A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems
NCT Number: NCT06512454
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Alpha1-Antitrypsin Deficiency
Interventions: OTHER: No Intervention
Sponsor: Takeda
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 1000
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09-10
Completion Date: 2032-04-06

Summary:
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).

Primary Outcome Measures: 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 (F) 1 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., Baseline up to 5 years|Time to Liver Disease Progression, 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., Baseline up to 5 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 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., Baseline up to 5 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 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., Baseline up to 5 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., Baseline up to 5 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., Baseline up to 5 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., Baseline up to 5 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., Baseline up to 5 years
Secondary Outcome Measures: 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)., Baseline up to 5 years|Proportion of Participants With Lung Disease at Baseline who Experience Lung Disease Progression at 5 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 \[DLCO\])., Baseline up to 5 years|Number of Participants With Invasive and Non-Invasive Assessment for Liver Disease, Baseline up to 5 years