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

• ClinicalTrials.gov Identifier: NCT01684410
• Recruitment Status: Completed
• First Posted: September 13, 2012
• Results First Posted: February 8, 2016
• Last Update Posted: February 8, 2016
• Sponsor: Grifols Therapeutics LLC
• Information provided by (Responsible Party): Grifols Therapeutics LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Biological: Alpha-1 HC 100 mg; Biological: Placebo; Biological: Alpha-1 HC 200 mg	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: August 2012
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: October 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Adverse Events [ Time Frame: 3 weeks ]
   adverse event frequency

Other Outcome Measures:

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

Eligibility Criteria

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

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).

Contacts and Locations

Locations

United States, Alabama

The University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, Colorado

National Jewish Hospital

Denver, Colorado, United States, 80206

United States, Massachusetts

Children's Hospital Boston

Boston, Massachusetts, United States, 02115

United States, North Carolina

UNC at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States, 44106

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Grifols Therapeutics LLC

More Information

• Responsible Party: Grifols Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT01684410
• Other Study ID Numbers: T6005-201
• First Posted: September 13, 2012
• Results First Posted: February 8, 2016
• Last Update Posted: February 8, 2016
• Last Verified: January 2016

Keywords provided by Grifols Therapeutics LLC:

Cystic Fibrosis; Alpha1-proteinase inhibitor; Alpha1-antitrypsin

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Protease Inhibitors; Alpha 1-Antitrypsin; Protein C Inhibitor; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Trypsin Inhibitors; Serine Proteinase Inhibitors