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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT01684410
First received: September 6, 2012
Last updated: November 26, 2013
Last verified: August 2013
  Purpose

This is 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 is intended to provide multi-dose safety information prior to proceeding to longer durations of exposure.


Condition Intervention Phase
Cystic Fibrosis
Biological: Alpha-1 HC
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    FEV1 conducted before and after inhalation of the investigational product.

  • Adverse Events [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    The number of subjects with adverse events.

  • Forced Vital Capacity (FVC) [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    FVC conducted before and after inhalation of the investigational product.


Enrollment: 41
Study Start Date: August 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alpha-1 HC 100 mg
100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.
Biological: Alpha-1 HC
Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.
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
Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.
Other Names:
  • Alpha1-proteinase inhibitor
  • alpha1-antitrypsin
Placebo Comparator: Placebo
Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate) is composed of the same elements listed for Alpha-1 HC, minus Alpha-1 HC. Polysorbate 80 at 0.01% (weight/volume) is added to mimic the foaming properties of Alpha-1 HC.
Biological: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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, 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 anytime 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684410

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 Inc.
  More Information

No publications provided

Responsible Party: Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01684410     History of Changes
Other Study ID Numbers: T6005-201
Study First Received: September 6, 2012
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Grifols Therapeutics Inc.:
Cystic Fibrosis
Alpha1-proteinase inhibitor
Alpha1-antitrypsin

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Cystic Fibrosis
Fibrosis
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Pancreatic Diseases
Infant, Newborn, Diseases
Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014