A Phase 1/2, First in Human, Multiple-dose, 2-part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NS-050/NCNP-03 in Boys With Duchenne Muscular Dystrophy (DMD)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 27
- 主要终点
- Part 1: Overall Summary of Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a Phase 1/2 study of Multiple-Ascending Dose (MAD) levels for 12 weeks of treatment followed by 24 weeks of open-label treatment with a selected dose of NS-050/NCNP-03 administered once weekly to ambulant boys with DMD, who have a DMD exon deletion amenable to exon 50 skipping.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Years 至 15 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male ≥ 4 years and <16 years of age;
- •Confirmed DMD exon deletion in the dystrophin gene that is amenable to skipping of exon 50 to restore the dystrophin mRNA reading frame;
- •Able to walk independently without assistive devices;
- •Able to complete the TTSTAND without assistance in <20 seconds;
- •Stable dose of glucocorticoid for at least 3 months and the dose is expected to remain on a stable dose for the duration of the study.
- •Other inclusion criteria may apply.
排除标准
- •Evidence of symptomatic cardiomyopathy;
- •Current or previous treatment with anabolic steroids (e.g., oxendolone, oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug;
- •Currently taking another investigational drug or has taken another investigational drug within 3 months prior to the first dose of study drug;
- •Surgery within the 3 months prior to the first dose of study drug or planned during the study duration;
- •Having taken any gene therapy.
- •Other exclusion criteria may apply.
研究组 & 干预措施
Part 1: Placebo
Participants will be randomized and receive NS-050/NCNP-03 placebo-matching IV infusions once weekly for 2 weeks at each of MAD levels.
干预措施: Placebo (Drug)
Part 2: NS-050/NCNP-03
Participants will receive NS-050/NCNP-03 IV infusions once weekly for 24 weeks at the dosage selected by the Data and Safety Monitoring Board (DSMB) at the conclusion of Part 1.
干预措施: NS-050/NCNP-03 (Drug)
Part 1: NS-050/NCNP-03
Participants will be randomized and receive NS-050/NCNP-03 intravenous (IV) infusions once weekly for 2 weeks at each of MAD levels (1.95, 5, 10, 20, 40, and 80 mg/kg).
干预措施: NS-050/NCNP-03 (Drug)
结局指标
主要结局
Part 1: Overall Summary of Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline up to Week 24
TEAEs will be summarized both at the patient level for number of TEAEs, highest severity, relationship, action, and outcome, and at the TEAE level (summarizing events) by system organ class (SOC) and preferred term (PT) as well as severity, relationship, action, and outcome. The most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) will be used for coding TEAEs.
Part 1: Amount of Drug Excreted in Urine of NS-050/NCNP-03
时间窗: Day 1 (1st dose) for each dose level
Urine samples will be collected at the designated time frame. PK parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods.
Part 2: Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot)
时间窗: Baseline, Week25
Part 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of NS-050/NCNP-03
时间窗: Day 1 (1st dose) for each dose level
Blood samples will be collected at the designated time frame. Pharmacokinetic (PK) parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods.
次要结局
- Part 2: Change from baseline in skeletal muscle dystrophin protein by mass spectrometry(Baseline, Week25)
- Part 2: North Star Ambulatory Assessment (NSAA) score(Baseline, Week13, Week25)
- Part 2: Time to Stand (TTSTAND)(Baseline, Week13, Week25)
- Part 2: Time to Run/Walk 10 Meters (TTRW)(Baseline, Week13, Week25)
- Part 2: Total distance of 6 Minute Walk Test (6MWT)(Baseline, Week13, Week25)
- Part 2: Time to Climb 4 Stairs (TTCLIMB)(Baseline, Week13, Week25)
- Part 2: Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining(Baseline, Week25)
- Part 2: Muscle strength measured by Quantitative Muscle Testing (QMT)(Baseline, Week13, Week25)
- Part 2: Grip/Pinch Strength(Baseline, Week13, Week25)
- Part 2: Performance of Upper Limb (PUL) 2.0. score(Baseline, Week13, Week25)
- Part 2: Change from baseline in percentage of exon 50-skipped mRNA of skeletal muscle dystrophin(Baseline, Week25)