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

NCT ID: NCT05677971

Last Updated: 2025-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-06

Study Completion Date

2030-08-14

Brief Summary

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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.

Detailed Description

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Conditions

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Alpha1-Antitrypsin Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Fazirsiran

Participants will receive fazirsiran 200 milligram per milliliter (mg/ml) subcutaneous (SC) injection on Day 1, at Week 4, and then every 12 weeks (Q12 W) thereafter up to Week 196.

Group Type EXPERIMENTAL

Fazirsiran Injection

Intervention Type DRUG

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 on Day 1, at Week 4, and Q12 W thereafter up to Week 196.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type OTHER

Other Intervention Names

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TAK-999, ARO-AAT, ADS-001 Sodium chloride

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda Development Center Americas, Inc.

INDUSTRY

Sponsor Role collaborator

Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status RECRUITING

Mayo Clinic

Phoenix, Arizona, United States

Site Status RECRUITING

University of Arizona Thomas D. Boyer Liver Institute

Tucson, Arizona, United States

Site Status RECRUITING

Gastroenterology & Liver Institute

Escondido, California, United States

Site Status WITHDRAWN

University of California San Diego, Altman Clinical and Translational Institute

La Jolla, California, United States

Site Status RECRUITING

UCLA Pulmonary and Critical Care

Los Angeles, California, United States

Site Status RECRUITING

Stanford University

Palo Alto, California, United States

Site Status RECRUITING

University of California Benioff Children's Hospital

San Francisco, California, United States

Site Status RECRUITING

University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Site Status RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status WITHDRAWN

Indiana University School of Medicine - Indianapolis

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status RECRUITING

Brigham and Womens Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Boston Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan Hospital

Ann Arbor, Michigan, United States

Site Status RECRUITING

Henry Ford Medical Center - Columbus

Novi, Michigan, United States

Site Status RECRUITING

Mayo Clinic - PPDS

Rochester, Minnesota, United States

Site Status RECRUITING

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

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

New York, New York, United States

Site Status WITHDRAWN

Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Texoma Liver Center

Denison, Texas, United States

Site Status RECRUITING

Baylor College of Medicine Medical Center

Houston, Texas, United States

Site Status RECRUITING

The Texas Liver Institute

San Antonio, Texas, United States

Site Status RECRUITING

Bon Secours St. Mary's Hospital

Richmond, Virginia, United States

Site Status RECRUITING

VCU Medical Center North Hospital

Richmond, Virginia, United States

Site Status RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status WITHDRAWN

St Vincents Hospital Melbourne - PPDS

Fitzroy, Victoria, Australia

Site Status RECRUITING

LKH-Universitätsklinikum Graz

Graz, , Austria

Site Status RECRUITING

Medizinische Universität Innsbruck

Innsbruck, , Austria

Site Status RECRUITING

Klinikum Klagenfurt Am Wörthersee

Klagenfurt, , Austria

Site Status RECRUITING

Medizinische Universität Wien (Medical University of Vienna)

Vienna, , Austria

Site Status RECRUITING

UZ Antwerpen

Antwerp, , Belgium

Site Status RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status RECRUITING

Hospital Sirio-Libanes

São Paulo, , Brazil

Site Status RECRUITING

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

São Paulo, , Brazil

Site Status RECRUITING

GI Research Institute

Vancouver, British Columbia, Canada

Site Status RECRUITING

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, Canada

Site Status RECRUITING

Inspiration Research Limited

Toronto, Ontario, Canada

Site Status RECRUITING

Institut klinicke a experimentalni mediciny

Prague, , Czechia

Site Status RECRUITING

Hvidovre Hospital

Hvidovre, , Denmark

Site Status RECRUITING

Hôpital Beaujon

Clichy, , France

Site Status RECRUITING

Hôpital de La Croix Rousse

Lyon, , France

Site Status RECRUITING

Centre Francois Magendie

Pessac, , France

Site Status RECRUITING

Hopital PONTCHAILLOU CHU de Rennes

Rennes, , France

Site Status RECRUITING

Hospital Purpan

Toulouse, , France

Site Status RECRUITING

Hôpital Paul Brousse

Val-de-Marne, , France

Site Status RECRUITING

Universitätsklinikum der RWTH Aachen

Aachen, , Germany

Site Status RECRUITING

Charité - Campus Virchow-Klinikum-Ostring 1

Berlin, , Germany

Site Status RECRUITING

Hannover Medical School

Hanover, , Germany

Site Status RECRUITING

Universitätsklinikum Schleswig-Holstein - Campus Kiel

Kiel, , Germany

Site Status RECRUITING

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status RECRUITING

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status RECRUITING

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, , Italy

Site Status RECRUITING

IRCCS Istituto Clinico Humanitas

Rozzano, , Italy

Site Status RECRUITING

Amsterdam UMC - VUmc - De Boelelaan

Amsterdam, , Netherlands

Site Status RECRUITING

Leiden University Medical Center

Leiden, , Netherlands

Site Status RECRUITING

ID Clinic Arkadiusz Pisula

Śląskie, , Poland

Site Status RECRUITING

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, , Poland

Site Status RECRUITING

CCA Hospital Braga

Braga, , Portugal

Site Status RECRUITING

Hospital Nélio Mendonça

Funchal, , Portugal

Site Status RECRUITING

Centro Hospitalar do Porto

Porto, , Portugal

Site Status RECRUITING

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocio - PPDS

Seville, , Spain

Site Status RECRUITING

Karolinska Universitetssjukhuset Huddinge

Huddinge, , Sweden

Site Status RECRUITING

Universitetssjukhuset i Linköping

Linköping, , Sweden

Site Status RECRUITING

Inselspital Bern

Bern, , Switzerland

Site Status RECRUITING

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Site Status RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

King's College Hospital

London, , United Kingdom

Site Status RECRUITING

Queen's Medical Centre

Nottingham, , United Kingdom

Site Status WITHDRAWN

Derriford Hospital

Plymouth, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Austria Belgium Brazil Canada Czechia Denmark France Germany Italy Netherlands Poland Portugal Spain Sweden Switzerland United Kingdom

Central Contacts

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Takeda Contact

Role: CONTACT

1-877-825-3327

Facility Contacts

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Site Contact

Role: primary

205-934-9999

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602-406-7791

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507-284-9523

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520-626-3005

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858-657-7076

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310-825-6170

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415-353-7052

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212-263-3643

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216-983-0879

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717-531-6525

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215-707-5067

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843-792-5300

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903-957-0417

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Related Links

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Other Identifiers

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2022-501943-34-00

Identifier Type: CTIS

Identifier Source: secondary_id

TAK-999-3001

Identifier Type: -

Identifier Source: org_study_id

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