AATD congenital lung disease
Conditions
Interventions
Active Product: Alpha-1 Proteinase Inhibitor (Alpha-1 Antitrypsin) (human A1PI)
Dosage form: Nebulizer solution 2% AAT
Dosage frequency: Once daily preferably in the afternoon/evening
Mode of Adminis
Sponsors
Kamada Ltd.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Double-Blind Period 1. Diagnosis of severe AAT deficiency, i.e. patients with either Pi(ZZ), Pi(Z/Null), or Pi(Null/Null) genotypes confirmed by genotype blood test documented prior to screening. 2. Serum AAT levels
Exclusion criteria
Exclusion criteria: Double-Blind Period 1. Immunoglobulin A (IgA) absolute deficiency defined as serum IgA levels< 0.05 g/L. 2. History of life-threatening transfusion reaction(s), allergy, anaphylactic reaction, or systemic response to human plasma-derived products. 3. Two or more moderate or any severe exacerbation(s) within the year prior to baseline. 4. A moderate exacerbation within 6 weeks prior to baseline. 5. Use of oral or parenteral glucocorticoids in doses above 10 mg of prednisone daily or equivalent generics (substance and dose). 6. Clinically significant inter-current illnesses (except for respiratory or liver disease secondary to AAT deficiency), including cardiac, hepatic, renal, endocrine, neurological, hematological, neoplastic, immunological, skeletal, or other. Patients might be included after consultation with the treating physician and the sponsor if, in the opinion of the Investigator, their condition will not interfere with the safety, compliance or other aspects of this study. 7. Hospitalization for any cause 6 weeks prior to screening. 8. History of lung or liver transplant. 9. On any thoracic or hepatic surgery waiting list. 10. Any lung surgery within the past two years (including bronchoscopic lung volume reduction). 11. Any smoking within the year prior to screening. 12. Evidence of alcohol abuse or history of alcohol abuse, or use of illegal drugs and/or abuse of legally prescribed drugs in the last 5 years prior to screening. 13. Acute or chronic hepatitis (hepatitis A, hepatitis B, hepatitis C), or positive human immunodeficiency virus (HIV) serology. 14. Signs of significant abnormalities in serum hematology, serum chemistry, serum inflammatory / immunogenic markers and urinalysis per investigator judgment, taking into considerations the potential effects of the AAT deficiency. 15. Signs of significant abnormalities in ECG per investigator judgment at screening. 16. Presence of psychiatric/ mental disorder or any other medical disorder that might impair the patient*s ability to give informed consent or to comply with the requirements of the study protocol. If, in the opinion of the Investigator, the condition will not interfere with the compliance or other aspects of this study, the patient might be included after consultation with the treating physician and the sponsor. 17. Participation in another clinical trial involving investigational medication or interventional treatment within 30 days and/or last dose 5 half-lives prior to screening visit. 18. Inability to attend scheduled clinic visits and/or comply with study protocol. 19. Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol. Open-Label Period 1. Any adverse event(s) in the DB period and/or medical condition that, in the opinion of the investigator, might prevent the patient from safely participating in the OLE period of the study, including but not limited to: a. Occurrence of a life-threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products. b. Received lung transplant, entered a waiting list for lung transplantation, or underwent lung surgery. The investigator should consult the sponsor before inclusion of any patient with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DB period FEV1 (L) post bronchodilator change from baseline at 104 weeks. OLE period 1. FEV1 (L) post bronchodilator change from DB baseline at OLE 104 weeks (total 208 weeks), and from OLE baseline at OLE 104 weeks (total 104 weeks of open label treatment), stratified by treatment during the DB part. 2. Change from DB at OLE 104 weeks (total 208 weeks of treatment), and from OLE baseline at OLE 104 weeks (total 104 weeks), in CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC), stratified by treatment during the DB part. 3. Change from OLE baseline over 104 weeks of open-label treatment in Post bronchodilator FEV1 % of predicted, FEV1/FVC %, as well as in postbronchodilator volumes (body plethysmography) and diffusion (DLCO), stratified by treatment during the DB part. 4. BODE index score and 6MWT and MMRC dyspnea score from OLE baseline over 104 weeks of open-label treatment stratified by treatment during the DB part. 5. Quality of life score as measured by the COPD assessment tool (CAT) and EQ-5D-5L from OLE baseline over 104 weeks of open-label treatment, stratified by treatment during the DB part. 6. Desmosine level in plasma from OLE baseline over 104 weeks of open label treatment, stratified by treatment during the DB part. | — |
Secondary
| Measure | Time frame |
|---|---|
| DB period 1. Change from baseline over 104 weeks of treatment in CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC). 2. Change from baseline over 104 weeks of treatment in Post bronchodilator spirometry measures a. FEV1 % of predicted b. FEV1/FVC% 3. Exacerbations; annual rate by severity, and duration. 4. Change from baseline over 104 weeks of treatment in 6-minute walk test (6MWT). | — |
Countries
Netherlands
Outcome results
None listed