A Phase 1/2a, Multi-center, Open-label Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of PBGENE-DMD in Participants With Duchenne Muscular Dystrophy (FUNCTION-DMD)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Incidence, severity, and causality of treatment-emergent adverse events and serious adverse events
研究概览
简要总结
The purpose of this Phase 1/2a trial is to evaluate the safety, tolerability, and preliminary efficacy of PBGENE-DMD in patients with DMD harboring mutations amenable to excision of exons 45-55. Given the limitations of existing therapeutic strategies, PBGENE-DMD represents a novel, innovative approach with the potential for a one-time, durable correction of the underlying genetic defect in the largest molecular subset of patients with DMD.
详细描述
This is a Phase 1/2a, open-label, multicenter trial designed to evaluate the safety, tolerability, and primary efficacy of a single IV dose of PBGENE-DMD in male participants with DMD presenting with mutations that may be amenable to treatment with PBGENE-DMD. A structured, multimodal, short-term immunomodulatory regimen will be administered around the time of dosing to mitigate the risk of potential immune-mediated responses.
The trial consists of two parts: Part 1 is to confirm a safe and well-tolerated single dose of PBGENE-DMD that may be further evaluated in Part 2 (expansion).
A total of up to 18 participants may be enrolled in this trial. Total duration of trial participation for each participant: approximately 130 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
盲法说明
Open label
入排标准
- 年龄范围
- 2 Years 至 7 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males, 2 to 7 years of age, inclusive, at the time of informed consent/assent
- •Molecular confirmed DMD diagnosis (DMD mutation fully contained between exons 45 to 55 [inclusive])
- •Clinical phenotype consistent with DMD in the opinion of the Investigator
- •Ability to complete age-appropriate motor testing assessments requirements.
- •Participants aged 2 to < 4 years at the time of screening must:
- •Be able to walk at least 10 meters independently (without assistive devices).
- •Be able to rise from the floor without physical assistance (use of a Gowers' maneuver is acceptable).
- •Participants aged 4 to 7 years at the time of screening must:
- •Be able to walk at least 100 meters independently (without assistive devices).
- •Have an NSAA total score between 16 and 29, inclusive.
- •Participant has received age-appropriate routine childhood immunizations per the local country's national immunization schedule.
- •The participant's parent(s)/LAR(s) are willing and able to provide written informed consent prior to the initiation of any trial-specific procedures; where applicable, the participant must provide written or verbal assent in accordance with local regulations.
- •The participant and their parent(s)/LAR(s) are willing to participate in a LTFU study after the completion of this trial.
排除标准
- •Prior treatment with any gene therapy, gene editing therapy, or cell-based therapy at any time.
- •Receipt of any investigational medication or experimental therapy within 6 months prior to Day
- •Prior or ongoing use of any product designed to increase dystrophin expression, investigational, or otherwise, including exon-skipping therapies, within 6 months of the scheduled Day 1 dose or inability or unwillingness to refrain from initiating or resuming these therapies for at least 5 years following gene therapy administration.
- •Prior ongoing use of any product designed to increase dystrophin expression, investigational, or otherwise, including exon-skipping therapies, within 6 months of the scheduled Day 1 dose.
- •Concurrent enrollment in another clinical trial, unless it is observational (non-interventional).
- •A positive test for antibodies to AAV9
- •A participant has any condition that would contraindicate treatment with immunosuppression.
- •Participants with pathogenic mutations in exons 1-44 and/or exons 56-
- •Evidence of cardiomyopathy or clinically significant left ventricular dysfunction, defined as LVEF <50% on screening echocardiogram.
研究组 & 干预措施
Experimental- Part 1 (Initial Safety) & Part 2 (Expansion) cohort
The trial is planned to enroll participants into 2 parts as follows:
- Part 1 (Initial Safety) A total of up to 6 participants may be enrolled.
- Part 2 (Expansion) Up to 12 participants
干预措施: PBGENE-DMD (IV) (Biological)
结局指标
主要结局
Incidence, severity, and causality of treatment-emergent adverse events and serious adverse events
时间窗: From Dosing through Week 104
Adverse events and serious adverse events that occur or worsen after initiation of the investigational treatment
次要结局
- Dystrophin expression in skeletal muscle(Week 12, Week 52)