2-Extension-2)