Phase III, Efficacy and Safety of "Kamada-AAT for Inhalation"

NCT04204252 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: Kamada-AAT (inhaled) 008
• Study Type: interventional
• Target: 220
• Locations: 6 countries
• Sites: 9

Brief Summary

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Keywords

Alpha 1 Antitrypsin; Inhaled Alpha 1 Antitrypsin; Nebulizer

Outcome Measures

Primary Outcomes (1)

• FEV1 post bronchodilator

  Change from baseline in post bronchodilator FEV1 at 104 weeks

  104 weeks

Secondary Outcomes (5)

• CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).

  104 weeks

• FEV1 % of predicted

  104 weeks

• FEV1/FVC %

  104 weeks

• Exacerbations

  104 weeks

• 6 minute walk test

  104 weeks

Other Outcomes (4)

• TEAEs

  130 weeks

• PiM

  130 weeks

• ADA/nADA

  130 weeks

Study Arms (2)

Inhaled AAT

ACTIVE COMPARATOR

Daily inhalation of 80 mg/day "Kamada-AAT for Inhalation" for 104 weeks

Drug: Alpha 1-Antitrypsin

Placebo

PLACEBO COMPARATOR

Daily inhalation of a solution of NaCl in phosphate buffer solution with 0.01% TWEEN-80

Drug: Placebo

Interventions

Alpha 1-Antitrypsin DRUG

Kamada's alpha 1-antitrypsin product given by inhalation using the eFlow® electronic nebulizer manufactured by PARI Pharma GmbH

Also known as: Kamada alpha 1-antitrypsin for inhalation

Inhaled AAT

Placebo DRUG

Preparation of NaCl in phosphate buffer solution with 0.01% TWEEN-80

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• % ≤ 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.

You may not qualify if:

• Immunoglobulin A (IgA) absolute deficiency defined as serum IgA levels \< 0.05 g/L.
• History of life-threatening transfusion reaction(s), allergy, anaphylactic reaction, or systemic response to human plasma-derived products.
• Two or more moderate or any severe exacerbation(s) within the year prior to baseline.
• A moderate exacerbation within 6 weeks prior to baseline.
• Use of oral or parenteral glucocorticoids in doses above 10 mg of prednisone daily or equivalent generics (substance and dose).
• 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.
• Hospitalization for any cause during the 6 weeks prior to screening.
• History of lung or liver transplant.
• On any thoracic or hepatic surgery waiting list.
• Any lung surgery within the past two years (including bronchoscopic lung volume reduction).
• Any smoking within the year prior to screening.
• 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.
• Acute or chronic hepatitis (hepatitis A, hepatitis B, hepatitis C), or positive human immunodeficiency virus (HIV) serology.
• 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.
• Signs of significant abnormalities in ECG per investigator judgment at screening.

Sponsors & Collaborators

• Kamada, Ltd.: lead
• Syneos Health: collaborator

Study Sites (9)

University Hospital (UZ) Leuven

Leuven, Belgium

RECRUITING

Tays Central Hospital

Tampere, Finland

RECRUITING

Beaumont Hospital

Dublin, D09 YD60, Ireland

RECRUITING

Leiden University Medical Center (LUMC)

Leiden, ZA, 2333ZA, Netherlands

RECRUITING

Canisius Wilhelmina Hospital (CWZ)

Nijmegen, 6532SZ, Netherlands

RECRUITING

Skåne University Hospital

Malmo, SE-20502, Sweden

RECRUITING

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2GW, United Kingdom

RECRUITING

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

RECRUITING

Related Publications (1)

• Kappe NN, Alagem N, Tov N, Stolk J. Governmental Non-Pharmaceutical Interventions during the COVID-19 Pandemic and the COPD Exacerbation and Respiratory Infection Rate in Patients with Alpha-1 Antitrypsin Deficiency. COPD. 2023 Dec;20(1):292-297. doi: 10.1080/15412555.2023.2249108.

  PMID: 37665565 DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Interventions

alpha 1-Antitrypsin; Inhalation

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Jan Stolk, Prof

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sharon Gai

CONTACT

972 8 9406472; eligibility@innovaate-study.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study participants will be randomized for 2 years of double-blind treatment with AAT for Inhalation 80 mg/d or placebo, followed by an additional 2 years of open label treatment with AAT for inhalation 80 mg/L. Participants will be followed up for safety for 24 weeks following the end of study treatment.

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 18, 2019
• Study Start: November 25, 2019
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: September 4, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); BE (1); IE (1); FI (1); NL (2); SE (1)