The study will evaluate the safety and tolerability of GEN6050X gene therapy in Duchenne muscular dystrophy (DMD) patients amenable to exon 50 skipping.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
GEN6050X is an intravenously administered human DMD exon 50 skipping base editing drug.
Peking Union Medical College Hospital
Beijing, China
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.
Time frame: through 1 year post-treatment
Physical Therapy Assessment North Star Ambulatory Assessment (NSAA)
The NSAA measures the quality of ambulation in young boys with Duchenne Muscular Dystrophy.
Time frame: 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)
Time frame: Screening, 6 months-3 Years
Physical Therapy Assessment 6MWT
Change in Six-minutes Walk Test (6MWT)
Time frame: Screening, 6 months-3 Years
Physical Therapy Assessments Change in Time to Stand (TTSTAND)
Change in Time to Stand (TTSTAND)
Time frame: Screening, 6 months-3 Years
Physical Therapy Assessments Ascend and Descend of 4 steps
Change in Time to Climb 4 Steps Test
Time frame: 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.
Time frame: Screening, 6 months-3 Years
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Physical Therapy Assessments upper limb function
Change score in Performance of Upper Limb (PUL) 2.0
Time frame: Screening, 6 months-3 Years
Physical Therapy Assessments Pulmonary function
Change in pulmonary function test
Time frame: Screening, 6 months-3 Years
Dystrophin protein expression
Dystrophin protein recovery level in muscle biopsy.
Time frame: 24 weeks post-treatment
Serum creatine kinase(CK)
Decrease in CK levels in circulating blood
Time frame: through 1 year post-treatment