A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and Pharmacokinetics of DYNE-251 Administered to Participants with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 16
- 试验地点
- 10
- 主要终点
- Number and proportion of participants with treatment-emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), TEAEs considered related to study drug, and TEAEs leading to discontinuation from study drug and discontinuation from the study.
研究概览
简要总结
"To evaluate the safety and tolerability of multiple IV doses of DYNE-251 administered to participants with DMD
To evaluate dystrophin protein levels in muscle tissue following multiple IV doses of DYNE-251 administered to participants with DMD "
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age 4 to 16 years inclusive, at the time of informed consent/assent. • Male with a confirmed diagnosis of DMD and with a mutation in the dystrophin gene characterized by exon deletion amenable to exon 51 skipping. • Upper extremity muscle group that is amenable to muscle biopsy. • Brooke Upper Extremity Scale score of 1 or
- •Ambulatory or non-ambulatory. A non-ambulatory participant must have been non-ambulatory for <2 years before enrolment. • Receiving a stable dosage of glucocorticoids for at least 12 weeks prior to the start of study drug administration. • Left ventricular ejection fraction of ≥50% by echocardiogram or ≥ 55% by cardiac magnetic resonance imaging (MRI).
排除标准
- •Uncontrolled clinical symptoms and signs of congestive heart failure (CHF). • Any change in prophylaxis/treatment for CHF within 3 months prior to the start of study treatment. • History of major surgical procedure within 12 weeks prior to the start of study drug administration or an expectation of a major surgical procedure during the study. • Requirement of daytime ventilator assistance. • Percent predicted FVC <40 % (applies only for participants who are age ≥7 years). • Receipt of eteplirsen, or alternative exon-skipping/dystrophinmodifying therapy, within 12 weeks of randomization. • Receipt of non-exon skipping investigational drug within 4 months before the start of study drug administration. • Receipt of gene therapy at any time.
结局指标
主要结局
Number and proportion of participants with treatment-emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), TEAEs considered related to study drug, and TEAEs leading to discontinuation from study drug and discontinuation from the study.
Number and proportion of participants with treatment-emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), TEAEs considered related to study drug, and TEAEs leading to discontinuation from study drug and discontinuation from the study.
Change from Baseline in dystrophin protein levels in muscle tissue as determined by Western blot analysis at Week 25
Change from Baseline in dystrophin protein levels in muscle tissue as determined by Western blot analysis at Week 25
次要结局
- Muscle Tissue Endpoints: Cohorts dosed Q4W or Q8W with a second biopsy at Week 25
- Change from Baseline at Week 25: -exon 51 skipping levels in muscle tissue -PDPF in muscle tissue -PMO concentration in muscle tissue
- Change from baseline up to Week 145: -blood CK levels
- Cohorts dosed Q8W with a second biopsy at Week 49 Change from Baseline at Week 49 in: -dystrophin protein levels in muscle tissue -exon 51 skipping levels in muscle tissue -PDPF in muscle tissue -PMO concentration in muscle tissue
- Change from Baseline up to Week 145 in: -blood CK level
- Functional Endpoints: All cohorts
- Change from Baseline up to Week 145 in: -PUL scale V 2.0 score -%pFVC -NSAA total score, TTR, 10MRW, and SV95C in ambulatory participants
- Plasma Endpoints: All cohorts -Cmax -tmax -AUCtlast -AUC∞ -λZ -t½ -CL -Vz and Vss, if appropriate
- Immunogenicity Endpoint: All cohorts -Incidence of ADAs
研究者
Dyne Clinical Trials
Scientific
Dyne Therapeutics Inc.