NCT06512454 · Takeda
A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems
(ALPHATUDE)
What this study is about
The main aim of this study is to learn about liver problems caused by the lack of alpha-1 antitrypsin (called Alpha-1 Antitrypsin Deficiency or AATD) in adults when not treated (this is called the natural history of a condition) over 5 years.
View original scientific description
The main aim of this study is to learn about liver problems caused by the lack of alpha-1 antitrypsin (called Alpha-1 Antitrypsin Deficiency or AATD) in adults when not treated (this is called the natural history of a condition) over 5 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 hospital care, and describe how the AATD also affects and 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 completed questionnaires (called patient-reported outcomes or PRO).
Interventions
OTHER
No Intervention
This is a non-interventional study.
Primary outcome measures
Number of Participants With Liver Disease Progression
Time frame: Baseline up to 5 years
Liver disease progression will be defined as advancement in greater than or equal to (\>=1) fibrosis stage: example any progression from fibrosis stage (F)0 to F1, 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, or d) receipt of a liver transplant MELD score increase, or d) 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 5 years
Time to liver disease progression is defined as time to advancement in \>=1 fibrosis stage (example 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 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 5 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 decompensating event or liver transplant and first to second decompensating event and all subsequent decompensating events or liver transplant. 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 5 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 decompensating event or liver transplant and first to second decompensating event and all subsequent decompensating events or liver transplant. 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 5 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 5 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 5 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 5 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Participants who meet all the following criteria will be included in the study. Cohorts 1 and 2:
- Willing to provide written informed consent or currently enrolled in an ongoing participating AATD patient registry that does not require reconsenting 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). • 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, as determined through:
- Lab and imaging measures to define liver disease manifestation
Exclusion criteria
- 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), fibro scan (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.
- Participants who had previously been treated or in an active participation in an interventional trial studying liver or lung disease.
- Treatment with liver directed AATD investigational therapy as part of a compassionate use request.
Where
- Gainesville, Florida
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Oct 24, 2025 · Source of record for eligibility and locations