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Trial record 3 of 10 for:    Alpha-1-proteinase inhibitor AND ELANE

Effect of Double Dose of Alpha 1-antitrypsin Augmentation Therapy on Lung Inflammation.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01669421
Recruitment Status : Completed
First Posted : August 21, 2012
Results First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Collaborator:
CSL Behring
Information provided by (Responsible Party):
Michael Campos, MD, University of Miami

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Alpha 1 Antitrypsin Deficiency
Intervention Drug: Alpha-1 Antitrypsin (human)
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Studied Population
Hide Arm/Group Description All patients belong to one study arm. First they received standard dose augmentation therapy (60 mg/kg/week) x 4 weeks, then they receive experimental double dose (120 mg/kg/week) x 4 weeks and finally return to standard dose (60 mg/kg/week) for 4 additional weeks.
Period Title: Phase 1: Standard Dose Therapy
Started 10
Completed 8
Not Completed 2
Reason Not Completed
Withdrawal by Subject             1
Physician Decision             1
Period Title: Phase 2: Double Dose Therapy
Started 8
Completed 8
Not Completed 0
Period Title: Phase 3: Standard Dose Therapy
Started 8
Completed 8
Not Completed 0
Arm/Group Title Alpha-1 Antitrypsin (Human)
Hide Arm/Group Description

Alpha-1 Antitrypsin (human) 120 mg per kg per week for 4 weeks

Alpha-1 Antitrypsin (human): Comparison of Zemaira (Alpha 1 Antitrypsin Human) 120 mg/kg/weekly for four weeks versus 2 phases with same drug administered at standard doses of 60 mg/kg/weekly for four weeks each

Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
<=18 years
0
   0.0%
Between 18 and 65 years
8
  80.0%
>=65 years
2
  20.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
59.6  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
3
  30.0%
Male
7
  70.0%
1.Primary Outcome
Title Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
Hide Description

Assess the variations in the levels of several cytokines and inflammatory biomarkers in BAL after changing A1PI dosing.

Measures were done using the bead technology.

Time Frame Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with AATD and COPD that require augmentation therapy
Arm/Group Title Alpha-1 Antitrypsin (Human) Standard Dose Baseline Alpha-1 Antitrypsin (Human) Double Dose Alpha-1 Antitrypsin (Human) Standard Dose
Hide Arm/Group Description:
Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4
Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8
4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12
Overall Number of Participants Analyzed 8 8 8
Mean (Standard Deviation)
Unit of Measure: pg/ml
IL-2 14.3  (7.3) 8.1  (3.1) 10.3  (1.7)
IL-8 379.9  (294.3) 563.2  (317.8) 412.2  (160.1)
IL-17 79.0  (27.8) 61.5  (15.8) 67.4  (8.5)
BASIC FGF 20.7  (9.3) 15.4  (4.3) 16.5  (2.1)
GM-CSF 114.9  (36.2) 89.1  (33.6) 105.4  (20.8)
IL-15 116.5  (68.4) 92.5  (38.9) 90.5  (16.6)
IL1alpha 30.7  (18.7) 27.4  (18.8) 27.7  (6.0)
IL-18 9.1  (7.4) 8.1  (2.0) 7.7  (1.6)
M-CSF 43.1  (18.9) 37.0  (33.4) 33.1  (19.4)
IL-4 3.1  (0.6) 3.0  (0.5) 2.9  (0.4)
IL-9 24.9  (4.8) 23.1  (4.1) 23.5  (3.3)
Eotaxin 154.0  (37.7) 150.9  (44.6) 138.0  (16.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose
Comments IL-2
Type of Statistical Test Other
Comments Data was analyzed with multiple repeat ANOVA for all visits and paired samples were also evaluated.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments IL-4
Type of Statistical Test Other
Comments Kruskal-Wallis
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments IL-8
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments IL-9
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments IL-17
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments FGF
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments Eotaxin
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments GM-CSF
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments IL15
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments IL-1a
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.90
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments IL18
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments M-CSF
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
2.Secondary Outcome
Title Change in Inflammatory Biomarkers in Serum Samples
Hide Description Assess the variations in the levels of cytokines and inflammatory biomarkers using the bead technology.
Time Frame Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alpha-1 Antitrypsin (Human) Standard Dose Baseline Alpha-1 Antitrypsin (Human) Double Dose Alpha-1 Antitrypsin (Human) Standard Dose
Hide Arm/Group Description:
Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks
A1PI at 120 mg/kg per week for 4 weeks after subjects received 4 weeks standard dose
4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12
Overall Number of Participants Analyzed 8 8 8
Mean (Standard Deviation)
Unit of Measure: pg/ml
IL-2 127.3  (114.0) 114.5  (81.6) 66.11  (95.7)
IL-6 232.3  (212.0) 222.4  (202.2) 132.56  (161.0)
IL-1beta 11.2  (11.6) 9.1  (7.7) 34.06  (73.3)
IL-4 14.5  (11.6) 13.3  (9.4) 9.73  (11.6)
IL-10 85.8  (86.3) 72.9  (58.1) 50.62  (74.5)
IFNy 67.4  (67.9) 67  (49.1) 48.9  (63.6)
CRP 476.7  (358.9) 1082.9  (1971.9) 494.5  (453.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments No power calculation and this is an exploratory pilot analysis We expected cytokines to decrease after subjects receive double dose and a rebound after administering standard dose.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
3.Secondary Outcome
Title Number of Adverse Events Reported
Hide Description [Not Specified]
Time Frame From Week 1 to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alpha-1 Antitrypsin (Human) Standard Dose Baseline Alpha-1 Antitrypsin (Human) Double Dose Alpha-1 Antitrypsin (Human) Standard Dose
Hide Arm/Group Description:
Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks
A1PI at 120 mg/kg per week for 4 weeks after subjects received 4 weeks standard dose
60 mg/kg per week after the prior 2 phases
Overall Number of Participants Analyzed 10 8 8
Measure Type: Number
Unit of Measure: Events
0 0 0
4.Other Pre-specified Outcome
Title Elastin Degradation in BAL
Hide Description Desmosine/isodesmosine measured using mass spectometry.
Time Frame Week 4 vs Week 8 vs Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alpha-1 Antitrypsin (Human) Standard Dose Baseline Alpha-1 Antitrypsin (Human) Double Dose Alpha-1 Antitrypsin (Human) Standard Dose
Hide Arm/Group Description:
Alpha-1 Antitrypsin (human) 60 mg/kg per week for 4 weeks (measure at week 4)
A1PI at 120 mg/kg per week x 4 weeks (measure at week 8)
A1PI at 60 mg/kg per week after double dose (measured at week 12)
Overall Number of Participants Analyzed 8 8 8
Mean (Standard Deviation)
Unit of Measure: ng/ml
156.7  (103.2) 62.89  (23.55) 56.88  (25.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments Desmosine (DES) and isodesmosine (IDES) are used as indicator of elastin degradation. Levels of DES/IDES were measured using high-performance liquid chromatography and tandem mass spectrometry.
Type of Statistical Test Other
Comments between Week 4 and Week 8
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Double Dose, Alpha-1 Antitrypsin (Human) Standard Dose
Comments between Week 8 and Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Alpha-1 Antitrypsin (Human) Standard Dose Baseline, Alpha-1 Antitrypsin (Human) Standard Dose
Comments between Week 4 and Week 12
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Time Frame Adverse event was recorded for each subject from study enrollment (day 0) through study end which was on the day of the last bronchoscopy at the end of phase 3 (week 12). Each subject was assessed weekly by phone calls and in-person at the end of each phase (day of bronchoscopies).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1: Standard Dose Phase 2: Double Dose Phase 3: Standard Dose
Hide Arm/Group Description Standard dose (60 mg/kg/week) Weeks1-4 Double dose (120 mg/kg/week) weeks 4-8 Standard dose (60 mg/kg/week) weeks 8-12
All-Cause Mortality
Phase 1: Standard Dose Phase 2: Double Dose Phase 3: Standard Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/8 (0.00%)      0/8 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1: Standard Dose Phase 2: Double Dose Phase 3: Standard Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/8 (0.00%)      0/8 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1: Standard Dose Phase 2: Double Dose Phase 3: Standard Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/10 (20.00%)      0/8 (0.00%)      0/8 (0.00%)    
Respiratory, thoracic and mediastinal disorders       
Hemoptysis * [1]  1/10 (10.00%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
Respiratory distress * [2]  1/10 (10.00%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
1 patient developed mild hemoptysis after bronchoscopy # 1 and withdrew from study
[2]
1 patient developed respiratory distress after bronchoscopy # 1 and PI withdrew pt from study
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Michael Campos
Organization: University of Miami
Phone: 305-243-3045
EMail: mcampos1@med.miami.edu
Layout table for additonal information
Responsible Party: Michael Campos, MD, University of Miami
ClinicalTrials.gov Identifier: NCT01669421     History of Changes
Other Study ID Numbers: 20100844
First Submitted: August 14, 2012
First Posted: August 21, 2012
Results First Submitted: August 23, 2017
Results First Posted: May 8, 2019
Last Update Posted: May 8, 2019