Alpha1-antitrypsin Deficiency
Conditions
Brief summary
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.
Interventions
Sponsors
Arriva Pharmaceuticals, Inc.
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants who develop antibodies to Recombinant Alpha 1-Antitrypsin (rAAT) | 6 weeks after the first inhalation of study drug |
Countries
United States
Outcome results
None listed