Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)

• Register: ClinicalTrials.gov
• Last refreshed on: 13 June 2023
• Main ID: NCT03946449
• Date of registration: 08/05/2019
• Prospective Registration: Yes
• Primary sponsor: Arrowhead Pharmaceuticals
• Public title: Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)
• Scientific title: A Pilot Open Label, Multi-dose, Phase 2 Study to Assess the Safety and Efficacy of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)
• Date of first enrolment: December 19, 2019
• Target sample size: 16
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03946449
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Austria, Germany, United Kingdom

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of AATD

- Women of childbearing potential must have a negative pregnancy test, cannot be breast
feeding, and must be willing to use contraception

- Willing to provide written informed consent and to comply with study requirements

- Non-smoker for at least 1 year

- No abnormal finding of clinical relevance at screening

Exclusion Criteria:

- Clinically significant health concerns other than AATD

- Previous diagnosis or diagnosis at Screening of definitive liver cirrhosis

- Regular use of alcohol within one month prior to Screening

- Use of an investigational agent or device within 30 days prior to dosing or current
participation in an investigational study involving therapeutic intervention

- Use of illicit drugs within 1 year prior to Screening

Note: additional inclusion/exclusion criteria may apply, per protocol



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alpha 1-Antitrypsin Deficiency

Intervention(s)

Drug: Fazirsiran Injection (TAK-999, ARO-AAT)

Primary Outcome(s)

Change From Baseline Over Time in Total, Soluble, and Insoluble Z-Alpha 1 Antitrypsin (Z-AAT) Liver Concentrations [Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44]

Secondary Outcome(s)

Change From Baseline Over Time in Hepatic Stiffness based on FibroScan (when available) [Time Frame: Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Weeks 44 and 140]

Change From Baseline Over Time in Fibrosis-4 Index (FIB4) [Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140]

Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment [Time Frame: Up to Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: up to Extension Week 140]

Change From Baseline Over Time in Alanine Transaminase (ALT) [Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140]

Change From Baseline Over Time in Histological Metrics of Liver Disease: Steatosis Score [Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44]

Change From Baseline Over Time in Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Score [Time Frame: Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44]

Incidence of Anti-Drug Antibodies (ADAs) to Fazirsiran [Time Frame: Day 1, Week 6, and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Weeks 24 and 44]

Change From Baseline Over Time in Aspartate Transaminase (AST) to Platelet Ratio Index (APRI) [Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140]

Change From Baseline Over Time in Circulating Levels of Z-AAT [Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or through Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140]

Change From Baseline Over Time in Gamma-Glutamyl Transferase (GGT) [Time Frame: Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Weeks 44 and 140]

Change From Baseline Over Time in Histological Metrics of Liver Disease: Hepatocyte Cell Death Score [Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44]

Change From Baseline Over Time in Histological Metrics of Liver Disease: Inflammation Score [Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44]

Change From Baseline Over Time in Plasma Collagen Type 3 (PRO-C3) [Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140]

Titers of Anti-Drug Antibodies (ADAs) to Fazirsiran [Time Frame: Day 1, Week 6, and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Weeks 24 and 44]

Secondary ID(s)

2019-000068-86

AROAAT2002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors