Study to Check the Safety of Fazirsiran and Learn if Fazirsiran Can Help People With Liver Disease and Scarring (Fibrosis) Due to an Abnormal Version of Alpha-1 Antitrypsin Protein

Recruiting now · Phase 3 · Has a placebo group

Conditions studied: Alpha1-Antitrypsin Deficiency

In brief

The main aim of this study is to learn if fazirsiran reduces liver scarring (fibrosis) compared to placebo. Other aims are to learn if fazirsiran slows down the disease worsening in the liver, to get information on how fazirsiran affects the body (called pharmacodynamics), to learn if fazirsiran reduces other liver injury (inflammation) and the abnormal Z-AAT protein in the liver, to get information on how the body processes fazirsiran (called pharmacokinetics), to test how well fazirsiran works compared with a placebo in improving measures of liver scarring including imaging and liver biomarkers (substances in the blood that the body normally makes and help show if liver function is improving, staying the same, or getting worse) as well as to check for side effects in participants treated with fazirsiran compared with those who received placebo. Participants will either receive fazirsiran or placebo. Liver biopsies, a way of collecting a small tissue sample from the liver, will be taken twice during this study.

Key facts

Study ID

NCT05677971

Run by

Takeda

People needed

160

Starts

2023-03-06

Expected to finish

2031-12-12

Last updated by the study team

2026-05-13

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The participant must have a diagnosis of the Z allele homozygotes (PiZZ) genotype AATD. PiZZ diagnosis from source verifiable medical records is permitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not permitted.
• The participant, of any sex, is aged 18 to 75 years, inclusive.
• The participant's liver biopsy core sample collected should meet the requirements of the protocol.
• The participant has evidence of METAVIR stage F2, F3, or F4 liver fibrosis, evaluated by a centrally read baseline liver biopsy during the screening period; or confirmed as meeting all the entry criteria by central reading of a previous biopsy conducted within 6 months before the estimated enrollment date using an adequate liver biopsy and slides as defined in the study laboratory manual.
• The participant has a pulmonary status meeting the protocol's requirements.
• It must be confirmed that the participant does not have HCC. Participants will be screened for HCC with alpha-fetoprotein (AFP) and abdominal ultrasound. If the participant has any of the following, they will be required to have contrast-enhanced CT or MRI imaging to exclude HCC before randomization.
• An adult participant must have a body mass index (BMI) greater than or equal to (>=) 18.0 kilograms per meter square (kg\^m2).
• The participant is a nonsmoker for at least 6 months before screening.

You may not qualify if…

• The participant has a history of liver decompensating events (overt hepatic encephalopathy [West Haven Grade >=2] documented by a physician or healthcare professional, clinically significant ascites, spontaneous bacterial peritonitis, GI bleeding from varices, hepatopulmonary syndrome, hepatorenal syndrome, portal pulmonary hypertension, or bleeding portal hypertensive gastropathy).
• The participant has a history of the presence of medium or large varices or varices with red wale signs based on a previous esophagogastroduodenoscopy (EGD) within 6 months before the estimated enrollment date. For certain participants, an EGD will be required at screening if there is no EGD available within 6 months before the estimated enrollment date. Presence of small varices with no red wale signs on EGD and no history of bleeding will be acceptable for study eligibility.
• The participant has evidence of chronic liver disease attributable to other diseases, including viral hepatitis B or C, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary diversion, or autoimmune hepatitis.
• The participant has alanine transaminase (ALT) or aspartate transaminase (AST) levels >250 units per liter (U/L).
• The participant has a platelet count <60,000 per cubic millimeter (mm\^3) (<60 × 10\^9 per liter [10\^9/L]).
• The participant has albumin <=2.8 gram per deciliter (g/dL) (28 grams per liter [g/L]).
• The participant has international normalized ratio (INR) >=1.7.
• The participant is expected to have severe and unavoidable high-level exposure to inhaled pulmonary toxins during the study such as may occur with occupational exposure to mineral dusts or metals.
• The participant has a history of drug abuse (such as cocaine, phencyclidine) within 1 year before the screening visit or has a positive urine drug screen at screening.
• The participant has previously been treated with fazirsiran or any other RNAi for AATD-LD.
• The participant has portal vein thrombosis.
• The participant has a prior transjugular portosystemic shunt procedure.
• The participant has a history of malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with other curatively treated malignancies who have no evidence of metastatic disease and a greater than 1-year disease-free interval may be entered after approval by the medical monitor.

Where it is running

• Columbia University Irving Medical Center — New York, New York, United States (enrolling)
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (enrolling)
• St. Joseph's Hospital and Medical Center — Phoenix, Arizona, United States (enrolling)
• University of Alabama at Birmingham — Birmingham, Alabama, United States (enrolling)
• Mayo Clinic — Phoenix, Arizona, United States (enrolling)
• UCLA Pulmonary and Critical Care — Los Angeles, California, United States (enrolling)
• Stanford University — Palo Alto, California, United States (enrolling)
• University of California Benioff Children's Hospital — San Francisco, California, United States (enrolling)
• Peak Gastroenterology Associates, PC — Colorado Springs, Colorado, United States (enrolling)
• University of Florida — Gainesville, Florida, United States (enrolling)
• Schiff Center for Liver Diseases/University of Miami — Miami, Florida, United States (enrolling)
• University of California San Diego, Altman Clinical and Translational Institute — La Jolla, California, United States (enrolling)
• Indiana University School of Medicine - Indianapolis — Indianapolis, Indiana, United States (enrolling)
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States (enrolling)
• Ochsner Medical Center — New Orleans, Louisiana, United States (enrolling)
• University of Maryland Medical Center — Baltimore, Maryland, United States (enrolling)
• Brigham and Womens Hospital — Boston, Massachusetts, United States (enrolling)
• Boston Medical Center — Boston, Massachusetts, United States (enrolling)
• University of Michigan Hospital — Ann Arbor, Michigan, United States (enrolling)
• Henry Ford Medical Center - Columbus — Novi, Michigan, United States (enrolling)
• Mayo Clinic - PPDS — Rochester, Minnesota, United States (enrolling)
• Cardinal Glennon Children's Hospital — St Louis, Missouri, United States (enrolling)
• Washington University School of Medicine in St. Louis — St Louis, Missouri, United States (enrolling)
• NYU Langone Health — New York, New York, United States (enrolling)
• Penn State Health Milton S. Hershey Medical Center — Hershey, Pennsylvania, United States (enrolling)

Full record on ClinicalTrials.gov

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