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
