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

NCT00161707 | Completed Phase 1

• 1 other identifier: 410103
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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.

Conditions

Alpha1-antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• Number of participants who develop antibodies to Recombinant Alpha 1-Antitrypsin (rAAT)

  6 weeks after the first inhalation of study drug

Interventions

Aerosolized, Recombinant Alpha 1-Antitrypsin DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Arriva Pharmaceuticals, Inc.: collaborator

Study Sites (4)

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Shands Hospital at the University of Florida

Gainesville, Florida, 32610, United States

Location

Cleveland Clinic Foundation, Department of Pulmonary and Critical Care Medicine

Cleveland, Ohio, 44195, United States

Location

The University of Texas Health Science Center at Tyler

Tyler, Texas, 75708-3154, United States

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 13, 2005
• Study Start: January 7, 2003
• Primary Completion: October 1, 2003
• Study Completion: October 1, 2003
• Last Updated: May 5, 2021

Record last verified: 2021-04

Locations

US (4)