Prospective Phase 3 Multi-center 2-Year Placebo Controlled Double Blind Study to Evaluate the Efficacy and Safety of Kamada-AAT for Inhalation 80 mg/Day in Alpha-1 Antitrypsin Deficiency With Moderate and Severe Airflow Limitation Followed by a 2-Year Open Label Extension
The goal of this clinical trial is to learn if AAT for inhalation, at a dose of 80 mg/day can slow the progression of lung disease in people who have lung disease caused by severe genetic deficiency in Alpha 1 Antitrypsin (AATD). The main question it aims to answer is: • Can daily treatment with Kamada AAT for inhalation at a dose of 80 mg/day prevent or slow lung function worsening ? Lung function will be measured by spirometry. Other questions it aims to answer are: * Can daily treatment with Kamada AAT for inhalation at a dose of 80 mg/day prevent or slow lung density loss ? Lung density will be measured by a CT scan. * Can daily treatment with Kamada AAT for inhalation at a dose of 80 mg/day prevent or slow lung disease from worsening ? Lung disease will be measured using spirometry, lung volume, gas diffusion, six minute walk test, quality of life questionaires and biomarkers. * What medical problems do participants have when taking AAT for inhalation 80 mg/day daily ? Researchers will compare AAT for inhalation to a placebo (a look-alike substance that contains no drug) to see if AAT for inhalation works to treat AAT-deficiency related lung disease. Study participants will receive either AAT for inhalation or placebo for the first two years of the study. During the third and fourth years of the study all participants will receive AAT for inhalation regardless of which drug they received during the first two years. Participants will: * Inhale the study drug every day * Clean and disinfect the nebulizer every day * Document daily symptoms and study drug use in an electronic diary * Visit the clinic for tests and assessments. There are 11 clinic visits during the first two years of the study and 5-6 clinic visits during the third and fourth year, combined. After treatment ends, participants will visit the clinic 3 times in half a year.
• Diagnosis of severe AAT deficiency, i.e. patients with either Pi(ZZ), Pi(Z/Null), or Pi(Null/Null) genotypes.
• Serum AAT levels ≤ 11 µM at screening.
• Lung disease with clinical evidence of airflow limitation (post bronchodilator FEV1/SVC≤70%) at screening.
• 40% ≤ FEV1 ≤ 80% of predicted post-bronchodilator at screening.
• Patients who are either naïve or washed out of any AAT treatment for at least 8 weeks prior to randomization.
• Age between 18 to 65 years inclusive at screening.
• Able to read and sign informed consent and willing to participate in the study.
• Males or non-pregnant, non-lactating females whose screening pregnancy test is negative, who are willing to use contraceptive methods for the duration of the study, or who are postmenopausal, or surgically sterilized.
• Study medication use for at least 20 out of the 28 days of run-in, as recorded in the study nebulization PARI Track data.
⁃ Demonstrated ability to complete eDiary for at least 20 out of the first 28 days of run-in.