A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Fazirsiran in the Treatment of Alpha-1 Antitrypsin Deficiency–Associated Liver Disease With METAVIR Stage F2 to F4 Fibrosis

Alpha-1 Antitrypsin Deficiency-Associated Liver Disease

The primary endpoint of this study is decrease from baseline of at least stage of histologic fibrosis (Meta-Analysis of Histological Data in Viral Hepatitis [METAVIR] staging) in the centrally read liver biopsy done at Week 106 in AATD-LD with METAVIR stage F2 and F3 fibrosis (Yes/No).

1. Percent change from baseline in intrahepatic Z-AAT protein at Week 106 in AATD-LD with METAVIR stage F2 to F3 fibrosis., 2. Decrease from baseline of at least 1 stage of histologic fibrosis (METAVIR staging) in the centrally read liver biopsy done at Week 202 in AATD-LD with METAVIR stage F2 to F4 fibrosis (Yes/No), 3. Disease progression, which is defined as progression to cirrhosis or any of the qualifying liver-related clinical events by Week 202 in AATD-LD with METAVIR stage F2 to F4 fibrosis, including the occurrence of 1 or more of the following aggregated liver related clinical events during this period (Yes/No), 4. Change from baseline in serum Z-AAT protein at Week 202 in AATD-LD with METAVIR stage F2 to F4 fibrosi, 5. Change from baseline in intrahepatic Z-AAT protein polymer burden assessed by periodic acid Schiff plus diastase (PAS+D) staining in Week 202 liver biopsy in AATD-LD with METAVIR stage F2 to F4 fibros, 6. Change from baseline in intrahepatic portal inflammation in Week 202 liver biopsy in AATD-LD with METAVIR stage F2 to F4 fibrosis., 7. Change from baseline in vibration-controlled transient elastography (VCTE)-derived liver stiffness at Week 202 in AATD-LD with METAVIR stage F2 to F4 fibrosis., The secondary PK endpoints are: 1. Observed plasma concentrations of fazirsiran on Day 1 (predose, 2, 4, and 6 hours postdose), and predose and 2 hours postdose at Weeks 4, 16, 28, 40, 52, 76, 100, 124, 148, 172 and 196 and anytime at Weeks 106, 202, and safety follow-up.

No related papers found yet.

Austria, Belgium, Czechia, Denmark, France, Germany, Ireland, Italy, Netherlands, Poland, Portugal, Spain, Sweden