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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06392724
Other study ID # GATx-01-IIT-CLINC
Secondary ID
Status Not yet recruiting
Phase Early Phase 1
First received
Last updated
Start date July 2024
Est. completion date December 2027

Study information

Verified date June 2024
Source Peking Union Medical College Hospital
Contact Yi Dai
Phone +8615652018279
Email pumchdy@sohu.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 3
Est. completion date December 2027
Est. primary completion date December 2025
Accepts healthy volunteers No
Gender Male
Age group 4 Years to 10 Years
Eligibility 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: ?-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 Design


Related Conditions & MeSH terms


Intervention

Genetic:
GEN6050X intravenous injection
GEN6050X is an intravenously administered human DMD exon 50 skipping base editing drug.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Peking Union Medical College Hospital

References & 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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
Secondary 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
Secondary Physical Therapy Assessment 6MWT Change in Six-minutes Walk Test (6MWT) Screening, 6 months-3 Years
Secondary Physical Therapy Assessments Change in Time to Stand (TTSTAND) Change in Time to Stand (TTSTAND) Screening, 6 months-3 Years
Secondary Physical Therapy Assessments Ascend and Descend of 4 steps Change in Time to Climb 4 Steps Test Screening, 6 months-3 Years
Secondary 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
Secondary Physical Therapy Assessments upper limb function Change score in Performance of Upper Limb (PUL) 2.0 Screening, 6 months-3 Years
Secondary Physical Therapy Assessments Pulmonary function Change in pulmonary function test Screening, 6 months-3 Years
Secondary Dystrophin protein expression Dystrophin protein recovery level in muscle biopsy. 24 weeks post-treatment
Secondary Serum creatine kinase(CK) Decrease in CK levels in circulating blood through 1 year post-treatment
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