An Open-Label, Systemic Gene Delivery Study to Evaluate the Safety, Tolerability and Expression of Delandistrogene Moxeparvovec Following Plasmapheresis in Subjects With Duchenne Muscular Dystrophy and Pre-existing Antibodies to AAVrh74
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 6
- 主要终点
- Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression Adjusted by Muscle Content Biopsied Muscle as Measured by Western Blot
研究概览
简要总结
This is a gene transfer therapy study evaluating the safety of and delandistrogene moxeparvovec dystrophin protein expression from delandistrogene moxeparvovec following therapeutic plasma exchange (plasmapheresis) in ambulatory male participants with DMD and pre-existing antibodies to AAVrh74 over a period of 59 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 8 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Ambulatory per protocol specified criteria.
- •Has a definitive diagnosis of DMD prior to Screening based on documentation of clinical findings and prior confirmatory genetic testing.
- •Ability to cooperate with motor assessment testing.
- •Has elevated AAVrh74 antibody titers per protocol-specified requirements.
- •A pathogenic frameshift mutation, nonsense mutation or premature stop codon or pathogenic variant in the DMD gene that is expected to lead to absence of dystrophin protein with exception of a mutation in exon 8 and/or
- •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).
排除标准
- •Has reduced left ventricular ejection fraction on the screening ECHO or clinical signs and/or symptoms of cardiomyopathy.
- •Presence of any other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for gene transfer or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability.
- •Exposure to gene therapy, investigational medication, or other protocol-specified treatment within the protocol specified time limits.
- •Abnormality in protocol-specified diagnostic evaluations or laboratory tests. .
- •Note: Other inclusion or exclusion criteria could apply.
结局指标
主要结局
Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression Adjusted by Muscle Content Biopsied Muscle as Measured by Western Blot
时间窗: Baseline, Week 12
Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by Immunofluorescence (IF) Fiber Intensity
时间窗: Baseline, Week 12
Change From Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression in Biopsied Muscle as Measured by IF Percent Dystrophin-positive Fibers (PDPF)
时间窗: Baseline, Week 12
Mean Concentration of Vector Genome Copies Using Polymerase Chain Reaction in Muscle Tissue Biopsy, After Delandistrogene Moxeparvovec Administration
时间窗: Week 12
次要结局
- Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE)(Baseline up to End of Study (Up to Week 59))
- Change from Baseline in rAAVrh74 Antibody Titers(Baseline, Week 1)
- Change from Baseline in rAAVrh74 Antibody Titers(Baseline, Week 1)