Safety and Tolerability Trial of Inhaled Alpha1-Proteinase Inhibitor (Human), Hydrophobic Chromatography Process (Alpha-1 HC) in Subjects With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Alpha-1 HC 100 mg; Placebo; Alpha-1 HC 200 mg
Intervention description: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma. Alpha-1 HC 100 mg inhaled once daily for 21 days for a total of 21 inhaled treatments.; Phosphate Buffer Saline with Polysorbate (placebo) composed of the same elements listed for Alpha-1 HC, minus the 50 mg/mL of Alpha-1 HC. Placebo inhaled once daily for 21 days for a total of 21 inhaled treatments.; Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma. Alpha-1 HC 200 mg inhaled once daily for 21 days for a total of 21 inhaled treatments.
Intervention MeSH terms: Protease Inhibitors; Alpha 1-Antitrypsin; Protein C Inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cystic Fibrosis; Alpha1-proteinase inhibitor; Alpha1-antitrypsin

Summary:

      This was a randomized, double-blind, placebo-controlled, dose escalation study to assess the
      safety and tolerability of 100 mg and 200 mg of inhaled Alpha-1 HC administered once a day
      for three weeks in subjects aged 18 years and older with cystic fibrosis (CF). The treatment
      duration in this study was intended to provide multi-dose safety information prior to
      proceeding to longer durations of exposure.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 years or older.

          -  Documentation of CF diagnosis.

          -  Have a pre-bronchodilator FEV1 ≥ 40% of predicted at Visit 1 and have a Visit 2
             pre-investigational product FEV1 that is ≥ 40% of predicted and within ± 15% of the
             Visit 1 result.

          -  Deemed by the Investigator to be a suitable candidate for serial collection of
             expectorated sputum.

        Exclusion Criteria:

          -  Had a pulmonary exacerbation during the 4 weeks before screening (Visit 1) which
             required the initiation of new antibiotic treatment

          -  Have a pulmonary exacerbation during the screening period (between Visit 1 and Visit
             2) which requires the initiation of new antibiotic treatment

          -  FEV1 < 0.59 liters at the screening visit

          -  Respiratory insufficiency with continuous supplemental oxygen therapy, or carbon
             dioxide retention

          -  Elevated aspartate transaminase (AST) or alanine aminotransferase (ALT) that is ≥ 3
             times the upper limit of normal for age and gender

          -  Smoking during the past 6 months

          -  Lung surgery during the past 2 years

          -  Positive culture for Burkholderia cepacia or mycobacterium during the past two years.

          -  Active allergic bronchopulmonary aspergillosis

          -  Pre-treatment sputum collection at Visit 1 or Visit 2 (Randomization) characterized by
             problems such as inadequate sputum volume or quality.

          -  Known selective Immunoglobulin A (IgA) deficiency with known antibody against IgA
             (anti-IgA antibody).

          -  History of anaphylaxis or severe systemic response to any plasma-derived
             alpha1-proteinase inhibitor preparation or other blood product(s), or to polysorbates.

          -  Use of chronic oral steroids during the study. Note: Inhaled corticosteroids that had
             been administered for at least 4 weeks prior to Visit 1 were permissible during the
             study.

          -  Use of chronic, high dose ibuprofen therapy within 3 weeks of screening and at anytime
             during the study.

          -  Chronic maintenance therapy with systemic antibiotics within 3 weeks of screening and
             through last dose of investigational product.

          -  Use of leukotriene synthesis inhibitor (zileuton) or leukotriene receptor antagonists
             (montelukast, zafirlukast) within 3 weeks of screening and at anytime during the
             study.

          -  Use of roflumilast within 3 weeks of screening and at any time during the study.

          -  Initiation of a new chronic medication or dosage change of a chronic medication for
             treatment of cystic fibrosis (example: Kalydeco™ [ivacaftor]) within 3 weeks of
             screening (Visit 1).