Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency

The question of whether higher doses of Alpha-1 PI (>60 mg/kg) are able to provide better
protection to patients with alpha 1-antitrypsin deficiency is currently unknown. As a first
step to address this question, the present study has been undertaken. This is a
multi-center, randomized, double-blind, crossover study to assess the safety and
pharmacokinetics of weekly infusions of 120 mg/kg of Alpha-1 PI, compared to weekly
infusions of 60 mg/kg of Alpha-1 PI in patients with alpha 1-antitrypsin deficiency. This
study is a crossover design with 2 treatment sequences:

Treatment Sequence 1: 60 mg/kg weekly infusion of Alpha-1 PI for 8 weeks followed by 120
mg/kg weekly infusion of Alpha-1 PI for 8 weeks (starting at Week 1) (total of 16 treatment
weeks)

Treatment Sequence 2: 120 mg/kg weekly infusion of Alpha-1 PI for 8 weeks followed by 60
mg/kg weekly infusion of Alpha-1 PI for 8 weeks (starting at Week 11) (total of 16 treatment
weeks)

Approximately 15 subjects are planned to be entered into each treatment sequence.

At Weeks 8 to 11 and Weeks 18 to 21, a total of 15 serial blood samples for each subject
will be drawn for pharmacokinetic analysis. The expected duration of the study subject's
participation will be approximately 25 weeks (which includes a 3-Week Screening Phase,
2-Week Washout Period [between different alpha-1 PI treatment doses], and a 4-Week Follow-up
Period). The following safety parameters will be assessed: adverse events, pulmonary
exacerbations, vital signs, pulmonary function tests, and clinical laboratory tests.