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

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.

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Biological: Alpha-1 HC 100 mg; Biological: Alpha-1 HC 200 mg; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC at Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alpha-1 HC 100 mg; 100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.	Biological: Alpha-1 HC 100 mg; 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.; Other Names: Alpha1-proteinase inhibitor; alpha1-antitrypsin
Experimental: Alpha-1 HC 200 mg; 200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.	Biological: Alpha-1 HC 200 mg; 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.; Other Names: Alpha1-proteinase inhibitor; alpha1-antitrypsin
Placebo Comparator: Placebo; Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).	Biological: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 3	FEV1 conducted before and after inhalation of the investigational product at study visits.	3 weeks
Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 3	FVC conducted before and after inhalation of the investigational product	3 weeks

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: September 6, 2012
• First Submitted That Met QC Criteria: September 10, 2012
• First Posted (Estimate): September 13, 2012

Study Record Updates

• Last Update Posted (Estimate): February 8, 2016
• Last Update Submitted That Met QC Criteria: January 11, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Alpha1-proteinase inhibitor; Alpha1-antitrypsin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Protease Inhibitors; Alpha 1-Antitrypsin; Protein C Inhibitor
• Other Study ID Numbers: T6005-201