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

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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:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Biological: Alpha-1 HC 100 mg
Biological: Placebo
Biological: Alpha-1 HC 200 mg
Enrollment 30
Recruitment Details A total of 41 subjects provided informed consent and were screened for the study. Eleven (11) subjects were screen failures, and a total of 30 subjects were randomized to one of three treatment groups: 200 mg or 100 mg of Alpha-1 HC or placebo daily.
Pre-assignment Details  
Arm/Group Title Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Hide Arm/Group Description

100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).

Placebo

Period Title: Overall Study
Started 10 10 10
Completed 10 10 10
Not Completed 0 0 0
Arm/Group Title Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo Total
Hide Arm/Group Description

100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 10 10 10 30
Hide Baseline Analysis Population Description
Intent-To-Treat (ITT) Population: included all subjects who were randomized (included those withdrawn from treatment for any reason).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 10 participants 30 participants
28.2  (10.62) 28.1  (11.43) 29.3  (9.96) 28.5  (10.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
Female
8
  80.0%
6
  60.0%
6
  60.0%
20
  66.7%
Male
2
  20.0%
4
  40.0%
4
  40.0%
10
  33.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 10 participants 30 participants
10 10 10 30
1.Primary Outcome
Title Adverse Events
Hide Description adverse event frequency
Time Frame 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: included all subjects who received any dose of IP (included those withdrawn from treatment for any reason)
Arm/Group Title Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Hide Arm/Group Description:

100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).

Placebo

Overall Number of Participants Analyzed 10 10 10
Measure Type: Number
Unit of Measure: percentage of participants
100 80 60
2.Other Pre-specified Outcome
Title Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 3
Hide Description FEV1 conducted before and after inhalation of the investigational product at study visits.
Time Frame 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: included all subjects who received any dose of Investigational Product (included those withdrawn from treatment for any reason)
Arm/Group Title Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Hide Arm/Group Description:

100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).

Placebo

Overall Number of Participants Analyzed 10 10 10
Mean (Standard Deviation)
Unit of Measure: percent
1.5  (5.20) -2.1  (12.28) 0.5  (5.91)
3.Other Pre-specified Outcome
Title Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 3
Hide Description FVC conducted before and after inhalation of the investigational product
Time Frame 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: included all subjects who received any dose of Investigational Product (included those withdrawn from treatment for any reason)
Arm/Group Title Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Hide Arm/Group Description:

100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).

Placebo

Overall Number of Participants Analyzed 10 10 10
Mean (Standard Deviation)
Unit of Measure: percent
1.2  (5.23) -2.3  (11.57) -0.9  (3.73)
Time Frame 3 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Hide Arm/Group Description

100 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

200 mg of aerosolized Alpha-1 HC inhaled daily via nebulizer for 3 weeks.

Alpha-1 HC: Alpha-1 HC is a sterile, liquid preparation of purified alpha1-proteinase inhibitor prepared from pooled human plasma.

Placebo inhaled daily via nebulizer for 3 weeks. Placebo (phosphate buffer saline with polysorbate).

Placebo

All-Cause Mortality
Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/10 (10.00%)      1/10 (10.00%)      1/10 (10.00%)    
Gastrointestinal disorders       
ABDOMINAL PAIN   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
PULMONARY EXACERBATION/   1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alpha-1 HC 100 mg Alpha-1 HC 200 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      8/10 (80.00%)      6/10 (60.00%)    
Gastrointestinal disorders       
MOUTH ULCERATION   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
VOMITING   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
ABDOMINAL PAIN UPPER   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
General disorders       
CHEST DISCOMFORT   0/10 (0.00%)  0 2/10 (20.00%)  2 1/10 (10.00%)  1
FATIGUE   1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1
CHEST PAIN   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
CHILLS   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
PAIN   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
PYREXIA   0/10 (0.00%)  0 0/10 (0.00%)  0 2/10 (20.00%)  2
Infections and infestations       
ORAL HERPES   1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1
SINUSITIS   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION   1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1
OTITIS EXTERNA   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
OTITIS MEDIA   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
Investigations       
BLOOD CREATININE INCREASED   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
BLOOD PRESSURE INCREASED   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
BREATH SOUNDS ABNORMAL   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
C-REACTIVE PROTEIN INCREASED   0/10 (0.00%)  0 2/10 (20.00%)  2 0/10 (0.00%)  0
FORCED EXPIRATORY VOLUME DECREASED   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
PHYSICAL EXAMINATION ABNORMAL   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
PULMONARY FUNCTION TEST DECREASED   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
SPUTUM ABNORMAL   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
Metabolism and nutrition disorders       
DECREASED APPETITE   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
Musculoskeletal and connective tissue disorders       
ARTHRALGIA   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
BACK PAIN   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
FLANK PAIN   0/10 (0.00%)  0 1/10 (10.00%)  1 1/10 (10.00%)  1
Nervous system disorders       
DIZZINESS   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
SINUS HEADACHE   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
Psychiatric disorders       
DEPRESSION   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
Reproductive system and breast disorders       
ENDOMETRIOSIS   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
BRONCHIAL SECRETION RETENTION   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
BRONCHOSPASM   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
COUGH   3/10 (30.00%)  3 1/10 (10.00%)  1 1/10 (10.00%)  1
DRY THROAT   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
DYSPNOEA   1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1
HAEMOPTYSIS   4/10 (40.00%)  4 1/10 (10.00%)  1 1/10 (10.00%)  1
OROPHARYNGEAL PAIN   0/10 (0.00%)  0 0/10 (0.00%)  0 2/10 (20.00%)  2
PHARYNGEAL ERYTHEMA   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
PHARYNGEAL OEDEMA   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
PULMONARY CONGESTION   1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1
PULMONARY EXACERBATION   1/10 (10.00%)  1 3/10 (30.00%)  3 0/10 (0.00%)  0
RALES   1/10 (10.00%)  1 0/10 (0.00%)  0 1/10 (10.00%)  1
RESPIRATORY TRACT IRRITATION   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
RHINITIS ALLERGIC   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
RHONCHI   0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
SPUTUM INCREASED   1/10 (10.00%)  1 1/10 (10.00%)  1 1/10 (10.00%)  1
THROAT IRRITATION   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
WHEEZING   3/10 (30.00%)  3 1/10 (10.00%)  1 0/10 (0.00%)  0
Skin and subcutaneous tissue disorders       
ALOPECIA   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
PHOTOSENSITIVITY REACTION   1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0
RASH MACULAR   0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Henry Li, PhD
Organization: Grifols Therapeutics Inc.
Phone: 919-316-6042
EMail: henry.li@grifols.com
Layout table for additonal information
Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT01684410    
Other Study ID Numbers: T6005-201
First Submitted: September 6, 2012
First Posted: September 13, 2012
Results First Submitted: August 10, 2015
Results First Posted: February 8, 2016
Last Update Posted: February 8, 2016