Status:

COMPLETED

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

Lead Sponsor:

Baxalta now part of Shire

Collaborating Sponsors:

Arriva Pharmaceuticals, Inc.

Conditions:

Alpha1-antitrypsin Deficiency

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

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...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

March 1 2004

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 14 2004

Estimated Enrollment :

15 Patients enrolled

Trial Details

Trial ID

NCT00157092

Start Date

March 1 2004

End Date

October 14 2004

Last Update

May 5 2021

Active Locations (1)

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Page 1 of 1 (1 locations)

1

Shands Hospital at the University of Florida

Gainesville, Florida, United States, 32610