Phase I/IIa Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2
Overview
- Phase
- Phase 1
- Intervention
- rAAVrh74.MCK.GALGT2
- Conditions
- Duchenne Muscular Dystrophy
- Sponsor
- Kevin Flanigan
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Number of Unanticipated Grade III or Higher Treatment-Related Toxicities
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The proposed clinical trial study of rAAVrh74.MCK.GALGT2 for duchenne muscular dystrophy (DMD) patients. There will be a modified intravascular limb infusion (ILI) procedure that will be used to sequentially deliver vector to each whole lower limb of DMD subjects via a major lower limb artery.
Detailed Description
This is an open-label, dose escalation trial where the vector will be delivered via the femoral artery to the muscles of both legs of DMD subjects. The primary objective of this study is the assessment of the safety of intravascular administration of rAAVrh74.MCK.GALGT2 to DMD patients. Safety endpoints will be assessed by changes in hematology, serum chemistry, urinalysis, immunologic response to rAAVrh74 and GALGT2, and reported history and observations of symptoms. Efficacy measures will be used as secondary outcome for this disorder including a combination of functional 6 minute walk test (6MWT) and direct muscle testing for strength (MVICT) of lower limb muscles. Subjects will be evaluated at baseline, infusion visit (days 0-2), and return for follow up visits on days 7, 14, 30, 60, 90, and 180 and months 12, 18 and 24
Investigators
Kevin Flanigan
Professor of Pediatrics
Nationwide Children's Hospital
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort 1 (Minimal Efficacious Dose) rAAVrh74.MCK.GALGT2
N = 3 \[2.5 x E13 vg/kg per leg, delivered bilaterally (total 5.0 x E13 vg/kg)\]
Intervention: rAAVrh74.MCK.GALGT2
Cohort 2 (Dose Escalation) rAAVrh74.MCK.GALGT2
N=3 \[5 x E13 vg/kg per leg, delivered bilaterally (total 1.0 x E14 vg/kg)\]
Intervention: rAAVrh74.MCK.GALGT2
Outcomes
Primary Outcomes
Number of Unanticipated Grade III or Higher Treatment-Related Toxicities
Time Frame: 2 years
Secondary Outcomes
- Expression of GALGT2 as Demonstrated by Immunofluorescent Staining With Anti-CT Epitope Antibodies or WFA Lectin in Muscle Biopsy Sections at 120 Days Post Injection (Cohort 1) and 90 Days Post-injection (Cohort 2).(Day 90 (Cohort 2) and Day 120 (Cohort 1))
- GALGT2 Protein Expression Quantified by Western Blot and Assessed by Densitometry in Muscle Biopsy Tissue at 120 Days Post-injection (Cohort 1) and 90 Days Post-injection (Cohort 2)(Day 90 (Cohort 2) and Day 120 (Cohort 1))