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

Inclusion Criteria

• •1. Have a diagnosis of AAT-deficiency, as defined by a serum AAT level of less than 11 µM and a phenotype or genotype either homozygous for PI\*Z or compound heterozygous consisting of PI\*Z and another allele known to be associated with disease
• •2. Be at least 18 and not more than 75 years of age
• •3. Have a forced expiratory volume at one second (FEV1) \>25% of predicted value (post bronchodilator)
• •4. Weigh ≤ 90 kg
• •5. Not receiving AAT augmentation therapy currently or with the past 3 months, and not planning to begin such therapy for at least 12 months after administration of rAAV1-CB-hAAT
• •6. Be willing to discontinue aspirin, aspirin-containing products, and other drugs that may alter platelet function, 7 days prior to dosing, resuming no earlier than 24 hours after the dose has been administered
• •7. Have acceptable laboratory parameters:
• •* Hemoglobin ≥ 11.2 g/dL for females, ≥ 12.8 g/dL for males,
• •* White blood cell count 3,300 - 12,000 cells/mm3,
• •* Platelet count 125,000 - 550,000/mm3,
• •* Serum creatine kinase (CK) ≤ 3 times upper normal range for study laboratory,
• •* Alanine aminotransferase (ALT) ≤ 2 times upper normal range for study laboratory,
• •* Serum bilirubin ≤ 1.5 times upper normal range for study laboratory,
• •* Serum creatinine within normal range for study laboratory,
• •* Prothrombin time (PT) ≤ 14.5 seconds and partial thromboplastin time (PTT)
• •≤ 36 seconds,
• •* Normal urine dipstick (negative glucose, negative hemoglobin, and negative or trace protein),
• •8. For females of childbearing potential:
• •* A negative pregnancy test (urine or serum) at screening and at baseline (within 2 days before administration of study agent)
• •* Agreement to consistently use barrier contraception (condoms, diaphragm or cervical cap with spermicide) or another form of contraception (e.g. intrauterine device or hormonal contraception) from the screening visit until 12 months after administration of rAAV1-CB-hAAT, for sexual activity that could lead to pregnancy
• •9. For males of reproductive potential, agreement to consistently use barrier contraception (condoms with spermicide) for 12 months after administration of rAAV1-CB-hAAT, for sexual activity that could lead to pregnancy,
• •10. Provide signed informed consent before screening