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)

NCT ID: NCT06594094

Last Updated: 2024-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-06
• Study Completion Date: 2026-09-30

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)

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HG302

The study will enroll up to 2 dose cohorts

Group Type: EXPERIMENTAL

HG302

Intervention Type: 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.

Interventions

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.

Intervention Type: GENETIC

Eligibility Criteria

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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 8 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

HuidaGene Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

HuidaGene Therapeutics Co., Ltd.

Locations

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

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Study Director

Role: CONTACT

HG30201@huidagene.com

732-318-9873

Facility Contacts

Jiwen Wang, PhD

Role: primary

wangjiwen@scmc.com.cn

+86 021-38626161

Other Identifiers

HG30201

Identifier Type: -

Identifier Source: org_study_id