Gene Transfer Clinical Trial to Deliver rAAVrh74.MCK.GALGT2 for Duchenne Muscular Dystrophy

Phase 1

Active, not recruiting

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Biological: rAAVrh74.MCK.GALGT2

• Registration Number: NCT03333590
• Lead Sponsor: Kevin Flanigan

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

Study Timeline

• Study First Submitted: 2017-11-01
• Study First Submitted QC: 2017-11-03
• Study Start: 2017-11-06
• Study First Posted: 2017-11-07
• Primary Completion: 2020-11-04
• Results First Submitted: 2022-01-19
• Results First Submitted QC: 2022-04-21
• Results First Posted: 2022-04-25
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-12
• Last Update Posted: 2023-09-14
• Study Completion: 2023-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 2

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1 (Minimal Efficacious Dose) rAAVrh74.MCK.GALGT2	rAAVrh74.MCK.GALGT2	N = 3 \[2.5 x E13 vg/kg per leg, delivered bilaterally (total 5.0 x E13 vg/kg)\]
Cohort 2 (Dose Escalation) rAAVrh74.MCK.GALGT2	rAAVrh74.MCK.GALGT2	N=3 \[5 x E13 vg/kg per leg, delivered bilaterally (total 1.0 x E14 vg/kg)\]

Primary Outcome Measures

Name	Time	Method
Number of Unanticipated Grade III or Higher Treatment-Related Toxicities	2 years

Secondary Outcome Measures

Name	Time	Method
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)	Percentage of fibers expressing GALGT2 in each biopsy sample.
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)

Trial Locations

Locations (1)

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States