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

Takeda

Status: Enrolling

Conditions: Alpha1-Antitrypsin Deficiency

Treatments: Other: No Intervention

Study type: Observational

Funder types: Industry

Identifiers

NCT06512454

TAK-999-5008

Details and patient eligibility

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. 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).

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants who meet all the following criteria will be included in the study.

Cohorts 1 and 2:

1. 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.

2. >=18 years of age at enrollment in this study.

3. Participants with documented diagnosis of AATD, meeting the following criteria:

   1. 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.

   2. 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 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.

1. Documented AATD genotype/phenotype other than Pi*ZZ or Pi*SZ.
2. History of liver transplant.
3. 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 study baseline date, and has none of these tests ordered in the current visit that will be available in the next 90 days.
4. Participants who had previously been treated or in an active participation in an interventional trial studying liver or lung disease.
5. Treatment with liver directed AATD investigational therapy as part of a compassionate use request.

Trial design

1,000 participants in 2 patient groups

Cohort 1: AATD-Pi*ZZ Genotype/Phenotype

Description:

Participants who have been diagnosed with Alpha-1 Antitrypsin Deficiency homozygote ZZ (AATD-Pi\*ZZ) genotype/phenotype with mild or without liver disease manifestations will be enrolled and data will be prospectively collected per routine care throughout the follow-up period (up to 5 years).

Treatment:

Other: No Intervention

Cohort 2: AATD-Pi*SZ Genotype/Phenotype

Description:

Participants who have been diagnosed with alpha-1 antitrypsin deficiency heterozygous SZ (AATD-Pi\*SZ) genotype/phenotype with moderate-advanced or severe liver disease manifestations will be enrolled and data will be prospectively collected per routine care throughout the follow-up period (up to 5 years).

Treatment:

Other: No Intervention