Clinical trial NCT06512454: A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems
Official title: Prospective Observational Study on the Natural History of Alpha-1 Antitrypsin Deficiency and Associated Liver Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alpha1-Antitrypsin Deficiency
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2024-07-22
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants who have already been diagnosed with AATD of genotype/phenotype Pi\*ZZ, with mild or without liver disease manifestation, or with genotype/phenotype of Pi\*SZ with moderate-advanced or severe liver disease manifestation undergoing routine clinical care will be enrolled.

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Liver Disease Progression
timeFrame: Baseline up to 5 years
measure: Time to Liver Disease Progression
timeFrame: Baseline up to 5 years
measure: Time to Liver Disease Trajectory
timeFrame: Baseline up to 5 years
measure: Probability of Transition in Liver Disease Trajectory
timeFrame: Baseline up to 5 years
measure: Percentage of Participants With Disease Regression
timeFrame: Baseline up to 5 years
measure: Time to Liver Disease Regression
timeFrame: Baseline up to 5 years
measure: Percentage of Participants With All-cause Mortality and Cause-specific Mortality
timeFrame: Baseline up to 5 years
measure: Time to Death (All-causes) and Cause-specific Death (Liver Disease-specific Causes)
timeFrame: Baseline up to 5 years
Secondary outcomes:
measure: Percentage of Participants Who Develop Lung Disease
timeFrame: Baseline up to 5 years
measure: Proportion of Participants With Lung Disease at Baseline who Experience Lung Disease Progression at 5 Years
timeFrame: Baseline up to 5 years
measure: Number of Participants With Invasive and Non-Invasive Assessment for Liver Disease
timeFrame: Baseline up to 5 years
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen AöR
state: North Rhine-Westphalia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: