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.

Study Overview

• Status: Completed
• Conditions: Alpha1-antitrypsin Deficiency
• Intervention / Treatment: Drug: Aerosolized, Recombinant Alpha 1-Antitrypsin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • Shands Hospital at the University of Florida
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation, Department of Pulmonary and Critical Care Medicine
  • Texas
    • Tyler, Texas, United States, 75708-3154
      • The University of Texas Health Science Center at Tyler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants who develop antibodies to Recombinant Alpha 1-Antitrypsin (rAAT)	6 weeks after the first inhalation of study drug

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Arriva Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2003
• Primary Completion (Actual): October 1, 2003
• Study Completion (Actual): October 1, 2003

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 13, 2005

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Alpha 1-Antitrypsin; Protein C Inhibitor
• Other Study ID Numbers: 410103