The main aim of this study is to learn if fazirsiran is safe during long-term use in people with liver disease caused by the abnormal Z-alpha-1 antitrypsin (Z-AAT) protein. People who have taken part in previous fazirsiran studies (AROAAT2001 \[NCT03945292\] or AROAAT2002 \[NCT03946449\]) can continue to receive fazirsiran every 3 months as long as they participate in this study, the study is ongoing or until health authorities in their country approve fazirsiran to be publicly available. The study may also provide information on whether fazirsiran has a long-term effect in reducing liver fibrosis or slowing down the progression of liver fibrosis in people with liver disease due to the abnormal Z-AAT protein.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Fazirsiran will be injected subcutaneously.
UCSD Altman Clinical and Translational Research Institute
La Jolla, California, United States
Stanford Medicine Outpatient Center
Redwood City, California, United States
UF Clinical and Translational Science Institute
Gainesville, Florida, United States
University Of Iowa Hospitals And Clinics
Iowa City, Iowa, United States
Medical University of South Carolina - Hollings Cancer Center - PPDS
Charleston, South Carolina, United States
Medizinische Universitat Wien (Medical University of Vienna)
Vienna, Austria
Universitätsklinikum der RWTH Aachen
Aachen, North Rhine-Westphalia, Germany
Hospital Nélio Mendonça
Funchal, Portugal
Addenbrooke's Hospital
Cambridge, United Kingdom
Royal Infirmary of Edinburgh - PPDS
Edinburgh, United Kingdom
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not it is considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study intervention. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, suspected transmission of any infectious agent, an important medical event. AEs and SAEs including any pulmonary AEs or SAEs indicative of worsening pulmonary condition (example, pulmonary exacerbation, respiratory infection, significant pulmonary function test decline) will be reported.
Time frame: From start of study drug administration (in current study) up to End of study (EOS) (current study [up to 10 years])
Number of Participants With Clinically Significant Changes From Baseline in Pulmonary Function Parameters
Standard pulmonary function parameters measured will be used to study lung function. Clinical significance of pulmonary function parameters will be determined at the investigator's discretion.
Time frame: Baseline (current study), up to EOS (current study up to 10 years])
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs include body temperature, respiratory rate, sitting blood pressure (systolic and diastolic, resting more than 5 minutes), pulse, oxygen saturation. Clinical significance of vital signs will be determined at the investigator's discretion.
Time frame: From start of study drug administration (in current study) up to EOS (current study [up to 10 years])
Number of Participants With Clinically Significant Changes in Laboratory Parameters
Laboratory parameters include hematology, biochemistry including liver tests, coagulation, and urinalysis. Clinical significance of laboratory parameters will be determined at the investigator's discretion.
Time frame: From start of study drug administration (in current study) up to EOS (current study [up to 10 years])
Number of Participants With no Progression from Baseline of At least 1 Stage of Histologic Fibrosis on Liver Biopsy at Week 102
Number of participants with no progression from baseline of at least 1 stage of histologic fibrosis (by Meta-Analysis of Histological Data in Viral Hepatitis \[METAVIR\] staging) on liver biopsy at Week 102 will be reported.
Time frame: At Week 102 (current study)
Number of Participants With Reduction from Baseline of At least 1 Stage of Histologic Fibrosis on Liver Biopsy at Week 102
Number of participants with baseline fibrosis of F1 or higher, a decrease from baseline of at least 1 stage of histologic fibrosis (by METAVIR staging) on liver biopsy at Week 102 will be reported.
Time frame: At Week 102 (current study)
Change from Baseline in Intrahepatic Z-AAT Protein Polymer Burden Assessed by Periodic Acid Schiff Plus Diastase (PAS+D) Staining in Liver Biopsy at Week 102
Change from baseline in intrahepatic Z-AAT protein polymer burden assessed by PAS+D staining in liver biopsy will be assessed.
Time frame: Baseline (current study), Week 102 (current study)
Change from Baseline in Intrahepatic Portal Inflammation Score at Week 102 in Liver Biopsy
Change in portal inflammation score in liver biopsy, based on pathology slide reads. Inflammation will be assessed on a scale of 0-3, with higher scores showing more severe inflammation.
Time frame: Baseline (current study), Week 102 (current study)
Change from Baseline in Liver Stiffness Assessed by Magnetic Resonance Elastography (MRE)
Change from baseline in MRE-derived liver stiffness will be assessed.
Time frame: Baseline (current study), up to EOS (current study up to 10 years])
Change from Baseline in Liver Stiffness Assessed by Vibration-Controlled Transient Elastography (VCTE)
Change from baseline in VCTE-derived liver stiffness will be assessed.
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Time frame: Baseline (current study), up to EOS (current study up to 10 years])