Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
To evaluate different doses of "Kamada-AAT for Inhalation" on the levels of alpha 1-proteinase inhibitor and other analytes in epithelial lining fluid (ELF) and serum and to assess the safety of the treatment in subjects with AAT Deficiency.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kamada-AAT for Inhalation, 80mg | Experimental | Daily inhalation of Kamada-AAT for Inhalation, 80mg |
|
| Placebo | Placebo Comparator | Placebo administered by inhalation daily |
|
| Kamada-AAT for Inhalation, 160mg | Experimental | Daily inhalation of Kamada-AAT for Inhalation, 160mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kamada-AAT for Inhalation, 80mg | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Concentration of Antigenic Alpha-1 Antitrypsin (AAT) in the Lung Epithelial Lining Fluid (ELF) | 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. | 12 weeks from initiation of study drug |
| Change From Baseline to 12 Weeks in the Concentration of Functional AAT (Alpha-1 Antitrypsin) in ELF | ITT 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. | 12 weeks from initiation of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Levels of M Specific AAT in Plasma (PiM) | Intention 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) | 12 weeks from initiation of study drug |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida, Pulmonary, Critical Care & Sleep Medicine | Gainesville | Florida | 32610 | United States | ||
There were no pre-assignment changes
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
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Kamada-AAT for Inhalation, 80mg | Daily inhalation of Kamada-AAT for Inhalation, 80mg |
| FG001 | Kamada-AAT for Inhalation, 160mg | Daily inhalation of Kamada-AAT for Inhalation, 160mg |
| FG002 | Placebo | Placebo inhaled daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
ITT population
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Kamada-AAT for Inhalation, 80mg | Daily inhalation of Kamada-AAT for Inhalation, 80mg |
| BG001 | Kamada-AAT for Inhalation, 160mg | Daily inhalation of Kamada-AAT for Inhalation, 160mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in the Concentration of Antigenic Alpha-1 Antitrypsin (AAT) in the Lung Epithelial Lining Fluid (ELF) | 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. | Intention to treat (ITT) population with values available in BAL at baseline and 12 weeks | Posted | Median | 95% Confidence Interval | nmol | 12 weeks from initiation of study drug |
|
12 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Kamada-AAT for Inhalation, 80mg | Daily inhalation of Kamada-AAT for Inhalation, 80mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment | Community acquired pneumonia |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head of Clinical Operations | Kamada Ltd | +972-72-2219172 | sharonc@kamada.com |
Not provided
| ID | Term |
|---|---|
| D019896 | alpha 1-Antitrypsin Deficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001239 | Inhalation |
| ID | Term |
|---|---|
| D015656 | Respiratory Mechanics |
| D012119 | Respiration |
| D012143 | Respiratory Physiological Phenomena |
| D002943 | Circulatory and Respiratory Physiological Phenomena |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
| Kamada-AAT for Inhalation, 160mg | Drug |
|
| Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF |
Patients 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 |
| 12 weeks from initiation of study drug |
| The University of Texas Health Science Center at Tyler Center for Clinical Research |
| Tyler |
| Texas |
| 75708 |
| United States |
| BG002 | Placebo | Placebo inhaled daily |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| %Predicted forced expiratory volume in one second (FEV1) | Mean | Standard Deviation | % |
|
| Kamada-AAT for Inhalation, 160mg |
Daily inhalation of Kamada-AAT for Inhalation, 160mg |
| OG002 | Placebo | Combined placebo results from patients at the two clinical sites |
|
|
|
| Primary | Change From Baseline to 12 Weeks in the Concentration of Functional AAT (Alpha-1 Antitrypsin) in ELF | ITT 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. | Posted | Median | 95% Confidence Interval | nmol | 12 weeks from initiation of study drug |
|
|
|
|
| Secondary | Change From Baseline in Levels of M Specific AAT in Plasma (PiM) | Intention 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) | Posted | Median | 95% Confidence Interval | nM | 12 weeks from initiation of study drug |
|
|
|
|
| Secondary | Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF | Patients 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 | Posted | Median | 95% Confidence Interval | nM | 12 weeks from initiation of study drug |
|
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 10 |
| 12 |
| EG001 | Kamada-AAT for Inhalation, 160mg | Daily inhalation of Kamada-AAT for Inhalation, 160mg | 0 | 12 | 1 | 12 | 8 | 12 |
| EG002 | Placebo | Placebo inhaled daily | 0 | 12 | 0 | 12 | 7 | 12 |
|
| Lip swelling | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Feeling jittery | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Viral respiratory tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Electrocardiogram abnormal | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Pulmonary function test decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Urine analysis | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nasal discharge discolouration | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pruritis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
Not provided
Not provided
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013352 | Subcutaneous Emphysema |
| D004646 | Emphysema |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
One-sided test was used for antigenic and functional AAT levels to maintain overall 2.5% level of significance |
| 0.0193 |
| Superiority |
| Wilcoxon (Mann-Whitney) | One-sided test was used for antigenic and functional AAT levels to maintain overall 2.5% level of significance | 0.2485 | Superiority |