Adult Patients with Congenital Alpha-1 Antitrypsin Deficiency with Moderate and Severe Airflow Limitation (40% = FEV1 = 80% of predicted
Conditions
Sponsors
Kamada Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 = 11 µM at screening. 3. Lung disease with clinical evidence of airflow limitation (post bronchodilator FEV1/SVC=70%) at screening. 4. 40% = FEV1 = 80% of predicted post-bronchodilator at screening. 5. Patients who are either naïve or washed out of any AAT treatment (by IV) for at least 8 weeks prior to randomization. 6. Age between 18 to 65 years inclusive at screening. 7. Able to read and sign informed consent and willing to participate in the study. 8. Males or non-pregnant, non-lactating females whose screening pregnancy test is negative, who are using contraceptive methods deemed reliable by the investigator, who are post-menopausal, or are surgically sterilized. 9. High compliance during run in defined as study medication use and e-Diary compliance for at least 20 out of the 28 days of run in. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 220 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Immunoglobulin A (IgA) absolute deficiency defined as serum IgA levels<0.05 g/L at screening. 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 the baseline visit. 4. A moderate exacerbation within 6 weeks prior to the 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. Previous exposure to inhaled AAT. 18. 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. 19. Inability to attend scheduled clinic visits and/or comply with study protocol. 20. Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective To assess the efficacy of Kamada-AAT for Inhalation administered at a dose of 80 mg daily vs. placebo, with efficacy measured by FEV1 post bronchodilator change from baseline at 104 weeks ;Secondary Objective: Secondary Objectives To assess the efficacy of Kamada-AAT for Inhalation administered at a dose of 80 mg daily vs placebo as measured by computed tomography (CT) densitometry change from baseline at 104 weeks. Safety Objective 1. To assess the safety of Kamada-AAT for Inhalation administered at a dose of 80 mg daily vs placebo 2. To assess the immunogenicity of Kamada-AAT for Inhalation and characterize the effect of Anti-drug antibodies (ADA) on drug levels in plasma. First (Safety) Cohort Objective To assess the safety of Kamada-AAT for Inhalation administered at a dose of 80 mg vs placebo once daily during the first 24 weeks of treatment.;Primary end point(s): FEV1 (L) post bronchodilator change from baseline at 104 weeks.;Timepoint(s) of evaluation of this end point: at 104 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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).;Timepoint(s) of evaluation of this end point: at 104 weeks | — |
Countries
Belgium, Finland, Ireland, Netherlands, Sweden, United Kingdom
Contacts
Public ContactSharon Castro
Kamada Ltd.
Outcome results
None listed