A Study to Evaluate the Safety and Tolerability of GEN6050X in Duchenne Muscular Dystrophy.
- Conditions
- Duchenne Muscular Dystrophy (DMD)
- Interventions
- Genetic: GEN6050X intravenous injection
- Registration Number
- NCT06392724
- Lead Sponsor
- Peking Union Medical College Hospital
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 3
- 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.
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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).
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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.
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Serological tests found HIV, Hepatitis B Virus(HBV), hepatitis C virus(HCV), and syphilis infection.
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Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks prior to receiving gene therapy.
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With clear symptoms of cardiomyopathy, echocardiography shows that the left ventricular ejection fraction is less than 40%.
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Need for continuous or intermittent assisted support from a ventilator.
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Diagnosed with autoimmune disease or receiving related treatment for autoimmune disease.
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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.
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The titer of AAV9 neutralizing antibody determined by cell suppression assay > 1:50.
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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.
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Participant has any contraindication to immunosuppressive therapy.
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Has a medical condition or extenuating circumstance that, in the opinion of the principal investigator, is unsuitable for participation in the clinical trial.
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The family does not wish to disclose the patient's study participation to the attending physician and other medical providers.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description GEN6050X GEN6050X intravenous injection * A single IV infusion of GEN6050X at a dose of 5×10\^13 vector genome(VG)/kg body weight * Interventions: * Genetic: GEN6050X
- Primary Outcome Measures
Name Time Method Safety and tolerability of GEN6050X measured by incidence of adverse events (AEs). through 1 year post-treatment 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.
- Secondary Outcome Measures
Name Time Method Physical Therapy Assessments upper limb function Screening, 6 months-3 Years Change score in Performance of Upper Limb (PUL) 2.0
Physical Therapy Assessments Pulmonary function Screening, 6 months-3 Years Change in pulmonary function test
Physical Therapy Assessment 6MWT Screening, 6 months-3 Years Change in Six-minutes Walk Test (6MWT)
Physical Therapy Assessments Change in Time to Stand (TTSTAND) Screening, 6 months-3 Years Change in Time to Stand (TTSTAND)
Physical Therapy Assessment Time to run/walk 10 meters(TTRW) Screening, 6 months-3 Years Change in Time to Run/Walk 10 Meters Test (TTRW)
Physical Therapy Assessment North Star Ambulatory Assessment (NSAA） Screening, 6 months-3 Years The NSAA measures the quality of ambulation in young boys with Duchenne Muscular Dystrophy.
Serum creatine kinase(CK) through 1 year post-treatment Decrease in CK levels in circulating blood
Physical Therapy Assessments Ascend and Descend of 4 steps Screening, 6 months-3 Years Change in Time to Climb 4 Steps Test
Physical Therapy Assessments Hand-held dynamometer Screening, 6 months-3 Years 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.
Dystrophin protein expression 24 weeks post-treatment Dystrophin protein recovery level in muscle biopsy.
Trial Locations
- Locations (1)
Peking Union Medical College Hospital
🇨🇳Beijing, China