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

Alpha1-antitrypsin Deficiency Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00157092
• Other study ID #: 410302
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 1, 2004
• Est. completion date: October 14, 2004

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: October 14, 2004
• Est. primary completion date: October 14, 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Alpha1-antitrypsin Deficiency

Intervention

Drug:
• Aerosolized, Recombinant Alpha 1-Antitrypsin

Locations

Country	Name	City	State
United States	Shands Hospital at the University of Florida	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Baxalta now part of Shire	Arriva Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alpha 1-antitrypsin levels assessed from epithelial lining fluid (ELF) samples		Baseline (minimum of 3 to a maximum of 4 weeks prior to the first administration of study product).
Primary	Alpha 1-antitrypsin levels assessed from epithelial lining fluid (ELF) samples		Day 8 after the first administration of study product