Clinical Trial: Gene Transfer Clinical Trial for LGMD2D (Alpha-sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Phase I/IIa Gene Transfer Clinical Trial for LGMD2D (Alpha-sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA

Brief Summary: Dose escalation study of self-complementary (sc) AAVrh74.tMCK.hSGCA delivered to single leg (low dose n=2) and bilaterally (n=6) via a major lower limb artery to the whole lower limb of limb girdle muscular dystrophy type 2D (LGMD2D; alpha-sarcoglycan deficient) patients.

Detailed Summary:

The proposed clinical trial is a dose escalation study of self-complementary scAAVrh74.tMCK.hSGCA to LGMD2D (alpha-sarcoglycan deficient) subjects delivered via a major lower limb artery of each leg sequentially by isolated limb perfusion (ILP). Three cohorts (Cohorts 1A, 1B, and 2) will undergo gene transfer in a dose escalation scheme to establish maximum tolerated dose (MTD) using toxicity. Two (n=2) adult wheelchair-dependent patients will be enrolled in Cohort 1A and three (n =3) ambulatory subjects will be enrolled in Cohort 1B. Three (n =3) ambulatory subjects will be enrolled in Cohort 2. The first cohort (1A) will receive a dose of 1E12 vg/kg in a single limb with delivery to the whole limb. This same dose will be delivered to both limbs in Cohort 1B. Cohort 2 will receive a total dose escalation of 3E12vg/kg per limb delivered to both extremities. The vector will be infused into an indwelling catheter in the femoral artery. This will be a one-time vector infusion to an isolated limb with a 10-minute dwell time. The total vector genome dose for each subject will be adjusted by rounding down to the closest 10 kg.

Safety monitoring during infusion will include: activated clotting times, limb gases, real time monitoring of arterial and venous access pressures, and perfusate temperature. Safety endpoints will be assessed by changes in hematology, serum chemistry, urinalysis, immunologic response to rAAVrh74 and hSGCA, and reported history and observations of symptoms. Efficacy will be measured by the six minute walk test as well as direct muscle testing for strength (MVICT) of lower limb muscles. These quantitative measures will be done at baseline, day 30, 60, 90, 180, and at the end of 1st and 2nd years. 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. On Day 180, subjects will un
Sponsor: Jerry R. Mendell

Current Primary Outcome: Safety with fewer than one grade 3 adverse events or fewer than two grade 2 adverse events [ Time Frame: 2 years ]

Safety will be measured based on fewer than one grade 3 adverse event or fewer than two grade 2 adverse events


Original Primary Outcome: Safety with fewer than 2 grade 3 adverse events [ Time Frame: 1 year from start ]

Safety with fewer than 2 grade 3 adverse events


Current Secondary Outcome: Change in Six-Minute-Walk-Test (6MWT) distance from baseline over two years [ Time Frame: 2 years ]

Efficacy would be a significant improvement in distance walked in the 6 minute walk test.


Original Secondary Outcome: Efficacy outcome measure 6MWT [ Time Frame: 2 years ]

6 minute walk test (6MWT)-(primary variable to measure efficacy) Efficacy would be a significant improvement in distance walked in the 6 minute walk test.


Information By: Nationwide Children's Hospital

Dates:
Date Received: July 24, 2013
Date Started: February 2015
Date Completion: February 2017
Last Updated: March 28, 2016
Last Verified: March 2016