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

Baxalta

Status and phase

Completed

Phase 2

Phase 1

Conditions

Alpha1-antitrypsin Deficiency

Treatments

Drug: Aerosolized, Recombinant Alpha 1-Antitrypsin

Study type

Interventional

Funder types

Industry

Identifiers

NCT00157092

410302

Details and patient eligibility

About

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.

Enrollment

15 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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