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

Participant Flow

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
Arm/Group Description	100 mg of aerosolized Alpha-1 HC in...	200 mg of aerosolized Alpha-1 HC in...	Placebo inhaled daily via nebulizer...
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

Baseline Characteristics

Arm/Group Title		Alpha-1 HC 100 mg	Alpha-1 HC 200 mg	Placebo	Total
Arm/Group Description		100 mg of aerosolized Alpha-1 HC in...	200 mg of aerosolized Alpha-1 HC in...	Placebo inhaled daily via nebulizer...	Total of all reporting groups
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
Baseline Analysis Population Description		...
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
United States		10	10	10	30

Outcome Measures

1.Primary Outcome


Title	Adverse Events
Description	adverse event frequency
Description	adverse event frequency
Time Frame	3 weeks

Outcome Measure Data

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
Arm/Group Description:	100 mg of aerosolized Alpha-1 HC in...	200 mg of aerosolized Alpha-1 HC in...	Placebo inhaled daily via nebulizer...
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
Description	FEV1 conducted before and after inhalation of the investigational prod...
Description	FEV1 conducted before and after inhalation of the investigational product at study visits.
Time Frame	3 weeks

Outcome Measure Data

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
Arm/Group Description:	100 mg of aerosolized Alpha-1 HC in...	200 mg of aerosolized Alpha-1 HC in...	Placebo inhaled daily via nebulizer...
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
Description	FVC conducted before and after inhalation of the investigational produ...
Description	FVC conducted before and after inhalation of the investigational product
Time Frame	3 weeks

Outcome Measure Data

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
Arm/Group Description:	100 mg of aerosolized Alpha-1 HC in...	200 mg of aerosolized Alpha-1 HC in...	Placebo inhaled daily via nebulizer...
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)

Adverse Events

Time Frame	3 weeks
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Alpha-1 HC 100 mg		Alpha-1 HC 200 mg		Placebo
Arm/Group Description	100 mg of aerosolized Alpha-1 HC in...		200 mg of aerosolized Alpha-1 HC in...		Placebo inhaled daily via nebulizer...
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	--/--		--/--		--/--
Serious Adverse Events 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
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

Limitations and Caveats

[Not Specified]

More Information

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

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