临床试验/NCT05524883

NCT05524883进行中（未招募）1 期

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

Dyne Therapeutics43 个研究点分布在 9 个国家目标入组 86 人开始时间: 2022年8月12日最近更新: 2026年8月11日

适应症

干预措施

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Dyne Therapeutics
入组人数: 86
试验地点: 43
主要终点: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The primary purpose of this study is to evaluate the safety, tolerability, and dystrophin protein levels in muscle tissue following multiple intravenous (IV) doses of DYNE-251 in participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping.

The study consists of 3 periods: a multiple-ascending dose (MAD) / placebo-controlled period (24 weeks), an open-label period (24 weeks) and a long-term extension (LTE) period (288 weeks).

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Sequential
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 16 Years（Child）
性别: Male
接受健康志愿者: 否

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 enrollment.
•Receiving a stable dosage of glucocorticoids for at least 12 weeks prior to the start of study drug administration, with the expectation of maintaining a stable dose during the Placebo-Controlled and Open-Label Periods of the study (unless dose adjustment is required by weight change).
•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/dystrophin-modifying 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.
•Other inclusion and exclusion criteria may apply.

研究组 & 干预措施

Placebo-Controlled MAD Period - Placebo

Experimental

Placebo will be administered Q4W or Q8W over 24 weeks.

干预措施: Placebo (Drug)

Open-Label and Long-Term Extension Period - DYNE-251

Experimental

DYNE-251 will be administered Q4W or Q8W for up to 288 weeks after participants complete the Placebo-Controlled MAD Period of the study.

干预措施: DYNE-251 (Drug)

Placebo-Controlled MAD Period - DYNE-251

Experimental

DYNE-251 will be administered once every 4 weeks (Q4W) or once every 8 weeks (Q8W) over 24 weeks.

干预措施: DYNE-251 (Drug)

结局指标

主要结局

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

时间窗: Through study completion, up to Week 241

Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25

时间窗: Baseline, Week 25

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

时间窗: Through study completion, up to Week 337

次要结局

Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 25 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25(Baseline, Week 25)
Change From Baseline in Muscle Tissue Percent Dystrophin-Positive Fiber (PDPF) at Week 25 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25(Baseline, Week 25)
Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 241 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25(Baseline, up to Week 241)
Change From Baseline in Dystrophin Protein Level in Muscle Tissue as Determined by Western Blot at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49(Baseline, Week 49)
Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49(Baseline, Week 49)
Change From Baseline in Muscle Tissue PDPF at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49(Baseline, Week 49)
Change From Baseline in Blood CK Levels up to Week 241 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49(Baseline, up to Week 241)
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 241(Baseline, up to Week 241)
Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 241(Baseline, up to Week 241)
Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 241(Baseline, up to Week 241)
Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 241(Baseline, up to Week 241)
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 241(Baseline, up to Week 241)
Change From Baseline in Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 241(Baseline, up to Week 241)
Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax)(Through study completion, up to Week 241)
Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax)(Through study completion, up to Week 241)
Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast)(Through study completion, up to Week 241)
Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC∞)(Through study completion, up to Week 241)
Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (λz)(Through study completion, up to Week 241)
Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½)(Through study completion, up to Week 241)
Total Body Clearance (CL) of DYNE-251(Through study completion, up to Week 241)
Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz)(Through study completion, up to Week 241)
Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss)(Through study completion, up to Week 241)
Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue(Through study completion, up to Week 241)
Percentage of Participants With Antidrug Antibodies (ADAs)(Through study completion, up to Week 241)
Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast)(Through study completion, up to Week 337)
Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 337 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25(Baseline, up to Week 337)
Change From Baseline in Blood CK Levels up to Week 337 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49(Baseline, up to Week 337)
Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax)(Through study completion, up to Week 337)
Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax)(Through study completion, up to Week 337)
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 337(Baseline, up to Week 337)
Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 337(Baseline, up to Week 337)
Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 337(Baseline, up to Week 337)
Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 337(Baseline, up to Week 337)
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 337(Baseline, up to Week 337)
Change From Baseline in Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 337(Baseline, up to Week 337)
Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC∞)(Through study completion, up to Week 337)
Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (λz)(Through study completion, up to Week 337)
Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½)(Through study completion, up to Week 337)
Total Body Clearance (CL) of DYNE-251(Through study completion, up to Week 337)
Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz)(Through study completion, up to Week 337)
Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss)(Through study completion, up to Week 337)
Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue(Through study completion, up to Week 337)
Incidence of Antidrug Antibodies (ADAs)(Through study completion, up to Week 337)

研究者

发起方

Dyne Therapeutics

申办方类型

Industry

责任方

Sponsor

研究点 (43)

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