A Study to Evaluate the Safety and Tolerability of GEN6050X in Duchenne Muscular Dystrophy.

NCT06392724 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: GATx-01-IIT-CLINC
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate the safety and tolerability of GEN6050X gene therapy in Duchenne muscular dystrophy (DMD) patients amenable to exon 50 skipping.

Conditions

Duchenne Muscular Dystrophy (DMD)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of GEN6050X measured by incidence of adverse events (AEs).

  Incidence of dose-limiting safety or intolerability, as measured by treatment-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0.

  through 1 year post-treatment

Secondary Outcomes (10)

• Physical Therapy Assessment North Star Ambulatory Assessment (NSAA）

  Screening, 6 months-3 Years

• Physical Therapy Assessment Time to run/walk 10 meters(TTRW)

  Screening, 6 months-3 Years

• Physical Therapy Assessment 6MWT

  Screening, 6 months-3 Years

• Physical Therapy Assessments Change in Time to Stand (TTSTAND)

  Screening, 6 months-3 Years

• Physical Therapy Assessments Ascend and Descend of 4 steps

  Screening, 6 months-3 Years

Study Arms (1)

GEN6050X

EXPERIMENTAL

* A single IV infusion of GEN6050X at a dose of 5×10\^13 vector genome(VG)/kg body weight * Interventions: * Genetic: GEN6050X

Genetic: GEN6050X intravenous injection

Interventions

GEN6050X intravenous injection GENETIC

GEN6050X is an intravenously administered human DMD exon 50 skipping base editing drug.

GEN6050X

Eligibility Criteria

• Age: 4 Years - 10 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject age: 4-10 years old (including 10 years old)
• Gender: Male
• 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.
• The participant is able to walk independently and completes the 10-meter walk test without assistance.
• Participant is able to complete time to stand from supine independently in less than 30s.
• The participant is able to cooperate with motor assessment testing.
• Receipt of glucocorticoids for 6 months and a stable daily dose for at least 12 weeks prior to study entry
• Ability to tolerate muscle biopsies under anesthesia with no contraindications to these procedures.

You may not qualify if:

• 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).
• 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.
• Serological tests found HIV, Hepatitis B Virus(HBV), hepatitis C virus(HCV), and syphilis infection.
• Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks prior to receiving gene therapy.
• With clear symptoms of cardiomyopathy, echocardiography shows that the left ventricular ejection fraction is less than 40%.
• Need for continuous or intermittent assisted support from a ventilator.
• Diagnosed with autoimmune disease or receiving related treatment for autoimmune disease.
• 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.
• The titer of AAV9 neutralizing antibody determined by cell suppression assay \> 1:50.
• 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.
• Participant has any contraindication to immunosuppressive therapy.
• Has a medical condition or extenuating circumstance that, in the opinion of the principal investigator, is unsuitable for participation in the clinical trial.
• The family does not wish to disclose the patient's study participation to the attending physician and other medical providers.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Related Publications (1)

• Yuan J, Ma Y, Huang T, Chen Y, Peng Y, Li B, Li J, Zhang Y, Song B, Sun X, Ding Q, Song Y, Chang X. Genetic Modulation of RNA Splicing with a CRISPR-Guided Cytidine Deaminase. Mol Cell. 2018 Oct 18;72(2):380-394.e7. doi: 10.1016/j.molcel.2018.09.002. Epub 2018 Oct 4.

  PMID: 30293782 BACKGROUND

Related Links

• Yuan J. et al. Genetic Modulation of RNA Splicing with a CRISPR-Guided Cytidine Deaminase. Mol Cell. 2018 Oct 18;72(2):380-394.e7.

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Muscular Dystrophies

Condition Hierarchy (Ancestors)

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 Design

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

Model Details: Single-arm unblinded, single-center study

Study Record Dates

• First Submitted: April 26, 2024
• First Posted: April 30, 2024
• Study Start: July 5, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 29, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)