Recruiting

Alpha-1 Antitrypsin Deficiency

Sponsor:

Takeda

Code:

NCT06512454

Conditions

Alpha1-Antitrypsin Deficiency

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

No Intervention

Study Details

Brief 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). 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

Study ID

NCT06512454

Start date

Sep 25, 2024

Status verified date

Jul, 2026

Completion date

Dec 31, 2031

Anticipated

Primary completion date

Dec 31, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 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 or imaging measures.

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), 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).
4. 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).

Study Design

Enrollment

500 participants

Anticipated

Interventions and Outcome Measures

Arms

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.

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.

Interventions

No Intervention

This is an observational study.

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Takeda Contact

+1-877-825-3327medinfoUS@takeda.com

Locations

University of Florida

Recruiting

Gainesville, Florida, United States, 32608

Contacts

Site Contact

Virginia.Clark@medicine.ufl.edu

Principal Investigator:

Virginia Clark

University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Site Contact

strangec@musc.edu

Principal Investigator:

Charlie Strange

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37212

Contacts

Site Contact

suzanne.sharpton@vumc.org

Principal Investigator:

Suzanne Sharpton

More Information

Sponsor

Takeda

Last update posted

Jul 24, 2026

Last verified

Jul, 2026

Keywords

  • Natural History

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Takeda on 2026-07-24.