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RECRUITING

NCT05677971

PHASE3

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

Sponsor: Takeda

View on ClinicalTrials.gov

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.

Official title: 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

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

160

Start Date

2023-03-06

Completion Date

2030-08-14

Last Updated

2026-03-05

Healthy Volunteers

Conditions

Alpha1-Antitrypsin Deficiency

Interventions

DRUG

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.

OTHER

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.

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) between 18.0 and 39.0 kilograms per meter square (kg\^m2), inclusive. * 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, 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 other forms of chronic liver 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 deciliter \[g/L\]). * 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.

Locations (89)

University of Alabama at Birmingham

Birmingham, Alabama, United States

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Mayo Clinic

Phoenix, Arizona, United States

University of Arizona Thomas D. Boyer Liver Institute

Tucson, Arizona, United States

Gastroenterology & Liver Institute

Escondido, California, United States

University of California San Diego, Altman Clinical and Translational Institute

La Jolla, California, United States

UCLA Pulmonary and Critical Care

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

University of California Benioff Children's Hospital

San Francisco, California, United States

Peak Gastroenterology Associates, PC

Colorado Springs, Colorado, United States

University of Florida

Gainesville, Florida, United States

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Indiana University School of Medicine - Indianapolis

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

University of Michigan Hospital

Ann Arbor, Michigan, United States

Henry Ford Medical Center - Columbus

Novi, Michigan, United States

Mayo Clinic - PPDS

Rochester, Minnesota, United States

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

NYU Langone Health

New York, New York, United States

Morgan Stanley Childrens Hospital of New York Presbyterian (CHONY) - PIN

New York, New York, United States

Columbia University Irving Medical Center

New York, New York, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texoma Liver Center

Denison, Texas, United States

Baylor College of Medicine Medical Center

Houston, Texas, United States

The Texas Liver Institute

San Antonio, Texas, United States

Bon Secours St. Mary's Hospital

Richmond, Virginia, United States

VCU Medical Center North Hospital

Richmond, Virginia, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

St Vincents Hospital Melbourne - PPDS

Fitzroy, Victoria, Australia

LKH-Universitätsklinikum Graz

Graz, Austria

Medizinische Universität Innsbruck

Innsbruck, Austria

Klinikum Klagenfurt Am Wörthersee

Klagenfurt, Austria

Medizinische Universität Wien (Medical University of Vienna)

Vienna, Austria

UZ Antwerpen

Antwerp, Belgium

UZ Leuven

Leuven, Belgium

Hospital de Base do Distrito Federal

Brasília, Brazil

Hospital Sirio-Libanes

São Paulo, Brazil

Universidade Estadual Paulista Julio de Mesquita Filho Faculdade de Medicina Campus de Botucatu

São Paulo, Brazil

GI Research Institute

Vancouver, British Columbia, Canada

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, Canada

Inspiration Research Limited

Toronto, Ontario, Canada

Institut klinicke a experimentalni mediciny

Prague, Czechia

Hvidovre Hospital

Hvidovre, Denmark

Hôpital Beaujon

Clichy, France

Hôpital de La Croix Rousse

Lyon, France

Centre Francois Magendie

Pessac, France

Hopital PONTCHAILLOU CHU de Rennes

Rennes, France

Hospital Purpan

Toulouse, France

Hôpital Paul Brousse

Val-de-Marne, France

Universitätsklinikum der RWTH Aachen

Aachen, Germany

Charité - Campus Virchow-Klinikum-Ostring 1

Berlin, Germany

Hannover Medical School

Hanover, Germany

Universitätsklinikum Schleswig-Holstein - Campus Kiel

Kiel, Germany

Universitätsklinikum Tübingen

Tübingen, Germany

Beaumont Hospital

Dublin, Ireland

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Italy

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, Italy

IRCCS Istituto Clinico Humanitas

Rozzano, Italy

Amsterdam UMC - VUmc - De Boelelaan

Amsterdam, Netherlands

Leiden University Medical Center

Leiden, Netherlands

ID Clinic Arkadiusz Pisula

Śląskie, Poland

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, Poland

CCA Hospital Braga

Braga, Portugal

Hospital Nélio Mendonça

Funchal, Portugal

Centro Hospitalar do Porto

Porto, Portugal

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, Spain

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Hospital Universitario Marques de Valdecilla

Santander, Spain

Hospital Universitario Virgen del Rocio - PPDS

Seville, Spain

Karolinska Universitetssjukhuset Huddinge

Huddinge, Sweden

Universitetssjukhuset i Linköping

Linköping, Sweden

Inselspital Bern

Bern, Switzerland

Addenbrooke's Hospital

Cambridge, United Kingdom

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Royal Free Hospital

London, United Kingdom

King's College Hospital

London, United Kingdom

Queen's Medical Centre

Nottingham, United Kingdom

Derriford Hospital

Plymouth, United Kingdom

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (89)