Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne Muscular Dystrophy, Gene Therapy, Adeno-associated virus
Brief summary
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).
Detailed description
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.
Interventions
BIOLOGICALJWK007 Single intravenous infusion administration
Each patient receives a single intravenous infusion of JWK007 at a dose of 1.0 × 10\^14 vg/kg.
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
5 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
Participants meeting all of the following criteria may be considered for inclusion: 1. Male, aged 5 to 10 years (inclusive). 2. 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 58. 3. Below-average performance on motor assessment testing. 4. Ability to cooperate with motor assessment testing. 5. Tolerance for muscle biopsy under anesthesia with no contraindications for biopsy. 6. 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.
Exclusion criteria
Participants meeting any one of the following criteria are not eligible for inclusion: 1. Active viral infection based on clinical observations. 2. Signs of cardiomyopathy, including echocardiogram with ejection fraction below 40%. 3. Serological evidence of HIV infection, or Hepatitis B or C infection. 4. Diagnosis of (or ongoing treatment for) an autoimmune disease. 5. 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). 6. Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer. 7. Subjects with AAVM101 neutralizing antibody titers \> 1:400 as determined by ELISA immunoassay. 8. 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. 9. Severe infection (eg. pneumonia, pyelonephritis, or meningitis) within 4 weeks before gene transfer visit (enrollment may be postponed). 10. Has received any investigational medication (other than corticosteroids) or exon skipping medications (including ExonDys 51), experimental or otherwise, in the last 6 months prior to screening for this study. 11. Has had any type of gene therapy, cell based therapy (eg. stem cell transplantation), or CRISPR/Cas9. 12. Family does not want to disclose patient's study participation with primary care physician and other medical providers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| adverse events | 5 years | Adverse events defined as the number of participants with adverse events according CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| North Star Ambulatory Assessment | 5 years | North Star Ambulatory Assessment (NSAA) is a clinical tool used to assess the motor function and ambulatory capabilities of children and adolescents with neuromuscular disorders like Duchenne muscular dystrophy. |
| Six-Minute Walk Test | 5 years | the distance the patient walked in six minutes |
| 10-Meter Walk/Run Test | 5 years | The time it takes to walk 100 meters |
| creatine kinase | 5 years | Changes in circulating levels of CK |
| the expression of micro-dystrophin gene | 6 months | Baseline muscle biopsies for dystrophin expression will be performed between -30 and -7 days prior to treatment in all subjects. All subjects will undergo a post-treatment biopsy on day 180. Micro-dystrophin gene expression was quantified (immunofluorescence and Western blot analysis) and compared before and after muscle biopsy. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORXingchen Xingchen, Ph.D
West China Hospital
Outcome results
None listed