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

Phase 2

Completed

• Conditions: Cystic Fibrosis
• Interventions: Biological: Alpha-1 HC 200 mg; Biological: Placebo; Biological: Alpha-1 HC 100 mg

• Registration Number: NCT01684410
• Lead Sponsor: Grifols Therapeutics LLC

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-09-06
• Study First Submitted QC: 2012-09-10
• Study First Posted: 2012-09-13
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Results First Submitted: 2015-08-10
• Status Verified: 2016-01
• Results First Submitted QC: 2016-01-11
• Last Update Submitted: 2016-01-11
• Results First Posted: 2016-02-08
• Last Update Posted: 2016-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alpha-1 HC 200 mg	Alpha-1 HC 200 mg	200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.
Placebo	Placebo	Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).
Alpha-1 HC 100 mg	Alpha-1 HC 100 mg	100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Primary Outcome Measures

Name	Time	Method
Adverse Events	3 weeks	adverse event frequency

Trial Locations

Locations (6)

The University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

UNC at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Children's Hospital Boston; 🇺🇸 Boston, Massachusetts, United States

Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

National Jewish Hospital; 🇺🇸 Denver, Colorado, United States