Study of the Effect of Aerosolized, Recombinant Alpha 1-Antitrypsin on Epithelial Lining Fluid Analytes in Subjects With Alpha 1-Antitrypsin Deficiency

This study has been completed.
Arriva Pharmaceuticals, Inc.
Information provided by:
Baxalta US Inc. Identifier:
First received: September 8, 2005
Last updated: June 26, 2015
Last verified: October 2006
The study was a Phase 1B/2A, uncontrolled, open-label, single-center study in individuals with congenital AAT (alpha 1-antitrypsin) deficiency. A baseline bronchoscopy with bronchoalveolar lavage (BAL) was performed 3 to a maximum of 4 weeks prior to the first administration of study drug. Fifteen eligible subjects were randomized to receive 1 of 3 dosing regimens of rAAT (100 mg daily, 100 mg twice daily, or 200 mg daily) administered via nebulization for 7 consecutive days. A post-treatment nadir BAL was obtained on study Day 8 (12 hours after last dose for subjects who receive drug therapy twice daily and 24 hours after the last dose for subjects who receive study product daily). BALs were conducted in the same lung lobe/segment. Follow-up visits took place on Day 15 and Day 36.

Condition Intervention Phase
Alpha 1-Antitrypsin Deficiency
Drug: Aerosolized, Recombinant Alpha 1-Antitrypsin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1B/2A Study to Evaluate the Effect of Aerosolized, Recombinant Alpha 1-Antitrypsin on Epithelial Lining Fluid Analytes in Subjects With Alpha 1-Antitrypsin Deficiency

Resource links provided by NLM:

Further study details as provided by Baxalta US Inc.:

Estimated Enrollment: 15
Study Start Date: March 2004
Estimated Study Completion Date: October 2004

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed Informed Consent
  • Male or female 18 years of age or older
  • Documented, endogenous plasma AAT levels < 11 µM (< 80 mg/dL), either obtained from the medical history or, if not documented, plasma AAT measured after 28 day washout of any prior replacement therapy
  • Forced expiratory volume at 1 second (FEV1) that is >= 50% of predicted, measured 30 minutes after a short-acting inhaled bronchodilator
  • Arterial oxygen percent saturation (SaO2, measured using room air) within the normal limits for the individual study site
  • For subjects receiving an inhaled corticosteroid, inhaled or oral β-2 agonist (e.g., albuterol via metered dose inhaler [MDI]) or inhaled anticholinergic bronchodilator (e.g., ipratropium bromide), or oral PDE (phosphodiesterase) inhibitor, treatment on a stable dose for at least 14 days prior to enrollment
  • For any female of childbearing potential, a negative urine test for pregnancy within 3 days prior to enrollment and agreement to employ adequate birth control measures for the duration of the study
  • No clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed at the screening visit
  • Laboratory results obtained at the screening visit, 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

Exclusion Criteria:

  • Clinically significant pulmonary impairment, other than emphysema and/or chronic bronchitis
  • Moderate to severe bronchiectasis
  • 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 within 28 days prior to the screening visit
  • 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
  • Prior history of adverse reactions to the local anesthetic, sedative, BAL procedure, or pre-medication employed at the study center
  • Use of oral or parenteral glucocorticosteroids, or alpha 1-antitrypsin replacement therapy within 28 days prior to baseline BAL, or any use planned during the study. However, the subject may enroll provided that a) consent is given to undergo a 28-day washout of the replacement or steroid therapy, and b) no study procedures are done until the washout is completed.
  • Use of another investigational drug or investigational device within 28 days prior to baseline BAL
  • Any upper or lower respiratory infection within 28 days prior to baseline BAL
  • Having received a lung or liver transplant
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Please refer to this study by its identifier: NCT00157092

United States, Florida
Shands Hospital at the University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
Baxalta US Inc.
Arriva Pharmaceuticals, Inc.
Principal Investigator: Mark Brantly, MD University of Florida, Shands Hospital
  More Information Identifier: NCT00157092     History of Changes
Other Study ID Numbers: 410302 
Study First Received: September 8, 2005
Last Updated: June 26, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Digestive System Diseases
Genetic Diseases, Inborn
Liver Diseases
Lung Diseases
Pathologic Processes
Respiratory Tract Diseases
Subcutaneous Emphysema
Alpha 1-Antitrypsin
Protein C Inhibitor
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Trypsin Inhibitors processed this record on May 03, 2016