- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03946449
Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Vienna, Austria, 1090
- Medical University of Vienna Division of Gastroenterology and Hepatology
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Aachen, Germany, 52074
- Universitatsklinikum Aachen, Anstalt des offentlich
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Cambridge, United Kingdom, CB2 0QQ
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust
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Edinburgh, United Kingdom, EH19 3BJ
- Royal Infirmary of Edinburgh, NHS Lothian
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Fazirsiran (TAK-999, ARO-AAT) Cohort 1
Administered on Day 1, Weeks 4 and 16 for a minimum of 3 doses. Treatment Extension (optional enrollment): Administered every 12 weeks for 12 additional doses. |
solution for subcutaneous (sc) injection
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Experimental: Fazirsiran (TAK-999, ARO-AAT) Cohort 1b
Administered on Day 1, Weeks 4 and 16, for a minimum of 3 doses. Treatment Extension (optional enrollment): Administered every 12 weeks for 12 additional doses. |
solution for subcutaneous (sc) injection
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Experimental: Fazirsiran (TAK-999, ARO-AAT) Cohort 2
Administered on Day 1, Weeks 4, 16, 28 and 40 for a minimum of 5 doses. Treatment Extension (optional enrollment): Administered every 12 weeks for 12 additional doses. |
solution for subcutaneous (sc) injection
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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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
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Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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Baseline through Week 24 (Cohort 1 & 1b) or through Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140
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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
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Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140
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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
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Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Weeks 44 and 140
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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
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Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140
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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
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Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140
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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
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Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 140
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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
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Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Weeks 44 and 140
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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
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Change in inflammation score, based on pathology slide reads.
Inflammation was assessed on a scale of 0-3, with higher scores showing more severe inflammation.
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Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44
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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
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Change in steatosis score, based on pathology slide reads.
Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis.
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Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44
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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
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Change in hepatocyte cell death score, based on pathology slide reads.
Hepatocyte cell death was assessed on a scale of 0-2, with higher scores showing more severe hepatocyte cell death.
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Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44
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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
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METAVIR scores range from F0 to F4 (F0=No Fibrosis, F1=Mild Fibrosis, F2= Significant Fibrosis, F3=Severe Fibrosis, F4=Cirrhosis).
Higher scores indicate more severe fibrosis.
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Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44
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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
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Up to Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: up to Extension Week 140
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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
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Day 1, Week 6, and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Weeks 24 and 44
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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
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Day 1, Week 6, and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Weeks 24 and 44
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AROAAT2002
- 2019-000068-86 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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