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