A Study to Evaluate the Safety and Tolerability of GEN6050X in Duchenne Muscular Dystrophy. (GEN6050XIIT)

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).

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

Study Overview

• Status: Active, not recruiting
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Genetic: GEN6050X intravenous injection

Detailed Description

GEN6050X is an intravenously administered human DMD exon 50 skipping base editing drug containing dual single-stranded adeno-associated virus serotype 9 (ss.AAV9) vectors.

The study is a first-in-human, single-arm, open-label, single-center clinical trial to evaluate safety and tolerability of a single intravenous infusion of GEN6050X in ambulatory boys with DMD. Other objectives include pharmacokinetics, pharmacodynamics, and the preliminary clinical efficacy of GEN6050X over 52 weeks. A total of three ambulatory pediatric participants (aged 4 to 9 years old) are expected to enroll, each receiving a dose of 5×10^13 vg/kg. These participants will be dosed in a staggered fashion.

Safety assessments will include monitoring of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations throughout the study duration. In addition, a comprehensive short-term prophylactic immunosuppression regimen(including rituximab and sirolimus) will be administered prior to treatment in order to mitigate potential immune response.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GEN6050X; 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; GEN6050X is an intravenously administered human DMD exon 50 skipping base editing drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Therapy Assessment North Star Ambulatory Assessment (NSAA）	The NSAA measures the quality of ambulation in young boys with Duchenne Muscular Dystrophy.	Screening, 6 months-3 Years
Physical Therapy Assessment Time to run/walk 10 meters(TTRW)	Change in Time to Run/Walk 10 Meters Test (TTRW)	Screening, 6 months-3 Years
Physical Therapy Assessment 6MWT	Change in Six-minutes Walk Test (6MWT)	Screening, 6 months-3 Years
Physical Therapy Assessments Change in Time to Stand (TTSTAND)	Change in Time to Stand (TTSTAND)	Screening, 6 months-3 Years
Physical Therapy Assessments Ascend and Descend of 4 steps	Change in Time to Climb 4 Steps Test	Screening, 6 months-3 Years
Physical Therapy Assessments Hand-held dynamometer	The force generated for each muscle strength (elbow extension, elbow flexion, knee extension, and knee flexion on the dominant side only) will be measured by Hand-held dynamometer.	Screening, 6 months-3 Years
Dystrophin protein expression	Dystrophin protein recovery level in muscle biopsy.	24 weeks post-treatment
Physical Therapy Assessments upper limb function	Change score in Performance of Upper Limb (PUL) 2.0	Screening, 6 months-3 Years
Physical Therapy Assessments Pulmonary function	Change in pulmonary function test	Screening, 6 months-3 Years
Serum creatine kinase(CK)	Decrease in CK levels in circulating blood	through 1 year post-treatment

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 26, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 24, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy; DMD; Gene therapy; Gene editing; Muscular dystrophies; Hereditary neuromuscular disorders
• 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; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: GATx-01-IIT-CLINC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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