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

NCT06114056 | Active Not Recruiting Phase 1

• 1 other identifier: 2023-1285
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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).

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy; Gene Therapy; Adeno-associated virus

Outcome Measures

Primary Outcomes (1)

• adverse events

  Adverse events defined as the number of participants with adverse events according CTCAE v5.0

  5 years

Secondary Outcomes (5)

• North Star Ambulatory Assessment

  5 years

• Six-Minute Walk Test

  5 years

• 10-Meter Walk/Run Test

  5 years

• creatine kinase

  5 years

• the expression of micro-dystrophin gene

  6 months

Study Arms (1)

JWK007 (AAVM101-µDys)

EXPERIMENTAL

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.

Biological: JWK007 Single intravenous infusion administration

Interventions

JWK007 Single intravenous infusion administration BIOLOGICAL

Each patient receives a single intravenous infusion of JWK007 at a dose of 1.0 × 10\^14 vg/kg.

JWK007 (AAVM101-µDys)

Eligibility Criteria

• Age: 5 Years - 10 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 58.
• 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.

You may not qualify if:

• 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).
• 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.
• Has had any type of gene therapy, cell based therapy (eg. stem cell transplantation), or CRISPR/Cas9.
• Family does not want to disclose patient's study participation with primary care physician and other medical providers

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (6)

• Costa Verdera H, Kuranda K, Mingozzi F. AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer. Mol Ther. 2020 Mar 4;28(3):723-746. doi: 10.1016/j.ymthe.2019.12.010. Epub 2020 Jan 10.

  PMID: 31972133 BACKGROUND

• Mendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, Iammarino MA, Alfano LN, Nicholl A, Al-Zaidy S, Lewis S, Church K, Shell R, Cripe LH, Potter RA, Griffin DA, Pozsgai E, Dugar A, Hogan M, Rodino-Klapac LR. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. JAMA Neurol. 2020 Sep 1;77(9):1122-1131. doi: 10.1001/jamaneurol.2020.1484.

  PMID: 32539076 BACKGROUND

• Miesbach W, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Tangelder M, Castaman G, Schwable J, Bonig H, Seifried E, Cattaneo F, Meyer C, Leebeek FWG. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood. 2018 Mar 1;131(9):1022-1031. doi: 10.1182/blood-2017-09-804419. Epub 2017 Dec 15.

  PMID: 29246900 BACKGROUND

• Duan D. Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy. Mol Ther. 2018 Oct 3;26(10):2337-2356. doi: 10.1016/j.ymthe.2018.07.011. Epub 2018 Jul 17.

  PMID: 30093306 BACKGROUND

• Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, Du Z, Jiang W, Zhong C, Wei J, Zhu P, Fu R, Liu X, Chen L, Pei X, Sun J, Cheng T, Yang R, Xiao X, Zhang L. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 2022 Jul;9(7):e504-e513. doi: 10.1016/S2352-3026(22)00113-2. Epub 2022 May 19.

  PMID: 35598604 BACKGROUND

• Roberts TC, Wood MJA, Davies KE. Therapeutic approaches for Duchenne muscular dystrophy. Nat Rev Drug Discov. 2023 Nov;22(11):917-934. doi: 10.1038/s41573-023-00775-6. Epub 2023 Aug 31.

  PMID: 37652974 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Xingchen Xingchen, Ph.D

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Professor

Study Record Dates

• First Submitted: October 29, 2023
• First Posted: November 2, 2023
• Study Start: January 31, 2024
• Primary Completion (Estimated): November 13, 2029
• Study Completion (Estimated): November 13, 2029
• Last Updated: March 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)