A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of Single Intravenous Infusion of JWK007 in Patients With Duchenne Muscular Dystrophy (DMD)

Sichuan University

Status and phase: Enrolling; Phase 1

Conditions: Duchenne Muscular Dystrophy

Treatments: Biological: JWK007 Single intravenous infusion administration

Study type: Interventional

Funder types: Other

Identifiers

NCT06114056

2023-1285

Details and patient eligibility

About

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).

Full 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 will include two dosing groups and employ a '3+3' dose escalation design, incrementally increasing dosages in a sequential, ascending manner.

Enrollment: 6 estimated patients

Sex: Male

Ages: 5 to 10 years old

Volunteers: No Healthy Volunteers

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 AAVrh74 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

JWK007 injection

Experimental group

Description:

AAVrh74 was used as the vector for JWK007 injection. Because the Dystrophin gene is too large to be used for conventional rAAV loading (AAV packaging capacity \< 5.0kb), we independently designed a new micro-dystrophin (μDystrophin) for each functional domain of the gene. The protein includes structures essential for promoting neuronal nitric oxide synthase (nNOS) activity and membrane-binding domains.

Treatment:

Biological: JWK007 Single intravenous infusion administration