A Phase I/IIa, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous and Intravenous Doses of PRO044 in Patients With Duchenne Muscular Dystrophy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts
研究概览
简要总结
The purpose of this study is to see whether PRO044 is safe and effective to use as medication for DMD patients with a mutation around location 44 in the DNA for the dystrophin protein.
详细描述
To assess the effect of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To assess the safety and tolerability of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To determine the pharmacokinetics of PRO044 at different dose levels after subcutaneous and intravenous administration in subjects with Duchenne muscular dystrophy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Life expectancy of at least 6 months.
- •No previous treatment with investigational medicinal treatment within 6 months prior to the start of the (pre)-screening for the study.
- •No previous treatment with idebenone within 6 months prior to the start of the (pre)-screening for the study.
- •Willing and able to adhere to the study visit schedule and other protocol requirements.
- •Written informed consent signed (by parent(s)/legal guardian and/or the patient, according to the local regulations).
- •Glucocorticosteroids use which is stable for at least 2 months prior first drug administration.
排除标准
- •Aberrant RNA splicing and/or aberrant response to PRO044, detected by in vitro PRO044 assay during pre-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.
- •Use of idebenone.
- •Use of any investigational product within 6 months prior to the start of the (pre)-screening for the study.
- •Subject has donated blood less than 90 days before the start of the (pre)-screening for 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
PRO044, cohort 1
Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29.
干预措施: PRO044 SC (Drug)
PRO044, cohort 2
Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29.
干预措施: PRO044 SC (Drug)
PRO044, cohort 3
Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29.
干预措施: PRO044 SC (Drug)
PRO044, cohort 4
Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29.
干预措施: PRO044 SC (Drug)
PRO044, cohort 5
Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29
干预措施: PRO044 SC (Drug)
PRO044, cohort 6
Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29
干预措施: PRO044 SC (Drug)
PRO044, cohort 7
Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29
干预措施: PRO044 IV (Drug)
PRO044, cohort 8
Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29
干预措施: PRO044 IV (Drug)
PRO044, cohort 9
Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29
干预措施: PRO044 IV (Drug)
结局指标
主要结局
Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts
时间窗: Within 13 weeks after 5 weeks of treatment
Safety and Tolerability of PRO044
时间窗: During the 5 weeks of treatment and during the 13 weeks after treatment
number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044
次要结局
- PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration(Week 1, Week 5)