Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency

2014-07-24 14:10:13 | BioPortfolio


This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector expressing alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency. Three groups of three subjects each will receive the study drug by intramuscular injection, with progressively larger doses in the second and third groups.


The study is a non-randomized, open-label, multi-center, sequential, three-arm, Phase 2 clinical trial evaluating the safety and efficacy of administration of a rAAV1-CB-hAAT vector administered by IM injection. Each participant will receive rAAV1-CB-hAAT on a single occasion. Three groups of three subjects each will receive rAAV1-CB-hAAT at dosage levels of 6 x 10e11 vg/kg, 1.9 x 10e12 vg/kg or 6 x 10e12 vg/kg by IM injection. Subjects in group 1 will receive a total of 10 IM injections distributed across a single muscle site, subjects in group 2 will receive a total of 32 IM injections distributed across three muscle sites, and subjects in group 3 will receive 100 IM injections distributed across 10 muscle sites. Each injection will be given in a volume of 1.35 mL, at the appropriate vector concentration to achieve the desired total vector dose, and the injection density at each administration site (nine IM injections per 4 cm2 skin surface area) will be the same as the injection density that was well tolerated in a previous Phase 1 clinical trial with rAAV1-CB-hAAT. Safety will be monitored by evaluation of adverse events, hematology and clinical chemistry parameters, histological examination of muscle biopsies, and measurement of serum antibodies to AAT. Efficacy will be measured by evaluation of serum concentrations of M-specific AAT and total AAT and serum AAT phenotype determined on isoelectric focusing gels. Additional information to be collected will include presence of the vector in blood or semen, changes in serum anti-AAV antibody titers, and changes in T cell responses to AAV and AAT.

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Alpha-1 Antitrypsin Deficiency




National Jewish Health
United States




Applied Genetic Technologies Corp

Results (where available)

View Results


Published on BioPortfolio: 2014-07-24T14:10:13-0400

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