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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multiple-Site, Phase 2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Alpha-1 Antitrypsin (rAAV1-CB-hAAT) in Patients With Alpha-1 Antitry

Brief Summary:

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.

Funding Sources - FDA OOPD and NIH NHLBI

Detailed Summary: 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.
Sponsor: Applied Genetic Technologies Corp

Current Primary Outcome: Frequency of Grade 3 or 4 Adverse Events [ Time Frame: During 1 year after study agent administration ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Changes in Serum M-specific Alpha-1 Antitrypsin Concentration [ Time Frame: During months 6-12 after study agent adminsitration ]
  The change in serum M-specific alpha-1 antitrypsin concentration was calculated as the difference between the mean values at the screening and baseline visits and the mean values at the 6, 9 and 12 month visits. The standard error of the difference was calculated as sqrt(s1^2/n1 + s2^2/n2, where s1 is the standard deviation of the baseline mean, s2 is the standard deviation of the month 6-12 mean, n1 is the number of baseline values and n2 is the number of month 6-12 values.
• Changes in Serum Total Alpha-1 Antitrypsin Concentrations [ Time Frame: During months 6-12 after study agent adminstration ]
  The change in serum total alpha-1 antitrypsin concentration was calculated as the difference between the mean values at the screening and baseline visits and the mean values at the 6, 9 and 12 month visits. The standard error of the difference was calculated as sqrt(s1^2/n1 + s2^2/n2, where s1 is the standard deviation of the baseline mean, s2 is the standard deviation of the month 6-12 mean, n1 is the number of baseline values and n2 is the number of month 6-12 values.

Original Secondary Outcome:

• Changes in Serum M-specific Alpha-1 Antitrypsin Concentration [ Time Frame: During months 6-12 after study agent adminsitration ]
• Changes in Serum Total Alpha-1 Antitrypsin Concentrations [ Time Frame: During months 6-12 after study agent adminstration ]

Dates:
Date Received: January 21, 2010
Date Started: March 2010
Date Completion:
Last Updated: July 13, 2016
Last Verified: July 2016