Safety and Tolerability Trial of Inhaled Alpha1-Proteinase Inhibitor (Human), Hydrophobic Chromatography Process (Alpha-1 HC) in Subjects With Cystic Fibrosis

Study Overview
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Brief Summary
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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.

Official Title
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A Three Week Dose Escalation, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety and Tolerability of 100 mg or 200 mg of Inhaled Alpha-1 HC, Once a Day in Subjects With Cystic Fibrosis.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Biological: Alpha-1 HC 100 mg
* Biological: Placebo
* Biological: Alpha-1 HC 200 mg


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alpha-1 HC 100 mg<br>100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks. | Biological: Alpha-1 HC 100 mg<br>* 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.<br>* Other names: alpha1-antitrypsin;|
| Experimental: Alpha-1 HC 200 mg<br>200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks. | Biological: Alpha-1 HC 200 mg<br>* 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.<br>* Other names: alpha1-antitrypsin;|
| Placebo Comparator: Placebo<br>Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate). | Biological: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | adverse event frequency | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Alpha1-proteinase inhibitor, Alpha1-antitrypsin