Alpha1-Antitrypsin DeficiencyALPHATUDENCT06512454
A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems
An observational study of Alpha1-Antitrypsin Deficiency, run by Takeda at 8 sites in 6 countries.
Trial summary
The liver produces a protein called alpha-1 antitrypsin (AAT). AAT is normally released into the bloodstream. In some people, the liver makes an abnormal version of AAT, called Z-AAT. Z-AAT builds up in liver cells and also leads to low blood levels of AAT (called Alpha-1 Antitrypsin Deficiency or AATD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alpha1-Antitrypsin Deficiency
- How many people
- 500 participants
- Where
- 8 sitesin 6 countries
- Study dates
- 25 Sep 2024to 31 Dec 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants who have already been diagnosed with AATD of genotype/phenotype Pi*ZZ, with or without liver disease manifestation (F0-F4dc), or with genotype/phenotype of Pi*SZ with moderate-advanced or severe liver disease manifestation (F2-F4dc).
Who may be able to join
- Participants who meet all the following criteria will be included in the study.
- Cohorts 1 and 2:
- Willing to provide written informed consent to participate in the study.
- >=18 years of age at enrollment in this study.
- Participants with documented diagnosis of AATD, meeting the following criteria:
- Cohort 1 (AATD-Pi*ZZ genotype/phenotype).
Show all 10Show fewer
- Pi*ZZ genotype as documented from rapid genetic assay, sequencing, or polymerase chain reaction (PCR), or Pi*ZZ phenotype as documented from iso-electric focusing (IEF) electrophoresis.
- Cohort 2 (AATD-Pi*SZ genotype/phenotype with liver disease manifestation).
- Pi*SZ genotype as documented from rapid genetic assay, sequencing, or PCR, or Pi*SZ phenotype as documented from IEF electrophoresis, and
- Moderate-advanced or severe liver disease manifestation as defined by either liver biopsy or surrogate laboratory or imaging measures.
Who cannot join
- Participants who meet any following criteria will be excluded from the study.
- Documented AATD genotype/phenotype other than Pi*ZZ or Pi*SZ.
- History of liver transplant.
- No results for either biopsies, magnetic resonance elastography (MRE), FibroScan (vibration controlled transient elastography [VCTE]), or Aspartate aminotransferase to platelet ratio index (APRI) in the 24 months prior to the index/enrollment date and has none of these tests ordered during the index period (i.e., index date +90 days).
- Participants with prior participation in an interventional clinical trial evaluating liver or lung disease, or who have received an investigational AATD-directed therapy under a compassionate use program, will be excluded if they do not present one of the following:
- A minimum washout period of 6 months has elapsed since the last dose of the investigational product.
- A history of having received placebo in prior interventional trials (to be evaluated on a case-by-case basis).
Trial locations and contacts
8 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 6 countries
United States3 sites, 3 recruiting
- Recruiting
University of South Carolina
Charleston, South Carolina, 29425
Site Contact, strangec@musc.edu
Charlie Strange
- Recruiting
University of Florida
Gainesville, Florida, 32608
Site Contact, Virginia.Clark@medicine.ufl.edu
Virginia Clark
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
Site Contact, suzanne.sharpton@vumc.org
Suzanne Sharpton
Austria1 site, 1 recruiting
- Recruiting
Vienna General Hospital (AKH Wien)
Vienna, 1090
Site Contact, mattias.mandorfer@meduniwien.ac.at
Mattias Mandorfer
Germany1 site, 1 recruiting
- Recruiting
Universitätsklinikum Aachen
Aachen, 52074
Site Contact, pstrnad@ukaachen.de
Pavel Strnad
Ireland1 site, 1 recruiting
- Recruiting
Beaumont Hospital
Dublin, Dublin 9
Site Contact, gmcelvaney@rcsi.ie
Gerry McElvaney
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona
Site Contact, monica.pons@vhir.org
Monica Pons Delgado
United Kingdom1 site, 1 recruiting
- Recruiting
Queen Elizabeth Hospital Birmingham
Birmingham, B15 2GW
Site Contact, a.m.turner@bham.ac.uk
Alice Turner
About this study
Official title: Prospective Observational Study on the Natural History of Alpha-1 Antitrypsin Deficiency and Associated Liver Disease
The liver produces a protein called alpha-1 antitrypsin (AAT). AAT is normally released into the bloodstream. In some people, the liver makes an abnormal version of AAT, called Z-AAT. Z-AAT builds up in liver cells and also leads to low blood levels of AAT (called Alpha-1 Antitrypsin Deficiency or AATD). Over time, this build up leads to different stages of liver problems, if not treated. This is called natural history of AATD.
The main aim of this study is to learn about liver problems caused by AATD in adults when not treated over 4 to 8 years. Other aims are to learn what can predict the AATD-liver condition starting and getting better or worse, describe how this condition is currently being diagnosed and watched in normal care, and describe how the AATD also affects an adult's lung function.
Data in this study will be collected to include medical history of a participant, including the date AATD was first identified and/or the date on which the first AATD-related liver or lung problems were diagnosed. At study start and then every year until study end, participants will be asked to complete questionnaires (called patient-reported outcomes or PROs).
- Conditions
- Alpha1-Antitrypsin Deficiency
- Being tested
- No Intervention
- Keywords
- Natural History
- 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.
No InterventionOther
This is an observational study.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: AATD-Pi*ZZ Genotype/Phenotype | Participants who have been diagnosed with Alpha-1 Antitrypsin Deficiency homozygous ZZ (AATD-Pi*ZZ) genotype/phenotype with or without liver disease manifestations (fibrosis- F0-F4dc) will be enrolled and data will be prospectively collected per routine care throughout the follow-up period. Receives: Other: No Intervention | |
| Cohort 2: AATD-Pi*SZ Genotype/Phenotype | Participants who have been diagnosed with alpha-1 antitrypsin deficiency heterozygous SZ (AATD-Pi*SZ) genotype/phenotype with moderate-advanced or severe liver disease (F2-F4dc) manifestations will be enrolled and data will be prospectively collected per routine care throughout the follow-up period. Receives: Other: No Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Liver Disease Progression
Liver disease progression will be defined as advancement in greater than or equal to (>=)1 fibrosis stage: example any progression from fibrosis stage F0/F1 to F2, F1 to F2, F2 to F3 etc. and/or occurrence of any of these composite events: a) advancement in >=1 fibrosis stage, b) development of a liver disease-related clinical event, c) model for end-stage liver disease (MELD) score increase, d) newly added on liver transplant list, e) receipt of a liver transplant. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Measured: Baseline up to 8 years
Time to Liver Disease Progression
Time to liver disease progression is defined as time to advancement in >=1 fibrosis stage (example F0/F1 to F2, F2 to F3 etc.) and/or time to the earliest of: Advancement in >=1 fibrosis stage, or development of a liver disease-related clinical event, or MELD score increase or receipt/newly added to transplant list of a liver transplant. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Measured: Baseline up to 8 years
Time to Liver Disease Trajectory
Time to liver disease trajectory is defined as time of transition from F0/F1 to F2, F2 to F3, F3 to F4, F4 to the first decompensating event or liver transplant/listing and first to second decompensating event and all subsequent decompensating events or liver transplant/listing. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Measured: Baseline up to 8 years
Probability of Transition in Liver Disease Trajectory
Probability of liver disease trajectory is defined as probability of transition from F0/F1 to F2, F2 to F3, F3 to F4, F4 to the first decompensating event or liver transplant/listing and first to second decompensating event and all subsequent decompensating events or liver transplant/listing. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Measured: Baseline up to 8 years
Percentage of Participants With Disease Regression
Disease regression is defined as decrease in >=1 fibrosis staging. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Measured: Baseline up to 8 years
Time to Liver Disease Regression
Time to liver disease regression is defined as time to decrease in >=1 fibrosis stage. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Measured: Baseline up to 8 years
Percentage of Participants With All-cause Mortality and Cause-specific Mortality
Cause-specific mortality is defined as mortality due to liver failure or complications of cirrhosis/portal hypertension or hepatocellular carcinoma, or infections secondary to liver failure.
Measured: Baseline up to 8 years
Time to Death (All-causes) and Cause-specific Death (Liver Disease-specific Causes)
Cause-specific mortality is defined as mortality due to liver failure or complications of cirrhosis/portal hypertension or hepatocellular carcinoma, or infections secondary to liver failure.
Measured: Baseline up to 8 years
Secondary outcomes (3)
Percentage of Participants Who Develop Lung Disease
Development of lung disease will be defined as either a forced expiratory volume in 1 second (FEV1) percent (%) predicted of less than (<) 70% or the diagnosis of at least 1 lung condition (chronic obstructive pulmonary disease [COPD], emphysema, bronchiectasis, chronic bronchitis) over the study duration or at specific timepoints.
Measured: Baseline up to 8 years
Proportion of Participants With Lung Disease at Baseline who Experience Lung Disease Progression at 4-8 Years
Lung disease progression is defined as changes in pulmonary function (defined as >=10% absolute change in FEV1, forced vital capacity [FVC], or diffusing capacity of the lungs for carbon monoxide [DLCO]) over the study duration or at specific timepoints.
Measured: Baseline up to 8 years
Characterize Diagnostic and Monitoring Patterns for Liver Disease (Invasive and Non-invasive Assessments)
Measured: Baseline up to 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2024
- Study start25 Sep 2024
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha1-Antitrypsin DeficiencyStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06512454
- Sponsor's protocol ID
- TAK-999-5008
- Acronym
- ALPHATUDE
- Status last verified
- Jul 2026
- First submitted
- 16 Jul 2024
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Observational Study on the Natural History of Alpha-1 Antitrypsin Deficiency and Associated Liver Disease
- ClinicalTrials.gov ID
- NCT06512454
- Acronym / sponsor ID
- ALPHATUDE / TAK-999-5008
- Conditions
- Alpha1-Antitrypsin Deficiency
- Keywords
- Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2024 (actual)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 22 Jul 2024 (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 liver produces a protein called alpha-1 antitrypsin (AAT). AAT is normally released into the bloodstream. In some people, the liver makes an abnormal version of AAT, called Z-AAT. Z-AAT builds up in liver cells and also leads to low blood levels of AAT (called Alpha-1 Antitrypsin Deficiency or AATD). Over time, this build up leads to different stages of liver problems, if not treated. This is called natural history of AATD.
The main aim of this study is to learn about liver problems caused by AATD in adults when not treated over 4 to 8 years. Other aims are to learn what can predict the AATD-liver condition starting and getting better or worse, describe how this condition is currently being diagnosed and watched in normal care, and describe how the AATD also affects an adult's lung function.
Data in this study will be collected to include medical history of a participant, including the date AATD was first identified and/or the date on which the first AATD-related liver or lung problems were diagnosed. At study start and then every year until study end, participants will be asked to complete questionnaires (called patient-reported outcomes or PROs).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: AATD-Pi*ZZ Genotype/Phenotype | – | Other: No InterventionParticipants who have been diagnosed with Alpha-1 Antitrypsin Deficiency homozygous ZZ (AATD-Pi*ZZ) genotype/phenotype with or without liver disease manifestations (fibrosis- F0-F4dc) will be enrolled and data will be prospectively collected per routine care throughout the follow-up period. |
| Cohort 2: AATD-Pi*SZ Genotype/Phenotype | – | Other: No InterventionParticipants who have been diagnosed with alpha-1 antitrypsin deficiency heterozygous SZ (AATD-Pi*SZ) genotype/phenotype with moderate-advanced or severe liver disease (F2-F4dc) manifestations will be enrolled and data will be prospectively collected per routine care throughout the follow-up period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants who have already been diagnosed with AATD of genotype/phenotype Pi*ZZ, with or without liver disease manifestation (F0-F4dc), or with genotype/phenotype of Pi*SZ with moderate-advanced or severe liver disease manifestation (F2-F4dc).
Key inclusion criteria (10 listed)
- Participants who meet all the following criteria will be included in the study.
- Willing to provide written informed consent to participate in the study.
- >=18 years of age at enrollment in this study.
- Participants with documented diagnosis of AATD, meeting the following criteria:
Key exclusion criteria (7 listed)
- Participants who meet any following criteria will be excluded from the study.
- Documented AATD genotype/phenotype other than Pi*ZZ or Pi*SZ.
- History of liver transplant.
- No results for either biopsies, magnetic resonance elastography (MRE), FibroScan (vibration controlled transient elastography [VCTE]), or Aspartate aminotransferase to platelet ratio index (APRI) in the 24 months prior to the index/enrollment date and has none of these tests ordered during the index period (i.e., index date +90 days).
- Participants with prior participation in an interventional clinical trial evaluating liver or lung disease, or who have received an investigational AATD-directed therapy under a compassionate use program, will be excluded if they do not present one of the following:
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 |
|---|---|---|
| No InterventionThis is an observational study. | Other | Cohort 1: AATD-Pi*ZZ Genotype/Phenotype, Cohort 2: AATD-Pi*SZ Genotype/Phenotype |
Primary outcome
Number of Participants With Liver Disease Progression
Time frame: Baseline up to 8 years
Liver disease progression will be defined as advancement in greater than or equal to (>=)1 fibrosis stage: example any progression from fibrosis stage F0/F1 to F2, F1 to F2, F2 to F3 etc. and/or occurrence of any of these composite events: a) advancement in >=1 fibrosis stage, b) development of a liver disease-related clinical event, c) model for end-stage liver disease (MELD) score increase, d) newly added on liver transplant list, e) receipt of a liver transplant. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Time to Liver Disease Progression
Time frame: Baseline up to 8 years
Time to liver disease progression is defined as time to advancement in >=1 fibrosis stage (example F0/F1 to F2, F2 to F3 etc.) and/or time to the earliest of: Advancement in >=1 fibrosis stage, or development of a liver disease-related clinical event, or MELD score increase or receipt/newly added to transplant list of a liver transplant. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Time to Liver Disease Trajectory
Time frame: Baseline up to 8 years
Time to liver disease trajectory is defined as time of transition from F0/F1 to F2, F2 to F3, F3 to F4, F4 to the first decompensating event or liver transplant/listing and first to second decompensating event and all subsequent decompensating events or liver transplant/listing. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Probability of Transition in Liver Disease Trajectory
Time frame: Baseline up to 8 years
Probability of liver disease trajectory is defined as probability of transition from F0/F1 to F2, F2 to F3, F3 to F4, F4 to the first decompensating event or liver transplant/listing and first to second decompensating event and all subsequent decompensating events or liver transplant/listing. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Percentage of Participants With Disease Regression
Time frame: Baseline up to 8 years
Disease regression is defined as decrease in >=1 fibrosis staging. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Time to Liver Disease Regression
Time frame: Baseline up to 8 years
Time to liver disease regression is defined as time to decrease in >=1 fibrosis stage. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Percentage of Participants With All-cause Mortality and Cause-specific Mortality
Time frame: Baseline up to 8 years
Cause-specific mortality is defined as mortality due to liver failure or complications of cirrhosis/portal hypertension or hepatocellular carcinoma, or infections secondary to liver failure.
Time to Death (All-causes) and Cause-specific Death (Liver Disease-specific Causes)
Time frame: Baseline up to 8 years
Cause-specific mortality is defined as mortality due to liver failure or complications of cirrhosis/portal hypertension or hepatocellular carcinoma, or infections secondary to liver failure.
3 secondary outcomes
Percentage of Participants Who Develop Lung Disease
Time frame: Baseline up to 8 years
Proportion of Participants With Lung Disease at Baseline who Experience Lung Disease Progression at 4-8 Years
Time frame: Baseline up to 8 years
Characterize Diagnostic and Monitoring Patterns for Liver Disease (Invasive and Non-invasive Assessments)
Time frame: Baseline up to 8 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- To obtain more information about this study, click this linkLink provided by the sponsor.
- Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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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.
Study Director study director
Takeda
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alpha1-Antitrypsin Deficiency, run by Takeda at 8 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 7 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: looking for participants now, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Austria, Germany, Ireland, Spain 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Takeda Contact (+1-877-825-3327, medinfoUS@takeda.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Liver Disease Progression (time frame: Baseline up to 8 years). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jul 2026.