Alpha 1-Antitrypsin DeficiencyPhase 2NCT03946449

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

A Phase 2 study testing ARO-AAT in people with Alpha 1-Antitrypsin Deficiency, run by Arrowhead Pharmaceuticals at 4 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Alpha 1-Antitrypsin Deficiency
What is being tested?: ARO-AAT
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 4 sitesin 3 countries
Study dates: 31 Oct 2019to 14 Dec 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

4 sites in 3 countries.

Country

City, postcode or hospital

4 sites in 3 countries

United Kingdom2 sites

Research Center 3
Cambridge, CB2 0QQ
Research Center 2
Edinburgh, EH19 3BJ

Other trials in United Kingdom

Austria1 site

Research Center 1
Vienna, 1090

Other trials in Austria

Germany1 site

Research Center 1
Aachen, 52074

Other trials in Germany

About this study

Official 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)

Read the detailed description

Participants will be enrolled to receive multiple subcutaneous injections of fazirsiran (TAK-999, ARO-AAT). All eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. All participants will undergo an end of study (EOS) biopsy. Treated participants will be offered the opportunity to continue treatment in an open label extension during which they will undergo a final biopsy.

Conditions: Alpha 1-Antitrypsin Deficiency
Being tested: ARO-AAT
Medical subject headings: alpha 1-Antitrypsin Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ARO-AATDrug
Also called Fazirsiran Injection, TAK-999
solution for subcutaneous injection

Study groups in NCT03946449
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: ARO-AAT

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b
Measured: 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
Measured: Baseline, Week 48

Secondary outcomes (25)

Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b
Measured: Baseline, Weeks 2, 4, 6, 16, 24
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Measured: Baseline, Weeks 2, 4, 6, 16, 22, 28, 34, 40, 48
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Measured: 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
Measured: 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
Measured: 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
GGT Values Over Time: Cohort 2
Measured: 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
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
The FIB 4 score evaluates the degree of fibrosis in patients suspected of or already diagnosed with hepatic fibrosis. FIB-4 is calculated as (Age (years) * aspartate aminotransferase) / (platelets * √(ALT)).
The result provided from the above equation is interpreted according to 2 cut off values: FIB 4 <1.45 indicates absence of cirrhosis (with a negative predictive value of 90% for advanced fibrosis); FIB 4 between 1.45 - 3.25 are deemed inconclusive; FIB 4 >3.25 indicates cirrhosis (with a positive predictive value of 65% for advanced fibrosis).
Measured: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 24
FIB4 Score Values Over Time: Cohort 2
The FIB 4 score evaluates the degree of fibrosis in patients suspected of or already diagnosed with hepatic fibrosis. FIB-4 is calculated as (Age (years) * aspartate aminotransferase) / (platelets * √(ALT)).
The result provided from the above equation is interpreted according to 2 cut off values: FIB 4 <1.45 indicates absence of cirrhosis (with a negative predictive value of 90% for advanced fibrosis); FIB 4 between 1.45 - 3.25 are deemed inconclusive; FIB 4 >3.25 indicates cirrhosis (with a positive predictive value of 65% for advanced fibrosis).
Measured: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 22, Week 28, Week 28 + 1 day, Week 34, Week 40, Week 48
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
The APRI suggests the level of hepatic fibrosis and possible liver disease. APRI is calculated as 100*(aspartate aminotransferase/40) / platelets. Scores indicate the following: < 0.5 = fibrosis is ruled out; 0.5 - 0.7 = associated with some kind of liver damage; 0.7 - 1 = significant fibrosis; > 1 = associated with cirrhosis.
Measured: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 24
APRI Values Over Time: Cohort 2
The APRI suggests the level of hepatic fibrosis and possible liver disease. APRI is calculated as 100*(aspartate aminotransferase/40) / platelets. Scores indicate the following: < 0.5 = fibrosis is ruled out; 0.5 - 0.7 = associated with some kind of liver damage; 0.7 - 1 = significant fibrosis; > 1 = associated with cirrhosis.
Measured: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 22, Week 28, Week 34, Week 40, Week 48
N-Terminal Type III Collagen Propeptide (PRO-C3) Values Over Time: Cohorts 1/1b
PRO-C3 may be a biomarker for the formation of fibrotic tissue in the liver. For serum, the normal range is 6.1 - 13.8 ng/mL (based on a study of human serum samples from healthy men and women). Due to ethnic, dietary and age variations, the reference limits given may not apply to all populations. A reduction in Pro-C3 over time may indicate a reduction in hepatic fibrogenesis.
Measured: Baseline, Weeks 4, 16, 24
PRO-C3 Values Over Time: Cohort 2
PRO-C3 may be a biomarker for the formation of fibrotic tissue in the liver. For serum, the normal range is 6.1 - 13.8 ng/mL (based on a study of human serum samples from healthy men and women). Due to ethnic, dietary and age variations, the reference limits given may not apply to all populations. A reduction in Pro-C3 over time may indicate a reduction in hepatic fibrogenesis.
Measured: Baseline, Weeks 4, 16, 28, 40, 48
FibroScan® Values Over Time: Cohorts 1/1b
FibroScan is a type of liver elastography. Normal results are usually between 2 and 7 kilopascals (kPa), with results higher than the normal range if liver disease is present. The highest possible result is 75 kPa.
Measured: Baseline, Week 24
FibroScan® Values Over Time: Cohort 2
FibroScan is a type of liver elastography. Normal results are usually between 2 and 7 kilopascals (kPa), with results higher than the normal range if liver disease is present. The highest possible result is 75 kPa.
Measured: Baseline, Week 24
Portal Inflammation Over Time: Cohorts 1/1b
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of portal inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 24
Portal Inflammation Over Time: Cohort 2
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of portal inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 48
Interface Hepatitis Over Time: Cohorts 1/1b
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of interface hepatitis, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 24
Interface Hepatitis Over Time: Cohort 2
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of interface hepatitis, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 48
Lobular Inflammation Over Time: Cohorts 1/1b
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of lobular inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 24
Lobular Inflammation Over Time: Cohort 2
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of lobular inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 48
Hepatocyte Cell Death Over Time: Cohorts 1/1b
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1- point worsening from the baseline category in the liver biopsy parameter of hepatocyte cell death. Hepatocyte Cell Death Score: 0 = No acidophil bodies; 1 = Few acidophil bodies; 2 = Many acidophil. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 24
Hepatocyte Cell Death Over Time: Cohort 2
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of hepatocyte cell death. Hepatocyte Cell Death Score: 0 = No acidophil bodies; 1 = Few acidophil bodies; 2 = Many acidophil. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Measured: Baseline, Week 48
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohorts 1/1b
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1- point worsening from the baseline category in the METAVIR fibrosis stage score. The METAVIR scoring system is a system used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C. The stage represents the amount of fibrosis or scarring. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
F0: no fibrosis F1: portal fibrosis without septa F2: portal fibrosis with few septa F3: numerous septa without cirrhosis F4: cirrhosis
Measured: Baseline, Week 24
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohort 2
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1- point worsening from the baseline category in the METAVIR fibrosis stage score. The METAVIR scoring system is a system used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C. The stage represents the amount of fibrosis or scarring. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
F0: no fibrosis F1: portal fibrosis without septa F2: portal fibrosis with few septa F3: numerous septa without cirrhosis F4: cirrhosis
Measured: Baseline, Week 48
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An Adverse Event (AE) is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. Serious Adverse Event (SAE) is an AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is a medically important event or reaction. TEAEs are AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. Not related events include those reported as 'Not Related' to study drug. Related events include those reported as 'Possibly Related' or 'Probably Related' to study drug.
Measured: From first dose of study drug up to a maximum duration of study follow-up of 202 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Oct 201914 Dec 2023

First posted10 May 2019
Study start31 Oct 2019
Primary completion28 Apr 2022
Study completion14 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Alpha 1-Antitrypsin DeficiencyStudies of the same condition, open and under way.
More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03946449
Sponsor's protocol ID: AROAAT2002
Other IDs: 2019-000068-86, 2019
Status last verified: Oct 2025
First submitted: 8 May 2019
Last updated: 15 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 35748699

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Alpha 1 Antitrypsin Deficiency

All Alpha 1-Antitrypsin Deficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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)
ClinicalTrials.gov ID: NCT03946449
Acronym / sponsor ID: AROAAT2002
Conditions: Alpha 1-Antitrypsin Deficiency
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Arrowhead PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 31 Oct 2019 (actual)
Primary completion: 28 Apr 2022 (actual)
Study completion: 14 Dec 2023 (actual)
First posted: 10 May 2019 (actual)
Results: Posted 20 Apr 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
ARO-AAT 100 mg Cohort 1b	Experimental	Drug: ARO-AATPrimary 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.
ARO-AAT 200 mg Cohort 1	Experimental	Drug: ARO-AATPrimary 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.
ARO-AAT 200 mg Cohort 2	Experimental	Drug: ARO-AATPrimary 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ARO-AATAlso: Fazirsiran Injection, TAK-999solution for subcutaneous injection	Drug	ARO-AAT 100 mg Cohort 1b, ARO-AAT 200 mg Cohort 1, ARO-AAT 200 mg Cohort 2

Primary outcome

Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b
Time frame: 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
Time frame: Baseline, Week 48

25 secondary outcomes

Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b
Time frame: Baseline, Weeks 2, 4, 6, 16, 24
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Time frame: Baseline, Weeks 2, 4, 6, 16, 22, 28, 34, 40, 48
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Time frame: 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
Time frame: 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
Time frame: 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
GGT Values Over Time: Cohort 2
Time frame: 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
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Time frame: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 24
FIB4 Score Values Over Time: Cohort 2
Time frame: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 22, Week 28, Week 28 + 1 day, Week 34, Week 40, Week 48
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Time frame: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 24
APRI Values Over Time: Cohort 2
Time frame: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 22, Week 28, Week 34, Week 40, Week 48
N-Terminal Type III Collagen Propeptide (PRO-C3) Values Over Time: Cohorts 1/1b
Time frame: Baseline, Weeks 4, 16, 24
PRO-C3 Values Over Time: Cohort 2
Time frame: Baseline, Weeks 4, 16, 28, 40, 48
FibroScan® Values Over Time: Cohorts 1/1b
Time frame: Baseline, Week 24
FibroScan® Values Over Time: Cohort 2
Time frame: Baseline, Week 24
Portal Inflammation Over Time: Cohorts 1/1b
Time frame: Baseline, Week 24
Portal Inflammation Over Time: Cohort 2
Time frame: Baseline, Week 48
Interface Hepatitis Over Time: Cohorts 1/1b
Time frame: Baseline, Week 24
Interface Hepatitis Over Time: Cohort 2
Time frame: Baseline, Week 48
Lobular Inflammation Over Time: Cohorts 1/1b
Time frame: Baseline, Week 24
Lobular Inflammation Over Time: Cohort 2
Time frame: Baseline, Week 48
Hepatocyte Cell Death Over Time: Cohorts 1/1b
Time frame: Baseline, Week 24
Hepatocyte Cell Death Over Time: Cohort 2
Time frame: Baseline, Week 48
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohorts 1/1b
Time frame: Baseline, Week 24
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohort 2
Time frame: Baseline, Week 48
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to a maximum duration of study follow-up of 202 weeks.

Results and safety

Results posted to the registry on 20 Apr 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ARO-AAT 100 mg Cohort 1b	4	4
ARO-AAT 200 mg Cohort 1	4	4
ARO-AAT 200 mg Cohort 2	8	8

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

Time frame: Baseline, Week 24. Mean (Standard Deviation). Unit: percent change

Measure	ARO-AAT 100 mg Cohort 1b n = 4	ARO-AAT 200 mg Cohort 1 n = 4
Total Liver Z-AAT	-83.07 (5.830)	-79.84 (10.519)
Insoluble Liver-ZAAT	-81.58 (6.947)	-12.91 (131.702)
Soluble Liver Z-AAT	-85.36 (4.835)	-88.18 (5.718)

Population analysed: Full Analysis Set: all participants who received at least one dose of study drug and had baseline and post-dose liver biopsy histology results available.

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

Time frame: Baseline, Week 48. Mean (Standard Deviation). Unit: percent change

Measure	ARO-AAT 200 mg Cohort 2 n = 7
Total Liver Z-AAT	-90.26 (9.029)
Insoluble Liver-ZAAT	-84.83 (19.920)
Soluble Liver Z-AAT	-92.64 (7.482)

Population analysed: Full Analysis Set: all participants who received at least one dose of study drug and had baseline and post-dose liver biopsy histology results available. Participants with an assessment at given time point.

25 secondary outcomes are reported in the full results.

Adverse events

Time frame: For a maximum duration of study follow-up of 202 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ARO-AAT 100 mg Cohort 1b	0 of 4 (0%)	4 of 4 (100%)	0 of 4
ARO-AAT 200 mg Cohort 1	4 of 4 (100%)	4 of 4 (100%)	0 of 4
ARO-AAT 200 mg Cohort 2	5 of 8 (62.5%)	8 of 8 (100%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35748699Strnad 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

4 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ARO-AAT in people with Alpha 1-Antitrypsin Deficiency, run by Arrowhead Pharmaceuticals at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United Kingdom, Austria, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b (time frame: Baseline, Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03946449, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2025.