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

NCT ID: NCT04204252

Last Updated: 2025-09-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-25

Study Completion Date

2031-06-30

Brief Summary

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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.

Detailed Description

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Individuals with a genetic deficiency of alpha-1-antitrypsin (AATD) are at a significantly increased risk (80-100%) of developing lung disease (emphysema or COPD). This study is designed to administer a solution of AAT by nebulizer so that patients can inhale the drug instead of requiring infusions as in current treatment. A significant advantage of inhalation is that the AAT is directly transferred to the lungs, which is the site most in need of the protein. Previous results show that in addition to the added convenience, treatment restores normal levels of active AAT to the lung. To date, more than 220 participants have completed clinical trials with AAT for inhalation for several diseases.

Conditions

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Alpha 1-Antitrypsin Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Inhaled AAT

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

Group Type ACTIVE_COMPARATOR

Alpha 1-Antitrypsin

Intervention Type DRUG

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Alpha 1-Antitrypsin

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Kamada alpha 1-antitrypsin for inhalation

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Syneos Health

OTHER

Sponsor Role collaborator

Kamada, Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jan Stolk, Prof

Role: PRINCIPAL_INVESTIGATOR

LUMC

Locations

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University Hospital (UZ) Leuven

Leuven, , Belgium

Site Status RECRUITING

Tays Central Hospital

Tampere, , Finland

Site Status RECRUITING

Beaumont Hospital

Dublin, , Ireland

Site Status RECRUITING

Leiden University Medical Center (LUMC)

Leiden, ZA, Netherlands

Site Status RECRUITING

Canisius Wilhelmina Hospital (CWZ)

Nijmegen, , Netherlands

Site Status RECRUITING

Skåne University Hospital

Malmo, , Sweden

Site Status RECRUITING

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status RECRUITING

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Site Status RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status RECRUITING

Countries

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Belgium Finland Ireland Netherlands Sweden United Kingdom

Central Contacts

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Sharon Gai

Role: CONTACT

972 8 9406472

Facility Contacts

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Wim Janssens

Role: primary

003216340957

Joni Niskanen

Role: primary

00358 3 3116 3130

Minttu Kopra

Role: backup

00358444722863

Gerry McElvaney

Role: primary

0035318093763

Prof. Jan Stolk, MD PhD

Role: primary

0031 71 526 2950

Role: backup

Rob Janssen

Role: primary

0031243658755

Role: backup

0031243657944

Hanan Tanash

Role: primary

0046040332180

Louise Qvist

Role: backup

0046040337574

Alice Turner

Role: primary

00441213713886

Anita Pye

Role: backup

00441213713886

Gourab Choudhury

Role: primary

00441312422064

Eleni Koullia

Role: backup

Aishath Fazleen

Role: primary

00442381206397

Ruben Magalhaes

Role: backup

004423 8120 4479

References

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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.

Reference Type DERIVED
PMID: 37665565 (View on PubMed)

Other Identifiers

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Kamada-AAT (inhaled) 008

Identifier Type: -

Identifier Source: org_study_id

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