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Clinical Trials in Ireland / NCT05677971
Recruiting Phase 3

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

NCT05677971 · tracked via the Priya Life Science Ireland tracker
Sponsor
Takeda
Phase
Phase 3
Started
2023-03-06
Last updated
2026-05-13

Condition(s) studied

Alpha1-Antitrypsin Deficiency

Investigational drug(s) / intervention(s)

Fazirsiran InjectionPlacebo

Fazirsiran Injection: Participants will receive fazirsiran 200 mg/ml SC injection on Day 1, at Week 4, and Q12 W thereafter up to Week 196.

Placebo: Participants will receive placebo (sterile normal saline \[0.9% NaCl\]) SC injection on Day 1, at Week 4, and Q12 W thereafter up to Week 196.

Study summary

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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion criteria: * 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. Exclusion Criteria * 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.

Primary outcome measure(s)

Trial sites (89)

FacilityCityRegionStatus
University of Alabama at Birmingham Birmingham Alabama Recruiting
St. Joseph's Hospital and Medical Center Phoenix Arizona Recruiting
Mayo Clinic Phoenix Arizona Recruiting
University of Arizona Thomas D. Boyer Liver Institute Tucson Arizona Withdrawn
Gastroenterology & Liver Institute Escondido California Withdrawn
University of California San Diego, Altman Clinical and Translational Institute La Jolla California Recruiting
UCLA Pulmonary and Critical Care Los Angeles California Recruiting
Stanford University Palo Alto California Recruiting
University of California Benioff Children's Hospital San Francisco California Recruiting
Peak Gastroenterology Associates, PC Colorado Springs Colorado Recruiting
University of Florida Gainesville Florida Recruiting
Schiff Center for Liver Diseases/University of Miami Miami Florida Recruiting
Children's Healthcare of Atlanta Atlanta Georgia Withdrawn
Indiana University School of Medicine - Indianapolis Indianapolis Indiana Recruiting
University of Iowa Hospitals and Clinics Iowa City Iowa Recruiting
Ochsner Medical Center New Orleans Louisiana Recruiting
University of Maryland Medical Center Baltimore Maryland Recruiting
Brigham and Womens Hospital Boston Massachusetts Recruiting
Boston Medical Center Boston Massachusetts Recruiting
University of Michigan Hospital Ann Arbor Michigan Recruiting
Henry Ford Medical Center - Columbus Novi Michigan Recruiting
Mayo Clinic - PPDS Rochester Minnesota Recruiting
Cardinal Glennon Children's Hospital St Louis Missouri Recruiting
Washington University School of Medicine in St. Louis St Louis Missouri Recruiting
NYU Langone Health New York New York Recruiting
Morgan Stanley Childrens Hospital of New York Presbyterian (CHONY) - PIN New York New York Withdrawn
Columbia University Irving Medical Center New York New York Recruiting
University Hospitals Cleveland Medical Center Cleveland Ohio Recruiting
Penn State Health Milton S. Hershey Medical Center Hershey Pennsylvania Recruiting
Temple University Hospital Philadelphia Pennsylvania Recruiting
Medical University of South Carolina Charleston South Carolina Recruiting
Vanderbilt University Medical Center Nashville Tennessee Recruiting
Texoma Liver Center Denison Texas Recruiting
Baylor College of Medicine Medical Center Houston Texas Recruiting
The Texas Liver Institute San Antonio Texas Recruiting
Bon Secours St. Mary's Hospital Richmond Virginia Recruiting
VCU Medical Center North Hospital Richmond Virginia Recruiting
Royal Adelaide Hospital Adelaide South Australia Withdrawn
St Vincents Hospital Melbourne - PPDS Fitzroy Victoria Recruiting
LKH-Universitätsklinikum Graz Graz Austria Recruiting

+ 49 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05677971 on ClinicalTrials.gov ↗ ← All trials in Ireland