Inhaled treatment for lung disease caused by Alpha 1-Antitrypsin Deficiency

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

This study is testing if an inhaled treatment can help people with severe Alpha 1-Antitrypsin Deficiency slow down their lung disease.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Kamada, Ltd. (Industry-sponsored)
• Drugs / interventions: prednisone
• Locations: 9 sites (Leuven and 8 other locations)
• Trial ID: NCT04204252 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of inhaled Alpha 1-Antitrypsin (AAT) at a dose of 80 mg/day in patients with severe Alpha 1-Antitrypsin Deficiency (AATD) to determine if it can slow the progression of lung disease. Participants will receive the treatment via nebulizer, allowing direct delivery to the lungs, which is crucial for those suffering from lung conditions like emphysema or COPD. The study will measure lung function and density using spirometry and CT scans, alongside assessing quality of life and potential side effects. Over 220 participants have previously completed trials with inhaled AAT for various diseases, indicating a promising approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with a severe genetic deficiency in Alpha 1-Antitrypsin and evidence of airflow limitation.

Not a fit: Patients with mild AAT deficiency or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly slow the progression of lung disease in patients with Alpha 1-Antitrypsin Deficiency.

How similar studies have performed: Previous studies with inhaled AAT have shown positive results, suggesting this approach may be effective.

Eligibility criteria

Inclusion Criteria

1. Diagnosis of severe AAT deficiency, i.e. patients with either Pi(ZZ), Pi(Z/Null), or Pi(Null/Null) genotypes.
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 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 willing to use contraceptive methods for the duration of the study, or who are postmenopausal, or surgically sterilized.
9. Study medication use for at least 20 out of the 28 days of run-in, as recorded in the study nebulization PARI Track data.
10. Demonstrated ability to complete eDiary for at least 20 out of the first 28 days of run-in.

Exclusion Criteria

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 during the 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.

Additional eligibility criteria apply for the open label extension

Where this trial is running

Leuven and 8 other locations

• University Hospital (UZ) Leuven — Leuven, Belgium (Recruiting)
• Tays Central Hospital — Tampere, Finland (Recruiting)
• Beaumont Hospital — Dublin, Ireland (Recruiting)
• Leiden University Medical Center (LUMC) — Leiden, Za, Netherlands (Recruiting)
• Canisius Wilhelmina Hospital (CWZ) — Nijmegen, Netherlands (Recruiting)
• Skåne University Hospital — Malmö, Sweden (Recruiting)
• University Hospitals Birmingham NHS Foundation Trust — Birmingham, United Kingdom (Recruiting)
• Royal Infirmary of Edinburgh — Edinburgh, United Kingdom (Recruiting)
• University Hospital Southampton NHS Foundation Trust — Southampton, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Jan Stolk, Prof — Lumc
• Study coordinator: Sharon Gai

Conditions Alpha 1-Antitrypsin Deficiency; Alpha 1 Antitrypsin; Inhaled Alpha 1 Antitrypsin; Nebulizer