A Single-Arm, Open-Label, Single-Dose Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of BBM-D101 Injection in Patients with Duchenne Muscular Dystrophy
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicity (DLT) events
研究概览
简要总结
The purpose of the study is to assess the safety, tolerability, and efficacy of BBM-D101 to treat patients with Duchenne Muscular Dystrophy.
详细描述
This is a single-arm, open-label study to evaluate the safety, tolerability, efficacy, pharmacokinetic, pharmacodynamic, and immune response of BBM-D101 within 52 weeks after a single intravenous infusion in DMD boys, as well as the long-term safety and efficacy of BBM-D101 for up to 5 years post infusion.
BBM-D101 is gene addition therapy based on engineered AAV delivery therapeutic protein gene cassette into muscle for treating DMD. Therapeutic protein could mediate the dystrophin-associated protein complex to prevent muscular dystrophy and to rescue the function of muscle.
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
- •The legal guardian of the subject fully understands the purpose, nature, methods, and possible risks of the study, and signs a written informed consent form;
- •The study includes ambulatory male subjects who are at least 4 years old and less than 8 years old (4 years old ≤ age < 8 years old) ;
- •Genetically confirmed diagnosis of DMD;
- •Have at least 1 of the following typical clinical signs or laboratory abnormalities of DMD: proximal muscle weakness, waddling gait, pseudo gastrocnemius hypertrophy, Gower's sign, pterygoid scapula;
- •Ability to cooperate with motor assessment testing, magnetic resonance imaging (MRI) and muscle biopsy according to the requirements of the study.
排除标准
- •Hepatitis B surface antigen (HBsAg) positive, hepatitis B virus deoxyribonucleic acid (HBV-DNA) ≥1000U/mL, hepatitis C virus ribonucleic acid (HCV-RNA) positive or human immunodeficiency virus (HIV) positive;
- •Receiving antiviral therapy for hepatitis B, hepatitis C, HIV, etc.;
- •Left ventricular ejection fraction (LVEF) <50% or ≥ class III cardiac function defined by New York Heart Association (NYHA);
- •With severe or persistent arrhythmias and congenital heart disease.
- •The subject's preventive treatment/cardiomyopathy treatment changes within 1 month before the start of the study treatment;
- •With underlying liver disease, such as previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, or hepatic fibrosis ≥ stage 3; or nodules, cysts found by B-ultrasound in the past, or elevated alpha-fetoprotein in laboratory tests during the screening period, etc., and these abnormalities are judged by the investigator to be clinically significant;
结局指标
主要结局
Incidence of dose limiting toxicity (DLT) events
时间窗: 12 weeks
To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-D101 injection infusion.
The incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 52 weeks
To assess the safety of BBM-D101 Injection by AEs and SAEs.
次要结局
- Changes from baseline in the time to ascend 10-meter walk/run test (10MWR) without assistance(52 weeks)
- Changes from baseline in the North Star Ambulatory Assessment (NSAA)(52 weeks)
- Changes from baseline in the time to ascend time to rise (TTR) without assistance without assistance(52 weeks)
- Changes from baseline in the time to ascend 4 steps (4-stair climb, 4SC) without assistance(52 weeks)
- Changes from baseline in the time to ascend 100-meter walk/run test (100MWR) without assistance(52 weeks)
- Changes from baseline in BBM-D101 genome copies in muscle biopsy samples(52 weeks)
- Changes from baseline in BBM-D101 therapeutic protein level in muscle biopsy samples(52 weeks)
研究者
Jiwen Wang
study chair
Shanghai Jiao Tong University School of Medicine