AzTrials
AzTrials

Alpha1-Antitrypsin DeficiencyPhase 3NCT05677971

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

A Phase 3 study testing Fazirsiran Injection in people with Alpha1-Antitrypsin Deficiency, run by Takeda at 89 sites in 19 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Alpha1-Antitrypsin Deficiency
What is being tested?
Fazirsiran Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
160 participants
Where
89 sitesin 19 countries
Study dates
6 Mar 2023to 12 Dec 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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]).
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  • 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.

Trial locations and contacts

89 sites in 19 countries. Contact the study team or a site near you to ask about taking part.

Takeda Contact contact

1-877-825-3327

medinfoUS@takeda.com

89 sites in 19 countries

United States37 sites, 33 recruiting

  • University of Michigan Hospital

    Ann Arbor, Michigan, 48109

    Site Contact, 734-232-3741, rfontana@med.umich.edu

    Robert Fontana

    Recruiting

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30329

    Withdrawn

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201-1504

    Site Contact, 410-328-1358, kshetty@som.umaryland.edu

    Kirti Shetty

    Recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

    Site Contact, 205-934-9999, grayme@uab.edu

    Meagan Gray

    Recruiting

  • Brigham and Womens Hospital

    Boston, Massachusetts, 02115

    Site Contact, 617-525-1267, NHASHEMI@BWH.HARVARD.EDU

    Nikroo Hashemi

    Recruiting

  • Boston Medical Center

    Boston, Massachusetts, 02118-2908

    Site Contact, 617-638-8000, amohanty@bu.edu

    Arpan Mohanty

    Recruiting

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

    Site Contact, 843-792-5300, strangec@musc.edu

    Charlie Strange

    Recruiting

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106-1716

    Site Contact, 216-983-0879, seth.sclair@uhhospitals.org

    Seth Sclair

    Recruiting

  • Peak Gastroenterology Associates, PC

    Colorado Springs, Colorado, 80907

    Site Contact, 719-310-6719, bpatel@peakgastro.com

    Bhaktasharan Patel

    Recruiting

  • Texoma Liver Center

    Denison, Texas, 75020

    Site Contact, 903-957-0417, h.elgouhari@somacinicaltrials.com

    Hesham Elgouhari

    Recruiting

  • Gastroenterology & Liver Institute

    Escondido, California, 92025

    Withdrawn

  • University of Florida

    Gainesville, Florida, 32611

    Site Contact, 352-294-5152, briana.foerman@medicine.ufl.edu

    Virginia Clark

    Recruiting

  • Penn State Health Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

    Site Contact, 717-531-6525, tcraig@pennstatehealth.psu.edu

    Timothy Craig

    Recruiting

  • Baylor College of Medicine Medical Center

    Houston, Texas, 77030-4202

    Site Contact, 832-355-1400, george.cholankeril@bcm.edu

    George Cholankeril

    Recruiting

  • Indiana University School of Medicine - Indianapolis

    Indianapolis, Indiana, 46202

    Site Contact, 317-278-6215, rvuppala@iu.edu; mandcruz@iu.edu

    Raj Vuppalanchi

    Recruiting

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

    Site Contact, 319-356-2577, tomohiro-tanaka@uiowa.edu

    Tomohiro Tanaka

    Recruiting

  • University of California San Diego, Altman Clinical and Translational Institute

    La Jolla, California, 92093

    Site Contact, 858-657-7076, roloomba@health.ucsd.edu

    Rohit Loomba

    Recruiting

  • UCLA Pulmonary and Critical Care

    Los Angeles, California, 90095-8344

    Site Contact, 310-825-6170, ibarjaktarevic@mednet.ucla.edu

    Igor Barjaktarevic

    Recruiting

  • Schiff Center for Liver Diseases/University of Miami

    Miami, Florida, 33136-1051

    Site Contact, 305-243-1020, eschiff@med.miami.edu

    Eugene Schiff

    Recruiting

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-0028

    Site Contact, 615-322-8748, roman.perri@vumc.org

    Roman Perri

    Recruiting

  • Ochsner Medical Center

    New Orleans, Louisiana, 70121-2429

    Site Contact, 504-842-3925, gtherapondos@ochsner.org

    George Therapondos

    Recruiting

  • NYU Langone Health

    New York, New York, 10016

    Site Contact, 212-263-3643, viviana.figueroadiaz@nyulangone.org

    Viviana Figueroa Diaz

    Recruiting

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

    New York, New York, 10032-1559

    Withdrawn

  • Columbia University Irving Medical Center

    New York, New York, 10032-3722

    Site Contact, 212-305-2862, mpg2124@cumc.columbia.edu

    Monica Goldklang

    Recruiting

  • Henry Ford Medical Center - Columbus

    Novi, Michigan, 48377-3600

    Site Contact, 248-344-6688, sgordon3@hfhs.org

    Stuart Gordon

    Recruiting

  • Stanford University

    Palo Alto, California, 94303

    Site Contact, 650-723-6381, pkwo@stanford.edu

    Paul Kwo

    Recruiting

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140-5103

    Site Contact, 215-707-5067, yedidya.saiman@tuhs.temple.edu

    Yedidya Saiman

    Recruiting

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

    Site Contact, 602-406-7791, nilofar.najafian@commonspirit.org

    Nilofar Najafian

    Recruiting

  • Mayo Clinic

    Phoenix, Arizona, 85054-4502

    Site Contact, 507-284-9523, vargas.hugo@mayo.edu

    Hugo Vargas

    Recruiting

  • Bon Secours St. Mary's Hospital

    Richmond, Virginia, 23226

    Site Contact, 804-977-8920, mitchell_shiffman@bshsi.org

    Mitchell Shiffman

    Recruiting

  • VCU Medical Center North Hospital

    Richmond, Virginia, 23298-5028

    Site Contact, 212-824-7587, amon.asgharpour@vcuhealth.org

    Amon Asgharpour

    Recruiting

  • Mayo Clinic - PPDS

    Rochester, Minnesota, 55905-0001

    Site Contact, 507-284-0686, malhi.harmeet@mayo.edu

    Harmeet Malhi

    Recruiting

  • The Texas Liver Institute

    San Antonio, Texas, 78215

    Site Contact, 210-253-3426, lawitz@txliver.com

    Eric Lawitz

    Recruiting

  • University of California Benioff Children's Hospital

    San Francisco, California, 94143

    Site Contact, 415-353-7052, PROSENTH@ucsf.edu

    Philip Rosenthal

    Recruiting

  • Cardinal Glennon Children's Hospital

    St Louis, Missouri, 63104-1003

    Site Contact, 314-577-5633, jeffrey.teckman@slucare.ssmhealth.com

    Jeffery Teckman

    Recruiting

  • Washington University School of Medicine in St. Louis

    St Louis, Missouri, 63110

    Site Contact, 314-454-8025, smeduchenry@wustl.edu

    Scott McHenry

    Recruiting

  • University of Arizona Thomas D. Boyer Liver Institute

    Tucson, Arizona, 85724-5136

    Withdrawn

Other trials in United States

France6 sites, 6 recruiting

  • Hôpital Beaujon

    Clichy, 92110

    Site Contact, +33140875875, kathleenlourdes.milord@aphp.fr

    Kathleen Milord

    Recruiting

  • Hôpital de La Croix Rousse

    Lyon, 69317

    Site Contact, +33426732654, teresa.antonini@chu-lyon.fr

    Teresa Antonini

    Recruiting

  • Centre Francois Magendie

    Pessac, 33064

    Site Contact, +338888888888, maeva.zysman@chu-bordeaux.fr

    Maeva Zysman

    Recruiting

  • Hopital PONTCHAILLOU CHU de Rennes

    Rennes, 35000

    Site Contact, +33299284298, edouard.bardou-jacquet@chu-rennes.fr

    Edouard Bardou-Jacquet

    Recruiting

  • Hospital Purpan

    Toulouse, 31000

    Site Contact, +33561779105, alric.l@chu-toulouse.fr

    Lauren Alric

    Recruiting

  • Hôpital Paul Brousse

    Val-de-Marne, 94805

    Site Contact, +33145593336, audrey.coilly@aphp.fr

    Audrey Coilly

    Recruiting

Other trials in France

United Kingdom6 sites, 5 recruiting

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

    Site Contact, +4401223586891, Bill.griffiths@nhs.net

    Willliam Griffiths

    Recruiting

  • Royal Infirmary of Edinburgh

    Edinburgh, EH16 4SA

    Site Contact, +441315361000, michael.williams@nhslothian.scot.nhs.uk

    Michael Williams

    Recruiting

  • Royal Free Hospital

    London, NW3 2Q

    Site Contact, +442037582000t35218, aileen.marshall@nhs.net

    Aileen Marshall

    Recruiting

  • King's College Hospital

    London, SE5 9RS

    Site Contact, +442032991019, aftab.ala1@nhs.net

    Aftab Ala

    Recruiting

  • Queen's Medical Centre

    Nottingham, NG7 2UH

    Withdrawn

  • Derriford Hospital

    Plymouth, PL6 8DH

    Site Contact, +441752792555, ashwin.dhanda@nhs.net

    Ashwin Dhanda

    Recruiting

Other trials in United Kingdom

Germany5 sites, 5 recruiting

  • Universitätsklinikum der RWTH Aachen

    Aachen, 52074

    Site Contact, +492418035324, pstrnad@ukaachen.de

    Pavel Strnad

    Recruiting

  • Charité - Campus Virchow-Klinikum-Ostring 1

    Berlin, 13353

    Site Contact, +4939450553022, frank.tacke@charite.de

    Frank Tacke

    Recruiting

  • Hannover Medical School

    Hanover, 30625

    Site Contact, +495115323306, wedemeyer.heiner@mh-hannover.de

    Heiner Wedemeyer

    Recruiting

  • Universitätsklinikum Schleswig-Holstein - Campus Kiel

    Kiel, 24105

    Site Contact, +4943150022406, rainer.guenther@uksh.de

    Rainer Günther

    Recruiting

  • Universitätsklinikum Tübingen

    Tübingen, 72076

    Site Contact, +4970712986677, christoph.berg@med.uni-tuebingen.de

    Christoph Berg

    Recruiting

Other trials in Germany

Austria4 sites, 4 recruiting

  • LKH-Universitätsklinikum Graz

    Graz, 8036

    Site Contact, +4331638580287, martin.wagner@medunigraz.at

    Martin Wagner

    Recruiting

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

    Site Contact, +4351250482830, heinz.zoller@i-med.ac.at; hepa-studyteam@i-med.ac.at

    Heinz Zoller

    Recruiting

  • Klinikum Klagenfurt Am Wörthersee

    Klagenfurt, 9020

    Site Contact, +4346353831103, markus@peck.at

    Markus Peck-Radosavljevic

    Recruiting

  • Medizinische Universität Wien (Medical University of Vienna)

    Vienna, 1090

    Site Contact, +43140400-43910, mattias.mandorfer@meduniwien.ac.at

    Mattias Mandorfer

    Recruiting

Other trials in Austria

Italy4 sites, 4 recruiting

  • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

    Milan, 20122

    Site Contact, +390255033516, luca.valenti@policlinico.mi.it

    Luca Valenti

    Recruiting

  • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

    Palermo, 90127

    Site Contact, +3909123890679, vincenza.calvaruso@unipa.it

    Vincenza Calvaruso

    Recruiting

  • Fondazione IRCCS Policlinico San Matteo di Pavia

    Pavia, 27100

    Site Contact, +390382503777, corsico@unipv.it

    Angelo Corsico

    Recruiting

  • IRCCS Istituto Clinico Humanitas

    Rozzano, 20089

    Site Contact, +390282243788, alessio.aghemo@humanitasresearch.it

    Alessio Aghemo

    Recruiting

Other trials in Italy

Spain4 sites, 4 recruiting

  • Hospital Universitario Vall d'Hebron - PPDS

    Barcelona, 8025

    Site Contact, +34932742779, monica.pons@vhir.org

    Monica Pons Delgado

    Recruiting

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29071

    Site Contact, +34951022735, andrade@uma.es

    Raul Andrade

    Recruiting

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

    Site Contact, +34942204089, alvaro.diaz@scsalud.es

    Alvaro Gonzalez

    Recruiting

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville, 41013

    Site Contact, +34955013068, mromerogomez@us.es

    Manuel Romero Gómez

    Recruiting

Other trials in Spain

Brazil3 sites, 3 recruiting

  • Hospital de Base do Distrito Federal

    Brasília, 71692-000

    Site Contact, +556184013142, mendesliliana2@gmail.com

    Liliana Mendes Sampaio Costa

    Recruiting

  • Hospital Sirio-Libanes

    São Paulo, 01308-050

    Site Contact, +551133945297, gildaporta@gmail.com

    Gilda Porta

    Recruiting

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

    São Paulo, 18618-687

    Site Contact, +551438822238, fgromeiro@gmail.com

    Fernando Romeiro Gomes

    Recruiting

Other trials in Brazil

Canada3 sites, 3 recruiting

  • Queen Elizabeth II Health Sciences Center

    Halifax, Nova Scotia, B3H 2Y9

    Site Contact, julie.zhu@nshealth.ca

    Julie Zhu

    Recruiting

  • Inspiration Research Limited

    Toronto, Ontario, M5T 3A9

    Site Contact, (416) 944-9602, kchapman@inspirationresearch.ca

    Kenneth Chapman

    Recruiting

  • GI Research Institute

    Vancouver, British Columbia, V6Z 2K5

    Site Contact, 6046886332, hinnih@gmail.com

    Hin Hin Ko

    Recruiting

Other trials in Canada

Portugal3 sites, 3 recruiting

  • CCA Hospital Braga

    Braga, 4710-243

    Site Contact, +351253027000, crolanda@med.uminho.pt

    Carla Rolanda

    Recruiting

  • Hospital Nélio Mendonça

    Funchal, 9000-168

    Site Contact, +351291705600, magnovitorp@gmail.com

    Vitor Pereira

    Recruiting

  • Centro Hospitalar do Porto

    Porto, 4099-003

    Site Contact, +351222077500, luisazevedomaia@hotmail.com

    Luis Maia

    Recruiting

Other trials in Portugal

Australia2 sites, 1 recruiting

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

    Withdrawn

  • St Vincents Hospital Melbourne - PPDS

    Fitzroy, Victoria, 3065

    Site Contact, +61392312211, matthew.conron@svha.org.au

    Matthew Conron

    Recruiting

Other trials in Australia

Belgium2 sites, 2 recruiting

  • UZ Antwerpen

    Antwerp, 2650

    Site Contact, +3238213000, sven.francque@uza.be

    Sven Francque

    Recruiting

  • UZ Leuven

    Leuven, 3000

    Site Contact, +3216345500, jef.verbeek@uzleuven.be

    Jef Verbeek

    Recruiting

Other trials in Belgium

Netherlands2 sites, 1 recruiting

  • Amsterdam UMC - VUmc - De Boelelaan

    Amsterdam, 1081 HV

    Withdrawn

  • Leiden University Medical Center

    Leiden, 2333 ZA

    Site Contact, +31715296987, e.f.a.van_t_wout@lumc.nl

    Emily F.A. van 't Wout

    Recruiting

Other trials in Netherlands

Poland2 sites, 1 recruiting

  • ID Clinic Arkadiusz Pisula

    Śląskie, 41-400

    Withdrawn

  • WIP Warsaw IBD Point Profesor Kierkus

    Warsaw, 00-728

    Site Contact, +48500111648, j.kierkus@wip.waw.pl

    Jaroslaw Kierkus

    Recruiting

Other trials in Poland

Sweden2 sites, 2 recruiting

  • Karolinska Universitetssjukhuset Huddinge

    Huddinge, 14186

    Site Contact, +46858580000, staffan.wahlin@ki.se

    Staffan Wahlin

    Recruiting

  • Universitetssjukhuset i Linköping

    Linköping, 581 85

    Site Contact, +46101030000, mattias.ekstedt@liu.se

    Mattias Ekstedt

    Recruiting

Other trials in Sweden

Czechia1 site, 1 recruiting

  • Institut klinicke a experimentalni mediciny

    Prague, 140 21

    Site Contact, +420261363387, jan.sperl@ikem.cz

    Jan Sperl

    Recruiting

Other trials in Czechia

Denmark1 site, 1 recruiting

  • Hvidovre Hospital

    Hvidovre, 2650

    Site Contact, +4530527312, elias.badal.rashu@regionh.dk

    Elias Rashu

    Recruiting

Other trials in Denmark

Ireland1 site, 1 recruiting

  • Beaumont Hospital

    Dublin, D09 YD60

    Site Contact, +3538888888888, gmcelvaney@rcsi.ie

    Noel McElvaney

    Recruiting

Other trials in Ireland

Switzerland1 site, 1 recruiting

  • Inselspital Bern

    Bern, 3010

    Site Contact, +41 31 632 59 33, studien.hepatologie@insel.ch

    Guido Stirnimann

    Recruiting

Other trials in Switzerland

About 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

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.

Being tested
Fazirsiran Injection, Placebo
Medical subject headings
alpha 1-Antitrypsin Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fazirsiran InjectionDrug

    Also called TAK-999, ARO-AAT, ADS-001

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

  • PlaceboOther

    Also called Sodium chloride

    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 groups in NCT05677971
Study groupRoleWhat they receive
FazirsiranExperimentalParticipants 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.
Receives: Drug: Fazirsiran Injection
PlaceboPlacebo comparatorParticipants will receive placebo on Day 1, at Week 4, and Q12 W thereafter up to Week 196.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction From Baseline of at Least 1 Stage of Histologic Fibrosis (METAVIR Staging) in the Centrally Read Liver Biopsy at Week 106 in AATD-LD With METAVIR Stage F2 and F3 Fibrosis

    Reduction from baseline of at least 1 stage of histologic fibrosis METAVIR staging in the centrally read liver biopsy at Week 106 in AATD-LD with METAVIR stage F2 and F3 fibrosis will be assessed.

    Measured: Baseline, Week 106

Secondary outcomes (17)

  1. Percent Change from Baseline in Intrahepatic Z-AAT Protein in Alpha-1 Antitrypsin Deficiency-Associated Liver Disease (AATD-LD) with METAVIR Stage F2 to F3 Fibrosis at Week 106

    Percent change from baseline in intrahepatic Z-AAT protein in AATD-LD with METAVIR stage F2 to F3 fibrosis will be assessed.

    Measured: Baseline, Week 106

  2. Reduction From Baseline of at Least 1 Stage of Histologic Fibrosis (METAVIR Staging) in the Centrally Read Liver Biopsy

    Reduction from baseline of at least 1 stage of histologic fibrosis (METAVIR Staging) in the centrally read liver biopsy in participants with AATD-LD with METAVIR stage fibrosis will be assessed.

    Measured: Baseline, Week 106 and Week 202

  3. Number of Participants With Liver Related Clinical Events up to Week 202

    Number of participants with any qualifying liver-related clinical events up to Week 202 in AATD-LD with METAVIR stage F2 to F4 fibrosis will be assessed.

    Measured: Baseline up to Week 202

  4. Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) Protein

    Change from baseline in serum Z-AAT protein in participants with AATD-LD with METAVIR stage fibrosis will be assessed.

    Measured: Baseline, Week 106, Week 202

  5. Change From Baseline in Intrahepatic Z-AAT Protein Polymer Burden Assessed by Periodic Acid Schiff Plus Diastase (PAS+D) Staining

    Change from baseline in intrahepatic Z-AAT protein polymer burden assessed by PAS+D staining liver biopsy in participants with AATD-LD with METAVIR stage fibrosis will be assessed.

    Measured: Baseline, Week 106, Week 202

  6. Change From Baseline in Intrahepatic Portal Inflammation

    Change from baseline in intrahepatic portal inflammation liver biopsy in participants with AATD-LD with METAVIR stage fibrosis will be assessed.

    Measured: Baseline, Week 106, Week 202

  7. Change From Baseline in Vibration-Controlled Transient Elastography (VCTE)/Magnetic Resonance Elastography (MRE)-derived Liver Stiffness

    Change from baseline in VCTE/MRE-derived liver stiffness in participants with AATD-LD with METAVIR stage fibrosis will be assessed.

    Measured: Baseline, Week 106, Week 196 and Week 202

  8. Change From Baseline in Model of End-Stage Liver Disease (MELD) Score

    The MELD scoring system is used to assess the severity of chronic liver disease. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78*log e serum bilirubin (milligram per deciliter [mg/dL]) + 11.20* log e INR + 9.57* log e serum creatinine (mg/dL) + 6.43 (constant for liver disease etiology). The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome. Change from baseline in MELD score in participants with AATD-LD with METAVIR stage fibrosis will be assessed.

    Measured: Baseline, Week 106, and Week 202

  9. Change From Baseline in Liver Injury

    Change from baseline in liver injury in participants with AATD-LD with METAVIR stage fibrosis will be assessed.

    Measured: Baseline, Week 106 and Week 202

  10. Percent Change from Baseline in Intrahepatic Z-AAT Protein in AATD-LD With METAVIR Stage F2 to F4 Fibrosis

    Percent change from baseline in intrahepatic Z-AAT protein in AATD-LD with METAVIR stage F2 to F4 fibrosis will be assessed.

    Measured: Baseline, Week 106 and Week 202

  11. Observed Plasma Concentrations of Fazirsiran

    Observed Plasma Concentrations of Fazirsiran will be assessed.

    Measured: Pre-dose up to Week 220

  12. Number of Participants with Treatment-emergent adverse event (TEAE) and Serious TEAEs

    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. An SAE is any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. A TEAE is any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. Number of participants with TEAEs and serious TEAEs will be assessed.

    Measured: From start of study drug administration up to end of the study (EOS) (Week 230)

  13. Number of Participants with Clinically Significant Declines in Lung Function Parameters

    Standard pulmonary function parameters measured will be used to study lung function.

    Measured: From start of study drug administration up to EOS (Week 230)

  14. Change From Baseline in Whole Lung PD15 (15th percentile point) Measured by CT lung Densitometry

    Change from baseline in whole lung PD15 (15th percentile point) as measured by CT lung densitometry will be assessed.

    Measured: Baseline up to Week 196

  15. Number of Participants with Clinically Significant Change in Vital Signs

    Vital signs will include body temperature, respiratory rate, blood pressure, pulse and amount of oxygen in the blood. Any change in vital signs which are deemed clinically significant by the investigator will be reported as AE.

    Measured: From start of study drug administration up to EOS (Week 230)

  16. Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters

    12-lead ECG will be evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator will be reported as AE.

    Measured: From start of study drug administration up to EOS (Week 230)

  17. Number of Participants with Clinically Significant Changes in Clinical Laboratory Assessments

    Clinical laboratory assessments include hematology, serum chemistry, coagulation, and urinalysis. Changes in laboratory values may be considered as AE if they were judged to be clinically significant.

    Measured: From start of study drug administration up to EOS (Week 230)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2023
  2. Study start6 Mar 2023
  3. Primary completion17 Jan 2029 (estimated)
  4. Study completion12 Dec 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05677971
Sponsor's protocol ID
TAK-999-3001
Other IDs
2022-501943-34-00
Status last verified
May 2026
First submitted
28 Dec 2022
Last updated
13 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fazirsiran Injection in people with Alpha1-Antitrypsin Deficiency, run by Takeda at 89 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 89 sites in United States, France, United Kingdom, Germany, Austria and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Takeda Contact (1-877-825-3327, medinfoUS@takeda.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction From Baseline of at Least 1 Stage of Histologic Fibrosis (METAVIR Staging) in the Centrally Read Liver Biopsy at Week 106 in AATD-LD With METAVIR Stage F2 and F3 Fibrosis (time frame: Baseline, Week 106). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05677971.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.

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