Safety Study of an Aerosolized, Recombinant Alpha 1-Antitrypsin in Subjects With Alpha 1-Antitrypsin Deficiency

Phase I Safety Investigation of an Aerosolized, Recombinant Alpha 1-Antitrypsin in Subjects With Alpha 1-Antitrypsin Deficiency

The purpose of this randomized, double-blind, placebo-controlled study is to evaluate the short-term safety of inhaled recombinant alpha 1-antitrypsin (rAAT) in subjects with alpha 1-antitrypsin deficiency. The subjects are randomized to receive placebo or one of 4 doses of rAAT. The 4 doses are tested in a consecutive manner from lowest to highest.

Inclusion Criteria:

• Male or female 18 years of age or older
• Endogenous plasma AAT levels < 11 µM (< 80 mg/dL)
• Baseline forced expiratory volume at one second (FEV1) that is >= 50% of predicted, measured 30 minutes after a short-acting inhaled bronchodilator
• Baseline arterial oxygen percent saturation (SaO2) within the normal limits for the individual study site
• For subjects receiving an inhaled corticosteroid, β-2 agonist (eg, albuterol via metered dose inhaler [MDI]) or anticholinergic bronchodilator (eg, ipratropium bromide), treatment on a stable dose for at least 14 days prior to randomization
• If female of childbearing potential, negative urine pregnancy test within 3 days prior to randomization and agreement to employ adequate birth control measures
• No clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed no more than 7 days prior to randomization
• Baseline laboratory results, obtained no more than 7 days prior to randomization, meeting the following criteria:
• Serum aspartate transaminase (AST) and alanine transaminase (ALT) <= 2 times upper limit of normal range (ULN)
• Serum total bilirubin <= 2 times ULN
• < 2+ proteinuria on urine dipstick
• Serum creatinine <= 1.5 times ULN
• Absolute neutrophil count >= 1500 cells/mm3
• Hemoglobin >= 10.0 g/dL
• Platelet count >= 100,000/mm3
• Signed informed consent

Exclusion Criteria:

• Clinically significant pulmonary impairment, other than emphysema and/or chronic bronchitis
• Clinically significant cardiac, hemostatic, or neurologic impairment, or other significant medical condition that, in the opinion of the investigator, would affect subject safety or compliance
• Psychiatric or cognitive disturbance or illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
• Acute exacerbation of emphysema (as defined in Section 8.5.10) within 28 days prior to randomization
• Pregnancy or lactation
• Known history of allergy to yeast products
• Medical history precluding the use of epinephrine or other rescue medication for treatment of anaphylaxis
• Use of antihistamines within 7 days prior to randomization
• Use of oral steroids, beta-blockers, or tricyclic antidepressants within 28 days prior to randomization
• Use of another investigational drug or investigational device within 28 days prior to randomization
• Any upper or lower respiratory infection within 28 days prior to randomization