Phase 2
N=16
Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)
Alpha 1-Antitrypsin Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT03946449 ↗Enrolled (actual)
16
Serious AEs
56.3%
Results posted
Apr 2025
Primary outcome: Primary: Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b — -83.07; -79.84; -81.58; -12.91 percent change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ARO-AAT (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Arrowhead Pharmaceuticals
- Primary completion
- Apr 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b |
-83.07; -79.84; -81.58; -12.91; -85.36; -88.18 | — |
| PRIMARY Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 48: Cohort 2 |
-90.26; -84.83; -92.64 | — |
| SECONDARY Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b |
-69.12; -77.28; -80.24; -88.07; -87.27; -91.79 | — |
| SECONDARY Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2 |
-72.08; -82.22; -89.92; -85.76; -90.87; -85.06 | — |
| SECONDARY Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b |
58.5; 87.8; 58.5; 88.3; 76.5; 99.8 | — |
| SECONDARY ALT Values Over Time: Cohort 2 |
62.1; 58.6; 61.9; 55.3; 53.0; 54.9 | — |
| SECONDARY Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b |
70.8; 244.8; 70.5; 247.3; 66.0; 210.8 | — |
| SECONDARY GGT Values Over Time: Cohort 2 |
62.5; 62.1; 60.6; 59.1; 57.6; 58.0 | — |
| SECONDARY Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b |
1.425; 1.583; 1.353; 1.618; 1.580; 1.900 | — |
| SECONDARY FIB4 Score Values Over Time: Cohort 2 |
1.395; 1.543; 1.383; 1.420; 1.356; 1.367 | — |
| SECONDARY Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b |
0.485; 0.745; 0.463; 0.753; 0.633; 0.910 | — |
| SECONDARY APRI Values Over Time: Cohort 2 |
0.500; 0.515; 0.486; 0.479; 0.454; 0.463 | — |
| SECONDARY N-Terminal Type III Collagen Propeptide (PRO-C3) Values Over Time: Cohorts 1/1b |
16.78; 25.15; 16.90; 22.10; 15.60; 19.30 | — |
| SECONDARY PRO-C3 Values Over Time: Cohort 2 |
18.21; 15.81; 17.03; 14.31; 15.10; 17.09 | — |
| SECONDARY FibroScan® Values Over Time: Cohorts 1/1b |
7.28; 12.70; 7.30; 10.55 | — |
| SECONDARY FibroScan® Values Over Time: Cohort 2 |
9.89; 8.67 | — |
| SECONDARY Portal Inflammation Over Time: Cohorts 1/1b |
25.0; 50.0; 50.0; 50.0; 25.0; 0.0 | — |
| SECONDARY Portal Inflammation Over Time: Cohort 2 |
12.5; 37.5; 0.0; 50.0 | — |
| SECONDARY Interface Hepatitis Over Time: Cohorts 1/1b |
50.0; 0.0; 0.0; 100.0; 25.0; 0.0 | — |
| SECONDARY Interface Hepatitis Over Time: Cohort 2 |
25.0; 25.0; 0.0; 50.0 | — |
| SECONDARY Lobular Inflammation Over Time: Cohorts 1/1b |
0.0; 0.0; 25.0; 50.0; 50.0; 50.0 | — |
| SECONDARY Lobular Inflammation Over Time: Cohort 2 |
0.0; 62.5; 12.5; 25.0 | — |
| SECONDARY Hepatocyte Cell Death Over Time: Cohorts 1/1b |
0.0; 0.0; 25.0; 0.0; 25.0; 25.0 | — |
| SECONDARY Hepatocyte Cell Death Over Time: Cohort 2 |
0.0; 62.5; 0.0; 37.5 | — |
| SECONDARY Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohorts 1/1b |
0.0; 50.0; 100.0; 50.0; 0.0; 0.0 | — |
| SECONDARY Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohort 2 |
50.0; 12.5; 25.0; 12.5 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
4; 4; 8; 0; 3; 5 | — |
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).
Eligibility Criteria
Inclusion Criteria
- 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
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
Data sourced from ClinicalTrials.gov (NCT03946449). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.