A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of Single Intravenous Infusion of JWK007 in Patients With Duchenne Muscular Dystrophy (DMD)
概览
- 阶段
- 1 期
- 干预措施
- JWK007 Single intravenous infusion administration
- 疾病 / 适应症
- Duchenne Muscular Dystrophy
- 发起方
- West China Hospital
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- adverse events
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
This study is a single-center, single-arm, non-randomized, open-label, non-controlled, dose-escalation, prospective clinical trial designed to assess the safety, tolerability, and preliminary efficacy of JWK007 injection in pediatric patients with Duchenne Muscular Dystrophy (DMD).
详细描述
DMD is a rare genetic disorder that primarily affects males. This disease is closely associated with mutations in the DMD gene located on the X chromosome. The DMD gene encodes a protein known as dystrophin, which plays a crucial role in providing essential structural and protective support within the muscles. Gene therapy drugs using Adeno-Associated Virus (AAV) as a vector hold the promise of offering a convenient, effective, and safe treatment option for DMD patients. Therefore, we have independently developed and designed the JWK007 injection. The study was originally designed as a '3+3' dose-escalation trial with two cohorts. However, due to recruitment difficulties at the higher dose level, only the low-dose cohort (N=3) will be enrolled. No further enrollment or dose escalation will be conducted, and all safety, tolerability, and preliminary efficacy endpoints will be assessed in this single low-dose cohort.
研究者
入排标准
入选标准
- •Participants meeting all of the following criteria may be considered for inclusion:
- •Male, aged 5 to 10 years (inclusive).
- •Diagnosis of Duchenne Muscular Dystrophy (DMD) confirmed through medical history and genetic testing, characterized by a frameshift mutation (deletion or duplication) or a premature stop codon mutation in the DMD gene between exons 18 to
- •Below-average performance on motor assessment testing.
- •Ability to cooperate with motor assessment testing.
- •Tolerance for muscle biopsy under anesthesia with no contraindications for biopsy.
- •Participants must have been taking a stable dose of oral corticosteroids for at least 12 weeks prior to screening, and the expected dose should remain constant throughout the study, except for adjustments related to changes in body weight.
排除标准
- •Participants meeting any one of the following criteria are not eligible for inclusion:
- •Active viral infection based on clinical observations.
- •Signs of cardiomyopathy, including echocardiogram with ejection fraction below 40%.
- •Serological evidence of HIV infection, or Hepatitis B or C infection.
- •Diagnosis of (or ongoing treatment for) an autoimmune disease.
- •Abnormal laboratory values considered clinically significant (GGT \> 3XULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.8 mg/dL, Hgb \< 80 or \> 180 g/L; WBC \> 18.5\*10\^9/L).
- •Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer.
- •Subjects with AAVrh74 neutralizing antibody titers \> 1:400 as determined by ELISA immunoassay.
- •Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability.
- •Severe infection (eg. pneumonia, pyelonephritis, or meningitis) within 4 weeks before gene transfer visit (enrollment may be postponed).
研究组 & 干预措施
JWK007 (AAVM101-µDys)
JWK007 injection utilizes AAVM101, an AAVrh74-derived capsid engineered for enhanced muscle targeting, as its viral vector. Because the full-length dystrophin gene exceeds the conventional rAAV packaging capacity (\< 5.0 kb), JWK007 delivers an independently designed micro-dystrophin (μDystrophin) gene. The resulting μDystrophin protein retains essential functional domains, including structures critical for promoting neuronal nitric oxide synthase (nNOS) activity and membrane binding.
干预措施: JWK007 Single intravenous infusion administration
结局指标
主要结局
adverse events
时间窗: 5 years
Adverse events defined as the number of participants with adverse events according CTCAE v5.0
次要结局
- Six-Minute Walk Test(5 years)
- the expression of micro-dystrophin gene(6 months)
- creatine kinase(5 years)
- North Star Ambulatory Assessment(5 years)
- 10-Meter Walk/Run Test(5 years)