A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of SRP- 9001 in Non-Ambulatory and Ambulatory Subjects With Duchenne Muscular Dystrophy (ENVISION)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 148
- 试验地点
- 88
- 主要终点
- Part 1: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) (Version 2.0) at Week 72
研究概览
简要总结
The study will evaluate the safety and efficacy of delandistrogene moxeparvovec gene transfer therapy in non-ambulatory and ambulatory males with DMD. This is a randomized, double-blind, placebo-controlled 2-part study. Participants will be in the study for approximately 128 weeks. All participants will have the opportunity to receive intravenous (IV) delandistrogene moxeparvovec in either Part 1 or Part 2.
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
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
- •Cohort 1 only: Non-ambulatory per protocol-specified criteria.
- •Cohort 2 only: Ambulatory per protocol-specified criteria and ≥8 to <18 years of age at the time of Screening.
- •Ability to cooperate with motor assessment testing.
- •Stable daily dose of oral corticosteroids for at least 12 weeks prior to Screening, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
- •Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) antibody titers are not elevated as per protocol-specified requirements.
- •A pathogenic frameshift mutation or premature stop codon in the DMD gene, except for any deletion mutations in exon 8 and/or 9.
排除标准
- •Exposure to gene therapy, investigational medication, or any treatment designed to increase dystrophin expression within protocol specified time limits.
- •Abnormality in protocol-specified diagnostic evaluations or laboratory tests.
- •Presence of any other clinically significant illness, medical condition, or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risk for gene transfer.
- •Other inclusion or exclusion criteria could apply.
研究组 & 干预措施
Delandistrogene Moxeparvovec followed by Placebo
Participants will receive single IV infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at approximately 72 weeks.
干预措施: placebo (Genetic)
Placebo followed by Delandistrogene Moxeparvovec
Participants will receive matching placebo IV infusion on Day 1. Then, participants will have the opportunity to receive a single IV infusion of delandistrogene moxeparvovec at approximately 72 weeks.
干预措施: placebo (Genetic)
Delandistrogene Moxeparvovec followed by Placebo
Participants will receive single IV infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at approximately 72 weeks.
干预措施: delandistrogene moxeparvovec (Genetic)
Placebo followed by Delandistrogene Moxeparvovec
Participants will receive matching placebo IV infusion on Day 1. Then, participants will have the opportunity to receive a single IV infusion of delandistrogene moxeparvovec at approximately 72 weeks.
干预措施: delandistrogene moxeparvovec (Genetic)
结局指标
主要结局
Part 1: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) (Version 2.0) at Week 72
时间窗: Baseline, Week 72
次要结局
- Part 1: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 72(Baseline, Week 72)
- Part 1: Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 72(Baseline, Week 72)
- Part 1 (For Cohort 2 Only): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 72(Baseline, Week 72)
- Part 1: Change From Baseline in Global Circumferential Strain as Measured by Cardiac MRI at Week 72(Baseline, Week 72)
- Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot(Week 12)
- Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score in Upper Extremity Function to Week 72(Baseline, Week 72)
- Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE)(Baseline up to Week 124)
- Part 1: Change From Baseline in the Middle Domain Score of PUL (Version 2.0) at Week 72(Baseline, Week 72)