Phase 2
N=40
Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT)
Alpha 1-Antitrypsin Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT03945292 ↗Enrolled (actual)
40
Serious AEs
14.3%
Results posted
Dec 2024
Primary outcome: Primary: Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 — -62.17; -85.39; -92.93; 4.64 percentage change — p=< 0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Fazisiran Injection (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Arrowhead Pharmaceuticals
- Primary completion
- Nov 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 |
-62.17; -85.39; -92.93; 4.64 | < 0.0001 sig |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase |
9; 8; 9; 14; 0; 0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase |
4; 4; 3; 9; 1; 1 | — |
| SECONDARY Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis |
-89.341; -259.892; -29.371; -4.738 | — |
| SECONDARY Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis |
-86.89; -81.61; -98.16; 42.42 | 0.0021 sig |
| SECONDARY Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis |
-20.427; -109.747; -17.418; 2.300 | — |
| SECONDARY Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis |
-75.73; -87.23; -95.71; 22.33 | 0.0001 sig |
| SECONDARY Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis |
-68.914; -150.145; -11.953; -7.038 | — |
| SECONDARY Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis |
-86.36; -72.44; -101.85; 91.35 | 0.0247 sig |
| SECONDARY Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS) |
-3.0; -2.4; -8.4; 1.7; -7.3; -3.8 | — |
| SECONDARY Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS |
-9.6; -4.3; -15.3; 5.8; -15.7; -9.7 | — |
| SECONDARY Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS |
-2.9; -0.1; 1.1; 0.7; -7.7; 0.0 | — |
| SECONDARY Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS |
-8.3; 2.6; 3.5; 2.5; -16.9; 0.4 | — |
| SECONDARY Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS |
-2.8; -4.3; -13.8; 4.9; -9.7; -1.0 | — |
| SECONDARY Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS |
-0.5; -5.6; -17.7; 5.8; -8.9; -1.2 | — |
| SECONDARY Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS |
2.8; -4.3; -9.1; 7.0; -3.7; -4.8 | — |
| SECONDARY Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS |
5.9; -9.7; -14.8; 13.9; 0.8; -9.1 | — |
| SECONDARY Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS |
0.079; 0.098; -0.051; -0.004; 0.060; 0.163 | — |
| SECONDARY Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS |
19.2; 15.6; 3.4; 1.0; 16.4; 25.3 | — |
| SECONDARY Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS |
0.016; -0.006; 0.005; 0.010; 0.013; 0.055 | — |
| SECONDARY Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS |
5.9; 1.5; 29.1; 15.1; 11.0; 22.4 | — |
| SECONDARY Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS |
-0.012; -0.006; 0.011; 0.055; 0.047; -0.085 | — |
| SECONDARY Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS |
-1.0; -0.7; 1.2; 2.6; 4.4; -7.0 | — |
| SECONDARY Absolute Change in Serum Z-AAT Over Time Through EOS |
-125.511; -156.714; -169.044; 16.929; -146.267; -178.413 | — |
| SECONDARY Percent Change in Serum Z-AAT Over Time Through EOS |
-50.8; -69.9; -85.5; 10.0; -60.0; -82.2 | — |
| SECONDARY Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran |
0; 2; 2; 0; 1; 2 | — |
| SECONDARY Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis |
66.7; 40.0; 50.0; 37.5; 25.0; 60.0 | — |
Summary
The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, efficacy and tolerability of multiple doses of the investigational product, Fazirsiran Injection, administered subcutaneously to participants with alpha-1 antitrypsin deficiency (AATD).
Eligibility Criteria
Inclusion Criteria
- Diagnosis of AATD
- Liver biopsy at Screening indicating liver fibrosis (score less than F4); a patient with no fibrosis may participate based on a previous biopsy conducted within one year
- Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, 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
- Previous lung or liver transplant due to AATD
- 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 (NCT03945292). 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.