Trial Outcomes & Findings for Effect of Double Dose of Alpha 1-antitrypsin Augmentation Therapy on Lung Inflammation. (NCT NCT01669421)
NCT ID: NCT01669421
Last Updated: 2019-05-08
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)
Results posted on
2019-05-08
Participant Flow
Participant milestones
| Measure |
Studied Population
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.
|
|---|---|
|
Phase 1: Standard Dose Therapy
STARTED
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10
|
|
Phase 1: Standard Dose Therapy
COMPLETED
|
8
|
|
Phase 1: Standard Dose Therapy
NOT COMPLETED
|
2
|
|
Phase 2: Double Dose Therapy
STARTED
|
8
|
|
Phase 2: Double Dose Therapy
COMPLETED
|
8
|
|
Phase 2: Double Dose Therapy
NOT COMPLETED
|
0
|
|
Phase 3: Standard Dose Therapy
STARTED
|
8
|
|
Phase 3: Standard Dose Therapy
COMPLETED
|
8
|
|
Phase 3: Standard Dose Therapy
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Studied Population
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.
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|---|---|
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Phase 1: Standard Dose Therapy
Withdrawal by Subject
|
1
|
|
Phase 1: Standard Dose Therapy
Physician Decision
|
1
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Baseline Characteristics
Effect of Double Dose of Alpha 1-antitrypsin Augmentation Therapy on Lung Inflammation.
Baseline characteristics by cohort
| Measure |
Alpha-1 Antitrypsin (Human)
n=10 Participants
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
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
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2 Participants
n=5 Participants
|
|
Age, Continuous
|
59.6 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
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3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)Population: Subjects with AATD and COPD that require augmentation therapy
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.
Outcome measures
| Measure |
Alpha-1 Antitrypsin (Human) Standard Dose Baseline
n=8 Participants
Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4
|
Alpha-1 Antitrypsin (Human) Double Dose
n=8 Participants
Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8
|
Alpha-1 Antitrypsin (Human) Standard Dose
n=8 Participants
4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12
|
|---|---|---|---|
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Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL-2
|
14.3 pg/ml
Standard Deviation 7.3
|
8.1 pg/ml
Standard Deviation 3.1
|
10.3 pg/ml
Standard Deviation 1.7
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL-8
|
379.9 pg/ml
Standard Deviation 294.3
|
563.2 pg/ml
Standard Deviation 317.8
|
412.2 pg/ml
Standard Deviation 160.1
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL-17
|
79.0 pg/ml
Standard Deviation 27.8
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61.5 pg/ml
Standard Deviation 15.8
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67.4 pg/ml
Standard Deviation 8.5
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
BASIC FGF
|
20.7 pg/ml
Standard Deviation 9.3
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15.4 pg/ml
Standard Deviation 4.3
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16.5 pg/ml
Standard Deviation 2.1
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
GM-CSF
|
114.9 pg/ml
Standard Deviation 36.2
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89.1 pg/ml
Standard Deviation 33.6
|
105.4 pg/ml
Standard Deviation 20.8
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL-15
|
116.5 pg/ml
Standard Deviation 68.4
|
92.5 pg/ml
Standard Deviation 38.9
|
90.5 pg/ml
Standard Deviation 16.6
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL1alpha
|
30.7 pg/ml
Standard Deviation 18.7
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27.4 pg/ml
Standard Deviation 18.8
|
27.7 pg/ml
Standard Deviation 6.0
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL-18
|
9.1 pg/ml
Standard Deviation 7.4
|
8.1 pg/ml
Standard Deviation 2.0
|
7.7 pg/ml
Standard Deviation 1.6
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
M-CSF
|
43.1 pg/ml
Standard Deviation 18.9
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37.0 pg/ml
Standard Deviation 33.4
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33.1 pg/ml
Standard Deviation 19.4
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL-4
|
3.1 pg/ml
Standard Deviation 0.6
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3.0 pg/ml
Standard Deviation 0.5
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2.9 pg/ml
Standard Deviation 0.4
|
|
Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
IL-9
|
24.9 pg/ml
Standard Deviation 4.8
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23.1 pg/ml
Standard Deviation 4.1
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23.5 pg/ml
Standard Deviation 3.3
|
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Changes in Inflammatory Biomarkers in Bronchoalveolar Lavage Fluid
Eotaxin
|
154.0 pg/ml
Standard Deviation 37.7
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150.9 pg/ml
Standard Deviation 44.6
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138.0 pg/ml
Standard Deviation 16.3
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SECONDARY outcome
Timeframe: Between baseline (week 4), double dose A1PI (week 8) and again standard dose (week 12)Assess the variations in the levels of cytokines and inflammatory biomarkers using the bead technology.
Outcome measures
| Measure |
Alpha-1 Antitrypsin (Human) Standard Dose Baseline
n=8 Participants
Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4
|
Alpha-1 Antitrypsin (Human) Double Dose
n=8 Participants
Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8
|
Alpha-1 Antitrypsin (Human) Standard Dose
n=8 Participants
4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12
|
|---|---|---|---|
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Change in Inflammatory Biomarkers in Serum Samples
IL-2
|
127.3 pg/ml
Standard Deviation 114.0
|
114.5 pg/ml
Standard Deviation 81.6
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66.11 pg/ml
Standard Deviation 95.7
|
|
Change in Inflammatory Biomarkers in Serum Samples
IL-6
|
232.3 pg/ml
Standard Deviation 212.0
|
222.4 pg/ml
Standard Deviation 202.2
|
132.56 pg/ml
Standard Deviation 161.0
|
|
Change in Inflammatory Biomarkers in Serum Samples
IL-1beta
|
11.2 pg/ml
Standard Deviation 11.6
|
9.1 pg/ml
Standard Deviation 7.7
|
34.06 pg/ml
Standard Deviation 73.3
|
|
Change in Inflammatory Biomarkers in Serum Samples
IL-4
|
14.5 pg/ml
Standard Deviation 11.6
|
13.3 pg/ml
Standard Deviation 9.4
|
9.73 pg/ml
Standard Deviation 11.6
|
|
Change in Inflammatory Biomarkers in Serum Samples
IL-10
|
85.8 pg/ml
Standard Deviation 86.3
|
72.9 pg/ml
Standard Deviation 58.1
|
50.62 pg/ml
Standard Deviation 74.5
|
|
Change in Inflammatory Biomarkers in Serum Samples
IFNy
|
67.4 pg/ml
Standard Deviation 67.9
|
67 pg/ml
Standard Deviation 49.1
|
48.9 pg/ml
Standard Deviation 63.6
|
|
Change in Inflammatory Biomarkers in Serum Samples
CRP
|
476.7 pg/ml
Standard Deviation 358.9
|
1082.9 pg/ml
Standard Deviation 1971.9
|
494.5 pg/ml
Standard Deviation 453.1
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SECONDARY outcome
Timeframe: From Week 1 to week 12Outcome measures
| Measure |
Alpha-1 Antitrypsin (Human) Standard Dose Baseline
n=10 Participants
Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4
|
Alpha-1 Antitrypsin (Human) Double Dose
n=8 Participants
Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8
|
Alpha-1 Antitrypsin (Human) Standard Dose
n=8 Participants
4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12
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|---|---|---|---|
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Number of Adverse Events Reported
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0 Events
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0 Events
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0 Events
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OTHER_PRE_SPECIFIED outcome
Timeframe: Week 4 vs Week 8 vs Week 12Desmosine/isodesmosine measured using mass spectometry.
Outcome measures
| Measure |
Alpha-1 Antitrypsin (Human) Standard Dose Baseline
n=8 Participants
Alpha-1 Antitrypsin (human) 60 mg per kg per week for 4 weeks. Study week 4
|
Alpha-1 Antitrypsin (Human) Double Dose
n=8 Participants
Alpha-1 Antitrypsin (human) 120 mg/kg per week for 4 weeks. Study week 8
|
Alpha-1 Antitrypsin (Human) Standard Dose
n=8 Participants
4 weeks on A1PI at 60 mg/kg per week after the other 2 phases. Collected@ study week 12
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|---|---|---|---|
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Elastin Degradation in BAL
|
156.7 ng/ml
Standard Deviation 103.2
|
62.89 ng/ml
Standard Deviation 23.55
|
56.88 ng/ml
Standard Deviation 25.46
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Adverse Events
Phase 1: Standard Dose
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Phase 2: Double Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 3: Standard Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Phase 1: Standard Dose
n=10 participants at risk
Standard dose (60 mg/kg/week) Weeks1-4
|
Phase 2: Double Dose
n=8 participants at risk
Double dose (120 mg/kg/week) weeks 4-8
|
Phase 3: Standard Dose
n=8 participants at risk
Standard dose (60 mg/kg/week) weeks 8-12
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|---|---|---|---|
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Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
10.0%
1/10 • Number of events 1 • 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).
|
0.00%
0/8 • 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).
|
0.00%
0/8 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
10.0%
1/10 • Number of events 1 • 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).
|
0.00%
0/8 • 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).
|
0.00%
0/8 • 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).
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place