Trial Outcomes & Findings for Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation" (NCT NCT02001688)
NCT ID: NCT02001688
Last Updated: 2020-01-18
Results Overview
Patients underwent bronchoalveolar lavage (BAL) prior to initiation of drug and then again after 3 months. Concentration of AAT in the BAL was measured by an enzyme linked immunosorbent assay (ELISA) specific for the normal form of AAT (piM). Urea was also measured in order to determine the dilution factor of the BAL fluid and calculate the concentration of AAT in the ELF.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
12 weeks from initiation of study drug
Results posted on
2020-01-18
Participant Flow
There were 2 clinical sites. At each site, 18 subjects were recruited and randomized 2:1 to receive either "Kamada-AAT for Inhalation" 80 mg/day (site 1) or 160 mg/day (site 2) or placebo. This gave a total of 12 patients randomized to receive 80 mg/day active drug, 12 patients randomized to receive 160 mg/day active drug, and 12 patients placebo
There were no pre-assignment changes
Participant milestones
| Measure |
Kamada-AAT for Inhalation, 80mg
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
Placebo inhaled daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
12
|
|
Overall Study
COMPLETED
|
12
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
Kamada-AAT for Inhalation, 80mg
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
Placebo inhaled daily
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation"
Baseline characteristics by cohort
| Measure |
Kamada-AAT for Inhalation, 80mg
n=12 Participants
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
n=12 Participants
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
n=12 Participants
Placebo inhaled daily
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 8.69 • n=5 Participants
|
55.3 years
STANDARD_DEVIATION 10.13 • n=7 Participants
|
56.3 years
STANDARD_DEVIATION 4.77 • n=5 Participants
|
55.7 years
STANDARD_DEVIATION 7.96 • n=4 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White Non-Hispanic
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
12 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
BMI
|
30.0 kg/m^2
STANDARD_DEVIATION 4.3 • n=5 Participants
|
28.3 kg/m^2
STANDARD_DEVIATION 8.3 • n=7 Participants
|
25.8 kg/m^2
STANDARD_DEVIATION 4.5 • n=5 Participants
|
28.0 kg/m^2
STANDARD_DEVIATION 6.1 • n=4 Participants
|
|
%Predicted forced expiratory volume in one second (FEV1)
|
81.7 %
STANDARD_DEVIATION 17.9 • n=5 Participants
|
73.2 %
STANDARD_DEVIATION 20.1 • n=7 Participants
|
78.1 %
STANDARD_DEVIATION 20.0 • n=5 Participants
|
77.6 %
STANDARD_DEVIATION 19.1 • n=4 Participants
|
PRIMARY outcome
Timeframe: 12 weeks from initiation of study drugPopulation: Intention to treat (ITT) population with values available in BAL at baseline and 12 weeks
Patients underwent bronchoalveolar lavage (BAL) prior to initiation of drug and then again after 3 months. Concentration of AAT in the BAL was measured by an enzyme linked immunosorbent assay (ELISA) specific for the normal form of AAT (piM). Urea was also measured in order to determine the dilution factor of the BAL fluid and calculate the concentration of AAT in the ELF.
Outcome measures
| Measure |
Kamada-AAT for Inhalation, 80mg
n=12 Participants
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
n=10 Participants
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
n=10 Participants
Combined placebo results from patients at the two clinical sites
|
|---|---|---|---|
|
Change From Baseline in the Concentration of Antigenic Alpha-1 Antitrypsin (AAT) in the Lung Epithelial Lining Fluid (ELF)
|
4551.023 nmol
Interval 2587.0 to 6835.6
|
13454.772 nmol
Interval 1020.7 to 70907.95
|
-27.15 nmol
Interval -103.6 to 196.7
|
PRIMARY outcome
Timeframe: 12 weeks from initiation of study drugITT population with baseline and 12 week values. Patients underwent bronchoalveolar lavage (BAL) prior to initiation of drug and then again after 3 months. Concentration of AAT in the BAL was measured by an antineutrophil elastase capacity (ANEC) assay. Urea was also measured in order to determine the dilution factor of the BAL fluid and calculate the concentration of AAT in the ELF.
Outcome measures
| Measure |
Kamada-AAT for Inhalation, 80mg
n=12 Participants
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
n=10 Participants
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
n=10 Participants
Combined placebo results from patients at the two clinical sites
|
|---|---|---|---|
|
Change From Baseline to 12 Weeks in the Concentration of Functional AAT (Alpha-1 Antitrypsin) in ELF
|
2766.343 nmol
Interval 840.9 to 3800.3
|
3557.563 nmol
Interval 1582.8 to 10673.2
|
5.831 nmol
Interval -1032.0 to 884.3
|
SECONDARY outcome
Timeframe: 12 weeks from initiation of study drugIntention to treat (ITT) population with baseline and 12 week values.The median change from baseline to Week 12 in the levels of M-specific AAT (piM) in plasma was measured using a specific ELISA assay for M-specific AAT (piM)
Outcome measures
| Measure |
Kamada-AAT for Inhalation, 80mg
n=11 Participants
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
n=11 Participants
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
n=11 Participants
Combined placebo results from patients at the two clinical sites
|
|---|---|---|---|
|
Change From Baseline in Levels of M Specific AAT in Plasma (PiM)
|
113.17 nM
Interval 56.3 to 158.1
|
90.73 nM
Interval 37.3 to 369.7
|
-4.02 nM
Interval -9.8 to 4.9
|
SECONDARY outcome
Timeframe: 12 weeks from initiation of study drugPatients underwent a BAL procedure at baseline and 12 weeks and the fluid was analyzed to calculate the change from baseline in the concentration of complexes between AAT and neutrophil elastase in the ELF
Outcome measures
| Measure |
Kamada-AAT for Inhalation, 80mg
n=12 Participants
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
n=10 Participants
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
n=10 Participants
Combined placebo results from patients at the two clinical sites
|
|---|---|---|---|
|
Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF
|
38.71 nM
Interval 8.4 to 66.8
|
46.225 nM
Interval 17.6 to 436.3
|
0 nM
Interval -2.0 to 1.3
|
Adverse Events
Kamada-AAT for Inhalation, 80mg
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Kamada-AAT for Inhalation, 160mg
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Kamada-AAT for Inhalation, 80mg
n=12 participants at risk
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
n=12 participants at risk
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
n=12 participants at risk
Placebo inhaled daily
|
|---|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
Other adverse events
| Measure |
Kamada-AAT for Inhalation, 80mg
n=12 participants at risk
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
Kamada-AAT for Inhalation, 160mg
n=12 participants at risk
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
Placebo
n=12 participants at risk
Placebo inhaled daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/12 • 12 weeks
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Gastrointestinal disorders
Lip swelling
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
General disorders
Chest pain
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
General disorders
Chills
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
General disorders
Feeling jittery
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
General disorders
Pyrexia
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Infections and infestations
Bronchitis
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Infections and infestations
Ear infection
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Infections and infestations
Folliculitis
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Infections and infestations
Hordeolum
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Infections and infestations
Influenza
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
16.7%
2/12 • Number of events 3 • 12 weeks
|
|
Infections and infestations
Pneumonia
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Infections and infestations
Sinusitis
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Infections and infestations
Urinary tract infection
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Infections and infestations
Viral respiratory tract infection
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Investigations
Blood cholesterol increased
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Investigations
Blood glucose increased
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Investigations
Electrocardiogram abnormal
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Investigations
Platelet count decreased
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Investigations
Pulmonary function test decreased
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Investigations
Urine analysis
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Nervous system disorders
Headache
|
16.7%
2/12 • Number of events 3 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Nervous system disorders
Sinus headache
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Nervous system disorders
Somnolence
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Renal and urinary disorders
Haematuria
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Renal and urinary disorders
Proteinuria
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/12 • 12 weeks
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
4/12 • Number of events 5 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
25.0%
3/12 • Number of events 4 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discharge discolouration
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
16.7%
2/12 • Number of events 2 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
|
Vascular disorders
Hypertension
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
8.3%
1/12 • Number of events 1 • 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place