Clinical trial NCT00161707: Safety Study of an Aerosolized, Recombinant Alpha 1-Antitrypsin in Subjects With Alpha 1-Antitrypsin Deficiency
Official title: Phase I Safety Investigation of an Aerosolized, Recombinant Alpha 1-Antitrypsin in Subjects With Alpha 1-Antitrypsin Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alpha1-antitrypsin Deficiency
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Arriva Pharmaceuticals, Inc.
First posted: 2005-09-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants who develop antibodies to Recombinant Alpha 1-Antitrypsin (rAAT)
timeFrame: 6 weeks after the first inhalation of study drug
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Gainesville
country: United States
facility: Shands Hospital at the University of Florida
state: Florida
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation, Department of Pulmonary and Critical Care Medicine
state: Ohio
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: