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

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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




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


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, Shire


Verification Date

July 2019