A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems

Официальное название

Prospective Observational Study on the Natural History of Alpha-1 Antitrypsin Deficiency and Associated Liver Disease

Обзор

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).

Вмешательства

• Другое No Intervention
  This is an observational study.

Первичные конечные точки

• Number of Participants With Liver Disease Progression [Срок оценки: Baseline up to 8 years]
• Time to Liver Disease Progression [Срок оценки: Baseline up to 8 years]
• Time to Liver Disease Trajectory [Срок оценки: Baseline up to 8 years]
• Probability of Transition in Liver Disease Trajectory [Срок оценки: Baseline up to 8 years]
• Percentage of Participants With Disease Regression [Срок оценки: Baseline up to 8 years]
• Time to Liver Disease Regression [Срок оценки: Baseline up to 8 years]
• Percentage of Participants With All-cause Mortality and Cause-specific Mortality [Срок оценки: Baseline up to 8 years]
• Time to Death (All-causes) and Cause-specific Death (Liver Disease-specific Causes) [Срок оценки: Baseline up to 8 years]

Вторичные конечные точки (3)

• Percentage of Participants Who Develop Lung Disease [Срок оценки: Baseline up to 8 years]
• Proportion of Participants With Lung Disease at Baseline who Experience Lung Disease Progression at 4-8 Years [Срок оценки: Baseline up to 8 years]
• Characterize Diagnostic and Monitoring Patterns for Liver Disease (Invasive and Non-invasive Assessments) [Срок оценки: Baseline up to 8 years]

Критерии участия

Критерии включения

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).

• 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.

Критерии исключения

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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 3 центра

• University of Florida — Gainesville
• University of South Carolina — Charleston
• Vanderbilt University Medical Center — Nashville

Австрия · 1 центр

• Vienna General Hospital (AKH Wien) — Vienna

Германия · 1 центр

• Universitätsklinikum Aachen — Aachen

Ирландия · 1 центр

• Beaumont Hospital — Dublin

Испания · 1 центр

• Hospital Universitari Vall d'Hebron — Barcelona

Великобритания · 1 центр

• Queen Elizabeth Hospital Birmingham — Birmingham

Идентификаторы

NCT: NCT06512454 · TAK-999-5008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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