A Phase 2 Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of NS-089/NCNP-02 in Boys With Duchenne Muscular Dystrophy (DMD)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 55
- 主要终点
- Urine pharmacokinetic parameters
研究概览
简要总结
This is a Phase 2, open-label, multi-center, 2-part study of NS-089/NCNP-02 administered by weekly IV infusion to ambulant boys aged ≥4 to <15 years with DMD due to mutations amenable to exon 44 skipping. Participants will receive a selected dose of NS-089/NCNP-02 administered once weekly.
The study consists of 2 parts: Part 1 and Part 2. Six participants (Cohort 1) will participate in both Part 1 and Part 2, and 14 participants (Cohort 2) will be added for Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 14 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male ≥ 4 years and <15 years of age
- •Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 44 to restore the dystrophin mRNA reading frame
- •Able to walk independently without assistive devices
- •Ability 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
- •Has a body weight of <20 kg at the time of informed consent (applies to participants screening for Part 1 only)
- •Evidence of symptomatic cardiomyopathy
- •Current or previous treatment with anabolic steroids (e.g., oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug
- •Current or previous treatment with any other investigational drug within 3 months prior to the first dose of study drug or within 5 times the half-life of a medication, whichever is longer
- •Surgery within the 3 months prior to the first dose of study drug or planned during the study duration
- •Previously treated in an interventional study of NS-089/NCNP-02
- •Having received exon skipping oligonucleotide within 1 year prior to the first dose of IP
- •Other exclusion criteria may apply.
研究组 & 干预措施
NS-089/NCNP-02
Experimental: NS-089/NCNP-02
NS-089/NCNP-02 solution for infusion (Cohort 1)
NS-089/NCNP-02 solution for infusion (Cohort 2)
干预措施: NS-089/NCNP-02 (Drug)
结局指标
主要结局
Urine pharmacokinetic parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02
Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot).
时间窗: Baseline, Week25
Adverse Event and Adverse Drug Reaction
时间窗: through study completion, up to follow-up phone call for Part 2
Plasma pharmacokinetic (PK) parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] The volume in the terminal state (Vz) of NS-089/NCNP-02
Plasma pharmacokinetic (PK) parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02
Plasma pharmacokinetic (PK) parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Maximum plasma concentration (Cmax) of NS-089/NCNP-02
Plasma pharmacokinetic (PK) parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Time of the maximum plasma concentration (Tmax) of NS-089/NCNP-02
Plasma pharmacokinetic (PK) parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Terminal half-life (T1/2) of NS-089/NCNP-02
Plasma pharmacokinetic (PK) parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to the last time point (AUC0-t) of NS-089/NCNP-02
Plasma pharmacokinetic (PK) parameters
时间窗: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to infinity (AUC0-∞) of NS-089/NCNP-02
Plasma pharmacokinetic (PK) parameters
时间窗: [Time Frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02
次要结局
- Muscle strength measured by Quantitative Muscle Testing (QMT)(Baseline, Week13, Week25)
- Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.(Baseline, Week25)
- North Star Ambulatory Assessment (NSAA) score(Baseline, Week13, Week25)
- Time to Stand (TTSTAND)(Baseline, Week13, Week25)
- Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.(Baseline, Week25)
- Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin(Baseline, Week25)
- Time to Run/Walk 10 Meters (TTRW)(Baseline, Week13, Week25)
- Total distance of 6 Minute Walk Test (6MWT)(Baseline, Week13, Week25)
- Time to Climb 4 Stairs (TTCLIMB)(Baseline, Week13, Week25)
- Grip and pinch strength(Baseline, Week13, Week25)
- Performance of Upper Limb (PUL) 2.0. score(Baseline, Week13, Week25)