An Open-label, Multidose Dose-escalation Study to Understand the Safety of CRISPR Gene-editing Therapy and Its Long-Lasting Effects in DMD Patients (MUSCLE)

NCT06594094 | Completed Early Phase 1

• 1 other identifier: HG30201
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Duchenne muscular dystrophin (DMD) is an X-linked, fatal muscle-wasting disease caused by mutations in the DMD gene encoding the dystrophin proteins, with symptom onset before age of 6 years in boys. These mutations abolish dystrophin production in the muscle, leading to dystrophin deficiency at the myofiber membrane, continued fiber degeneration, the need for assisted ventilation, respiratory inflammation, loss of walking ability in their teens, followed by respiratory and cardiac decline, and eventually premature death before the age of 30. Currently, there are only glucocorticoids for the standard supportive therapy of DMD, which can improve disease symptoms but do not change the outcome of the disease, Three antisense oligonucleotide (ASOs) medicines have been approved to treat DMD with exon 45-55 hotspot region mutations. However, they can only restore trace amounts of dystrophin protein, which is insufficient to bring real clinical benefits. Gene replacement therapy has been approved using adeno-associated virus (AAV) vectors to deliver the "mini-dystrophin" gene. Yet, mini-dystrophin gene-expression versions of truncated dystrophin functionality are sacrificed and limited. HG302 uses a single AAV vector to deliver the CRISPR/hfCas12Max DNA editing system in the human DMD exon 51 splice donor site. Preclinical studies have shown that a single intravenous injection of HG302 significantly restores dystrophin protein expression in muscle fibers and rescues their muscle function in humanized DMD mice to wild-type levels, with long-lasting and durable efficacy.

Conditions

Duchenne Muscular Dystrophin (DMD)

Keywords

DMD; dystrophin; Gene-editing; HG302; CRISPR

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of systemic adverse events

  Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)

  26 weeks

Secondary Outcomes (3)

• Change from baseline in percentage of dystrophin positive fiber

  26 weeks

• Change from baseline in dystrophin fiber intensity

  26 weeks

• Change from baseline in North Star Ambulatory Assessment scale

  26 weeks

Study Arms (1)

HG302

EXPERIMENTAL

The study will enroll up to 2 dose cohorts

Genetic: HG302

Interventions

HG302 GENETIC

Once intravenous injection; The duration of the study is about 32 weeks for each subject, including a 6 weeks screening period, enrollment visit, treatment visit, and 26 weeks follow-up period.

HG302

Eligibility Criteria

• Age: 4 Years - 8 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males ≥ 4 and ≤8 years at the time of signing informed consent, with clinical diagnosis of DMD;
• DMD gene mutation types are deletions in exons 52, 52-61, or 52-63;
• Able to walk at least 10 meters independently;
• Willing to cooperate with muscle biopsy test;
• Acceptable hematology, clinical chemistry, and urine laboratory parameters.

You may not qualify if:

• Presence of active infection;
• Presence of DMD-associated cardiomyopathy manifestations;
• Respiratory insufficiency requiring invasive or non-invasive ventilation;
• Serious infections such as pneumonia, pyelonephritis, or meningitis within 4 weeks prior to receiving trial drug infusion;
• Prior central nervous system surgery within 6 months before enrolment;
• Use of any investigational drug, or exon-skipping drug (whether investigational or not) 6 months prior to Screening;
• Previous treatment with any gene therapy or cell therapy (e.g., stem cell transplantation);
• Any other conditions that would not allow the potential subject to complete follow-up examinations during the study and would, in the opinion of the investigator, make the potential subject unsuitable for the study.

Sponsors & Collaborators

• HuidaGene Therapeutics Co., Ltd.: lead

Study Sites (1)

Shanghai Children s Medical Center Affiliated to Shanghai Jiao Tong University School of Medical

Shanghai, Shanghai Municipality, China

Location

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

• Study Director

  HuidaGene Therapeutics Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two dosing cohort: Low dose :2\~3 subjects High dose: 2\~3 subjects

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: November 6, 2024
• Primary Completion: December 2, 2025
• Study Completion: December 2, 2025
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)