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.

An Extension Study to Learn About the Long-Term Safety of Fazirsiran and if Fazirsiran Can Help People With Alpha-1 Antitrypsin Liver Disease

Alpha1-Antitrypsin Deficiency

Fazirsiran Injection

A Phase 3, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Fazirsiran in Participants With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease

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.

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.

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.

Laboratory parameters include hematology, biochemistry including liver tests,
coagulation, and urinalysis. Clinical significance of laboratory parameters will be
determined at the investigator's discretion.

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.

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.

Change from baseline in intrahepatic Z-AAT protein polymer burden assessed by PAS+D
staining in liver biopsy will be assessed.

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.

Change from baseline in MRE-derived liver stiffness will be assessed.

Change from baseline in VCTE-derived liver stiffness will be assessed.

Participants who are currently taking part in or who have completed their treatment in
parent studies AROAAT2001 (NCT03945292) and AROAAT2002 (NCT03946449) may rollover in this
study to receive fazirsiran, 200 milligrams (mg), injection, subcutaneously on Day 1 and
once every 12 weeks (Q12W) thereafter until fazirsiran receives approval and is
commercially available in the participant's country, until a participant withdraws from
the study or the sponsor decides to terminate the study.

An Extension Study to Learn About the Long-Term Safety of Fazirsiran and if Fazirsiran Can Help People With Alpha-1 Antitrypsin Liver Disease

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status