Evaluating a new gene therapy for Duchenne Muscular Dystrophy

A Single-arm, Open-label, Single-center Study to Evaluate the Safety and Tolerability of Intravenous GEN6050X Gene Therapy in Ambulatory Boys With Duchenne Muscular Dystrophy (DMD).

This study is testing a new gene therapy for boys aged 4 to 9 with Duchenne muscular dystrophy to see if it is safe and can help improve their condition.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 3 (estimated)
• Ages: 4 Years to 10 Years
• Sex: Male
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Drugs / interventions: rituximab
• Locations: 1 site (Beijing)
• Trial ID: NCT06392724 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and tolerability of GEN6050X, a gene therapy designed for boys with Duchenne muscular dystrophy (DMD) who are eligible for exon 50 skipping. The study involves a single intravenous infusion of the therapy and will monitor participants over a 52-week period for adverse events, pharmacokinetics, and preliminary clinical efficacy. It is a first-in-human, open-label trial conducted at a single center, enrolling three ambulatory boys aged 4 to 9 years. Participants will also receive a short-term immunosuppression regimen to reduce potential immune responses to the therapy.

Who should consider this trial

Good fit: Ideal candidates are ambulatory male children aged 4 to 10 years with specific DMD gene mutations amenable to exon 50 skipping.

Not a fit: Patients with active viral infections or those who do not meet the specific genetic criteria for exon 50 skipping may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option that may improve muscle function in boys with DMD.

How similar studies have performed: While this approach is novel, similar gene therapy strategies have shown promise in other studies targeting genetic disorders.

Eligibility criteria

Inclusion Criteria:

1. Subject age: 4-10 years old (including 10 years old)
2. Gender: Male
3. Patients with DMD gene exon deletion types confirmed by molecular diagnosis: 8-49, 20-49, 22-49, 51, 51-53, 51-55, 51-57, 51-59, 51-60, 51-67, 51-69, 51-75 or 51-78 and other mutations amenable to exon 50 skipping.
4. The participant is able to walk independently and completes the 10-meter walk test without assistance.
5. Participant is able to complete time to stand from supine independently in less than 30s.
6. The participant is able to cooperate with motor assessment testing.
7. Receipt of glucocorticoids for 6 months and a stable daily dose for at least 12 weeks prior to study entry
8. Ability to tolerate muscle biopsies under anesthesia with no contraindications to these procedures.

Exclusion Criteria:

1. Participants are in the active period of viral infection, including infections such as TORCH virus, Epstein-Barr(EB) virus, and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2).
2. Received a live attenuated vaccine within 3 months prior to receiving GEN6050X, or was exposed to an influenza (or other inactivated) vaccine within 30 days prior to receiving GEN6050X, or received systemic antiviral, anti-infective, and/or interferon therapy.
3. Serological tests found HIV, Hepatitis B Virus(HBV), hepatitis C virus(HCV), and syphilis infection.
4. Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks prior to receiving gene therapy.
5. With clear symptoms of cardiomyopathy, echocardiography shows that the left ventricular ejection fraction is less than 40%.
6. Need for continuous or intermittent assisted support from a ventilator.
7. Diagnosed with autoimmune disease or receiving related treatment for autoimmune disease.
8. The following indicators are abnormal in laboratory biochemical testing:

   γ-glutamyl transpeptidase (GGT) above the 2-fold upper limit and total bilirubin above 1.5 times the upper limit, cystatin C (cystatin C) \> 1.27 mg/L, hemoglobin (Hgb) \< 100 or \>200 g/L; Leukocytes (WBC) \> 18.5×10\^9/L or platelet ≤ 125×10\^9/L.
9. The titer of AAV9 neutralizing antibody determined by cell suppression assay \> 1:50.
10. Patients have received any gene therapy (e.g., adeno associated virus(AAV) gene therapy), cell therapy (e.g., stem cell transplantation), in vivo editing, or ex vivo editing therapy (e.g., CRISPR-Cas9, TALEN) in the past.
11. Participant has any contraindication to immunosuppressive therapy.
12. Has a medical condition or extenuating circumstance that, in the opinion of the principal investigator, is unsuitable for participation in the clinical trial.
13. The family does not wish to disclose the patient's study participation to the attending physician and other medical providers.

Where this trial is running

Beijing

• Peking Union Medical College Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Yi Dai

Conditions Duchenne Muscular Dystrophy; DMD; Gene therapy; Gene editing; Muscular dystrophies; Hereditary neuromuscular disorders