A Phase 1/2, Open-Label, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Intravenous Doses of BMN 351 in Participants With Duchenne Muscular Dystrophy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 8
- 主要终点
- To evaluate and safety and tolerability of single and multiple doses of BMN 351 (incidence, severity, and dose-relationship of adverse effects and changes in laboratory parameters).
研究概览
简要总结
The purpose of this study is to test the safety and tolerability of BMN 351 in participants with Duchenne Muscular Dystrophy (DMD) with a genetic mutation amenable to exon 51 skipping.
详细描述
This is Phase 1/2, open-label, multi-center study consisting of 2 parts to evaluate the safety and tolerability of BMN 351 at escalating doses in participants with Duchenne Muscular Dystrophy (DMD) with genetic mutations amenable to exon 51 skipping.
Participants will be assigned to one of three groups called cohorts (Cohort 1, 2 or 3). Cohort 1 participants are further divided into Cohort 1A and Cohort 1B. In Cohort 1A, 3 participants will receive increasing doses once every 2 weeks with a visit to assess safety measures collected the week after dosing prior to escalating doses of BMN 351. In part 2, the participants in cohort 1A will transition to once weekly dosing. The participants in Cohort 1B, 2, and 3 will initiate low, medium, and high doses of BMN 351 and continue once weekly dosing at that same dose. The study will enroll approximately 18 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 10 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Age 4 to 10
- •Diagnosis of Duchenne muscular dystrophy with a specific genetic change amenable to exon 51 skipping
- •Able to walk
- •Not requiring assistance from a ventilator to breathe
- •Currently on consistent doses of steroid treatment for the last 12 weeks
排除标准
- •The participant will have some initial clinical labs and studies to assess baseline level of heart and lung function.
- •Treatment with an exon skipping therapy within 12 weeks prior to the first visit.
- •Any history of treatment with gene therapy
研究组 & 干预措施
Cohort 1B
BMN 351 low dose will be administered once weekly for up to 97 weeks
干预措施: BMN 351 (Drug)
Cohort 2
BMN 351 medium dose will be administered once weekly for up to 73 weeks
干预措施: BMN 351 (Drug)
Cohort 3
BMN 351 high dose will be administered once weekly for up to 48 weeks
干预措施: BMN 351 (Drug)
Cohort 1A
Cohort 1A will consist of both a single ascending dose (SAD) part and a multiple ascending dose (MAD). BMN 351 will be administered once every 2 weeks during the SAD portion of the study for up to 8 weeks and once weekly during the MAD portion for up to 89 weeks.
干预措施: BMN 351 (Drug)
结局指标
主要结局
To evaluate and safety and tolerability of single and multiple doses of BMN 351 (incidence, severity, and dose-relationship of adverse effects and changes in laboratory parameters).
时间窗: Up to 97 weeks.
The safety and tolerability of BMN 351 will be assessed based on the incidence of adverse and serious adverse events.
次要结局
- Pharmacokinetics (PK) concentration of BMN 351 in plasma, urine and muscle approximately every 8 weeks for up to 97 weeks.(Serial measurements pre and post infusion.)