A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for Intravenous Dosing as an Alternative Route of Administration
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 主要终点
- Acute phase: Safety data
研究概览
简要总结
The purpose of the extension phase of this study is to determine whether Drisapersen is effective in the treatment of boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.
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 16 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Boys aged between 5 and 16 years inclusive.
- •Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO
- •Not ventilator dependent.
- •Life expectancy of at least six months.
- •No previous treatment with investigational medicinal treatment within six months prior to the study.
- •Willing and able to adhere to the study visit schedule and other protocol requirements.
排除标准
- •Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during screening.
- •Known presence of dystrophin in 5% of fibers in a pre-study diagnostic muscle biopsy.
- •Severe muscle abnormalities defined as increased signal intensity in >50% of the tibialis anterior muscle at MRI.
- •FEV1 and/or FVC <60% of predicted.
- •Current or history of liver or renal disease.
- •Acute illness within 4 weeks prior to treatment (Day 1) which may interfere with the measurements.
- •Severe mental retardation which in the opinion of the investigator prohibits participation in this study.
- •Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study.
- •Need for mechanical ventilation.
- •Creatinine concentration above 1.5 times the upper limit of normal (age corrected).
- •Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment.
- •Use of anticoagulants, antithrombotics or antiplatelet agents.
- •Subject has donated blood less than 90 days before the start of the study.
- •Current or history of drug and/or alcohol abuse.
- •Participation in another trial with an investigational product.
研究组 & 干预措施
Drisapersen
Extension phase of treatment. Intravenous dosing of drisapersen will be investigated as an alternative route of administration
干预措施: Drisapersen (Drug)
结局指标
主要结局
Acute phase: Safety data
时间窗: 18 weeks
Summarized per dose group
Acute phase and Continued Treatment Phase : Pharmacokinetics measured by T1/2, Cmax, Ctrough, 7d, tmax, and volume of distribution and clearance
时间窗: 18 weeks
Plasma concentration versus time profiles of PRO051 (GSK2402968)
Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs)
时间窗: 72 weeks
Change from baseline and summarized values
Continued Treatment Phase :Safety as assessed by laboratory parameters
时间窗: 72 weeks
Change from baseline and summarized values
次要结局
- Continued Treatment Phase: Muscle function(300 weeks)
- Continued Treatment Phase: Muscle strength(300 weeks)
- Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA)(18 weeks)
- Acute phase: Muscle function(18 weeks)
- Continued Treatment Phase Dystrophin expression in muscle biopsy(72 weeks)
- Continued Treatment Phase: Exon skip efficiency(72 weeks)
- Acute phase: Presence of dystrophin expression(18 weeks)
- Acute phase: Muscle strength(18 weeks)