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

NCT03946449 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: AROAAT20022019-000068-86
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the the safety and efficacy of the investigational product, fazirsiran (TAK-999, ARO-AAT), administered subcutaneously to patients with alpha-1 antitrypsin deficiency associated liver disease (AATD).

Conditions

Alpha 1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b

  Baseline, Week 24

• Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 48: Cohort 2

  Baseline, Week 48

Secondary Outcomes (25)

• Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b

  Baseline, Weeks 2, 4, 6, 16, 24

• Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2

  Baseline, Weeks 2, 4, 6, 16, 22, 28, 34, 40, 48

• Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b

  Baseline (Day 1), Day 2, Week 2, Week 4, Week 4 (24-48h post dose), Week 6, Week 16, Week 16 (24/48h post dose), Week 24

• ALT Values Over Time: Cohort 2

  Baseline (Day 1), Day 2, Week 2, Week 4, Week 4 (24-48h post dose), Week 6, Week 16, Week 16 (24/48h post dose), Week 22, Week 28, Week 34, Week 40, Week 48

• Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b

  Baseline (Day 1), Day 2, Week 2, Week 4, Week 4 (24-48h post dose), Week 6, Week 16, Week 16 (24/48h post dose), Week 24

Study Arms (3)

ARO-AAT 100 mg Cohort 1b

EXPERIMENTAL

Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous AROAAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W.

Drug: ARO-AAT

ARO-AAT 200 mg Cohort 1

EXPERIMENTAL

Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous AROAAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.

Drug: ARO-AAT

ARO-AAT 200 mg Cohort 2

EXPERIMENTAL

Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous AROAAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.

Drug: ARO-AAT

Interventions

ARO-AAT DRUG

solution for subcutaneous injection

Also known as: Fazirsiran Injection, TAK-999

ARO-AAT 100 mg Cohort 1b; ARO-AAT 200 mg Cohort 1; ARO-AAT 200 mg Cohort 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AATD
• Liver biopsy indicating Metavir F1-F3 liver fibrosis based on local pathology read.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (4)

Research Center 1

Vienna, 1090, Austria

Location

Research Center 1

Aachen, 52074, Germany

Location

Research Center 3

Cambridge, CB2 0QQ, United Kingdom

Location

Research Center 2

Edinburgh, EH19 3BJ, United Kingdom

Location

Related Publications (1)

• Strnad P, Mandorfer M, Choudhury G, Griffiths W, Trautwein C, Loomba R, Schluep T, Chang T, Yi M, Given BD, Hamilton JC, San Martin J, Teckman JH. Fazirsiran for Liver Disease Associated with Alpha1-Antitrypsin Deficiency. N Engl J Med. 2022 Aug 11;387(6):514-524. doi: 10.1056/NEJMoa2205416. Epub 2022 Jun 25.

  PMID: 35748699 DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Operating Officer
• Organization: Arrowhead Pharmaceuticals, Inc.

info@arrowheadpharma.com

1 (626) 304-3400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 10, 2019
• Study Start: October 31, 2019
• Primary Completion: April 28, 2022
• Study Completion: December 14, 2023
• Last Updated: October 15, 2025
• Results First Posted: April 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); GB (2); AU (1)