Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation"
Condition: Alpha-1 Antitrypsin Deficiency
MeSH terms: Alpha 1-Antitrypsin Deficiency
Intervention: Kamada-AAT for Inhalation, 80mg; Placebo; Kamada-AAT for Inhalation, 160mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      To evaluate different doses of "Kamada-AAT for Inhalation" on the levels of alpha
      1-proteinase inhibitor and other analytes in epithelial lining fluid (ELF) and serum and to
      assess the safety of the treatment in subjects with AAT Deficiency.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients between 18 and 65 years of age (inclusive).

          -  Able and willing to sign informed consent.

          -  Males, and non-pregnant, non-lactating females whose screening pregnancy test is
             negative and who are using contraceptive methods deemed reliable by the investigator
             or who are post-menopausal or surgically sterilized.

          -  Diagnosis of alpha1-antitrypsin deficiency [only individuals with a ZZ or Z null
             classification].

          -  Forced expiratory volume in one second (FEV1) ≥ 50% of predicted post bronchodilator

          -  No respiratory exacerbations within 6 weeks of baseline. Subjects can be re-screened
             if exacerbations exist at the time of enrollment.

          -  No signs of chronic and/or acute Hepatitis A, Hepatitis B, Hepatitis C, HIV infection
             and Parvovirus B19, by NAT (for Parvovirus B19, nucleic acid testing (NAT) result must
             be < 10^4 IU/mL).

          -  No significant abnormalities in serum hematology, serum chemistry, serum inflammatory
             / immunogenic markers and urinalysis.

          -  No significant abnormalities in ECG.

          -  Not on intravenous augmentation therapy for at least 8 weeks prior to initial dosing
             with study drug/placebo and willing to forego intravenous augmentation therapy for the
             duration of the study.

        Exclusion Criteria:

          -  Clinically significant intercurrent illnesses (except for respiratory or liver disease
             secondary to AAT deficiency), including: cardiac, hepatic, renal, endocrine,
             neurological, hematological, neoplastic, immunological, skeletal or other) that in the
             opinion of the investigator, could interfere with the safety, compliance or other
             aspects of this study. Patients with well-controlled, chronic diseases could possibly
             be included after consultation with the treating physician and the sponsor.

          -  History of life threatening allergy, anaphylactic reaction, or systemic response to
             human plasma derived products.

          -  History of life threatening transfusion reactions.

          -  History of lung transplant.

          -  Current or previous (up to 8 weeks from baseline) use of AAT augmentation therapy or
             by any other route

          -  Current use of oral or parenteral glucocorticoids in doses exceeding 10mg of
             prednisone daily or equivalent generics (substance and dose).

          -  Any lung surgery within the past two years.

          -  On any thoracic surgery waiting list.

          -  Active smoking during the last 12 months from screening date.

          -  Pregnancy or lactation.

          -  Woman of child-bearing potential not taking adequate contraception deemed reliable by
             the investigator.

          -  Presence of psychiatric/ mental disorder or any other medical disorder which might
             impair the patient's ability to give informed consent or to comply with the
             requirements of the study protocol.

          -  Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally
             prescribed drugs.

          -  Immunoglobulin A (IgA) Deficiency.

          -  Inability to undergo bronchoscopy.

          -  Allergy to lidocaine or any other medicines used in the bronchoscopy process

          -  Exacerbation of chronic obstructive pulmonary disease (COPD) in the previous 6 weeks.

          -  Participation in another clinical trial involving investigational medication or
             interventional treatment within 30 days prior to baseline visit.

          -  Participation in observational clinical trial which involves any invasive procedure
             scheduled to occur during the AAT inhaled study period. If participating in an
             observational clinical trial that already completed all diagnostic procedures (e.g.
             liver biopsy), any adverse events (AEs) experienced must have returned to baseline
             within 30 days prior to baseline visit.

          -  Inability to attend scheduled clinic visits and/or comply with the study protocol.

          -  Any other factor that, in the opinion of the investigator, would prevent the patient
             form complying with the requirements of the protocol.