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

Cystic Fibrosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01684410
• Other study ID #: T6005-201
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2012
• Last updated: January 11, 2016
• Start date: August 2012
• Est. completion date: October 2013

Study information

• Verified date: January 2016
• Source: Grifols Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Cystic Fibrosis
• Fibrosis

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Children's Hospital Boston	Boston	Massachusetts
United States	UNC at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	National Jewish Hospital	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Other	Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 3	FVC conducted before and after inhalation of the investigational product	3 weeks	Yes
Primary	Adverse Events	adverse event frequency	3 weeks	Yes