Brief Title
Study of the Effect of Aerosolized, Recombinant Alpha 1-Antitrypsin on Epithelial Lining Fluid Analytes in Subjects With Alpha 1-Antitrypsin Deficiency
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
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) 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Alpha 1-antitrypsin levels assessed from epithelial lining fluid (ELF) samples
Condition
Alpha1-antitrypsin Deficiency
Intervention
Aerosolized, Recombinant Alpha 1-Antitrypsin
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
15
Start Date
March 1, 2004
Completion Date
October 14, 2004
Primary Completion Date
October 14, 2004
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Study Director, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00157092
Organization ID
410302
Responsible Party
Sponsor
Study Sponsor
Baxalta now part of Shire
Collaborators
Arriva Pharmaceuticals, Inc.
Study Sponsor
Study Director, Study Director, Takeda
Verification Date
April 2021