Alpha 1-Antitrypsin DeficiencyPhase 3InnovAATeNCT04204252
Phase III, Efficacy and Safety of "Kamada-AAT for Inhalation"
A Phase 3 study testing Alpha 1-Antitrypsin in people with Alpha 1-Antitrypsin Deficiency, run by Kamada, Ltd. at 9 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alpha 1-Antitrypsin Deficiency
- What is being tested?
- Alpha 1-Antitrypsin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 9 sitesin 6 countries
- Study dates
- 25 Nov 2019to 27 Feb 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- 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.
- 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.
- Inability to attend scheduled clinic visits and/or comply with study protocol.
- 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
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
United Kingdom3 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW
Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD
Netherlands2 sites
Leiden University Medical Center (LUMC)
Leiden, ZA, 2333ZA
Canisius Wilhelmina Hospital (CWZ)
Nijmegen, 6532SZ
About this study
Official title: 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:
Read more
- 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.
Read the detailed description
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
- Alpha 1-Antitrypsin Deficiency
- Being tested
- Alpha 1-Antitrypsin, Placebo
- Keywords
- Alpha 1 Antitrypsin, Inhaled Alpha 1 Antitrypsin, Nebulizer
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha 1-AntitrypsinDrug
Also called Kamada alpha 1-antitrypsin for inhalation
Kamada's alpha 1-antitrypsin product given by inhalation using the eFlow® electronic nebulizer manufactured by PARI Pharma GmbH
PlaceboDrug
Preparation of NaCl in phosphate buffer solution with 0.01% TWEEN-80
| Study group | Role | What they receive |
|---|---|---|
| Inhaled AAT | Active comparator | Daily inhalation of 80 mg/day "Kamada-AAT for Inhalation" for 104 weeks Receives: Drug: Alpha 1-Antitrypsin |
| Placebo | Placebo comparator | Daily inhalation of a solution of NaCl in phosphate buffer solution with 0.01% TWEEN-80 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
FEV1 post bronchodilator
Change from baseline in post bronchodilator FEV1 at 104 weeks
Measured: 104 weeks
Secondary outcomes (5)
CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).
Change from baseline over 104 weeks of treatment in CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).
Measured: 104 weeks
FEV1 % of predicted
Change from baseline over 104 weeks of treatment in FEV1 % of predicted
Measured: 104 weeks
FEV1/FVC %
Change from baseline over 104 weeks of treatment in FEV1/FVC %
Measured: 104 weeks
Exacerbations
Annual rate of exacerbations by severity and duration
Measured: 104 weeks
6 minute walk test
Change from Baseline in the distance walked in six minutes
Measured: 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start25 Nov 2019
- Primary completion19 Feb 2026
- Study completion27 Feb 2026
Why it stopped: Following interim analysis for futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alpha 1-Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kamada, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Responsible party
- Sponsor
- Investigators
- Jan Stolk, Prof, Principal investigator, LUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04204252
- Sponsor's protocol ID
- Kamada-AAT (inhaled) 008
- Acronym
- InnovAATe
- Status last verified
- Jun 2026
- First submitted
- 17 Dec 2019
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37665565
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04204252
- Acronym / sponsor ID
- InnovAATe / Kamada-AAT (inhaled) 008
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Keywords
- Alpha 1 Antitrypsin, Inhaled Alpha 1 Antitrypsin, Nebulizer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Following interim analysis for futility
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Kamada, Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Study start
- 25 Nov 2019 (actual)
- Primary completion
- 19 Feb 2026 (actual)
- Study completion
- 27 Feb 2026 (actual)
- First posted
- 18 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Inhaled AAT | Active comparator | Drug: Alpha 1-AntitrypsinDaily inhalation of 80 mg/day "Kamada-AAT for Inhalation" for 104 weeks |
| Placebo | Placebo comparator | Drug: PlaceboDaily inhalation of a solution of NaCl in phosphate buffer solution with 0.01% TWEEN-80 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (20 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alpha 1-AntitrypsinAlso: Kamada alpha 1-antitrypsin for inhalationKamada's alpha 1-antitrypsin product given by inhalation using the eFlow® electronic nebulizer manufactured by PARI Pharma GmbH | Drug | Inhaled AAT |
| PlaceboPreparation of NaCl in phosphate buffer solution with 0.01% TWEEN-80 | Drug | Placebo |
Primary outcome
FEV1 post bronchodilator
Time frame: 104 weeks
Change from baseline in post bronchodilator FEV1 at 104 weeks
5 secondary outcomes
CT densitometry whole-lung 15th percentile lung density (PD15) at total lung capacity (TLC).
Time frame: 104 weeks
FEV1 % of predicted
Time frame: 104 weeks
FEV1/FVC %
Time frame: 104 weeks
Exacerbations
Time frame: 104 weeks
6 minute walk test
Time frame: 104 weeks
Results and safety
The study was stopped early (reason given: Following interim analysis for futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Derived from this study: PubMed 37665565Kappe 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Stolk, Prof principal investigator
LUMC
9 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alpha 1-Antitrypsin in people with Alpha 1-Antitrypsin Deficiency, run by Kamada, Ltd. at 9 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom, Netherlands, Belgium, Finland, Ireland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Following interim analysis for futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FEV1 post bronchodilator (time frame: 104 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04204252, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.