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

NCT ID: NCT06392724

Last Updated: 2025-07-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-05
• Study Completion Date: 2027-12-31

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.

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.

Conditions

Duchenne Muscular Dystrophy (DMD)

Study Design

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

Study Groups

GEN6050X

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

• Genetic: GEN6050X

Group Type: EXPERIMENTAL

GEN6050X intravenous injection

Intervention Type: GENETIC

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

Interventions

GEN6050X intravenous injection

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

Intervention Type: GENETIC

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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yi Dai

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Peking Union Medical College Hospital

Beijing, , China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 30293782 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/30293782/

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.

Other Identifiers

GATx-01-IIT-CLINC

Identifier Type: -

Identifier Source: org_study_id