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) (MUSCLE)

An Investigator-initiated Clinical Study Evaluating the CRISPR-hfCas12Max Gene Editing Therapy in the Treatment of Duchenne Muscular Dystrophy (DMD)

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophin (DMD)
• Intervention / Treatment: Genetic: HG302

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai Children s Medical Center Affiliated to Shanghai Jiao Tong University School of Medical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HG302; The study will enroll up to 2 dose cohorts	Genetic: HG302; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of systemic adverse events	Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in percentage of dystrophin positive fiber	Test percentage of dystrophin positive fiber to detection of dystrophin expression	26 weeks
Change from baseline in dystrophin fiber intensity	Test dystrophin fiber intensity to detection of dystrophin expression	26 weeks
Change from baseline in North Star Ambulatory Assessment scale	North Star Ambulatory Assessment scale documents motor performance in children, with total score range from 0-34, the higher score means better motor performance	26 weeks

Collaborators and Investigators

• Sponsor: HuidaGene Therapeutics Co., Ltd.
• Investigators: Study Director: Study Director, HuidaGene Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2024
• Primary Completion (Actual): December 2, 2025
• Study Completion (Actual): December 2, 2025

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: DMD; CRISPR; dystrophin; Gene-editing; HG302
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: HG30201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We did not plan to share any IPD with other researchers, any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No