Clinical trial NCT01684410: Safety and Tolerability Trial of Inhaled Alpha1-Proteinase Inhibitor (Human), Hydrophobic Chromatography Process (Alpha-1 HC) in Subjects With Cystic Fibrosis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Alpha1-proteinase inhibitor
Alpha1-antitrypsin
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2012-09-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Adverse Events
timeFrame: 3 weeks
Secondary outcomes:
Other outcomes:
measure: Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 3
timeFrame: 3 weeks
measure: Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 3
timeFrame: 3 weeks
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Denver
country: United States
facility: National Jewish Hospital
state: Colorado
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Chapel Hill
country: United States
facility: UNC at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References: