Recruiting

Phase 3

FazirsiranStudy 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

Code:

NCT05677971

Conditions

Alpha1-Antitrypsin Deficiency

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Fazirsiran Injection

Placebo

Study Details

Brief 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.

Conditions

Alpha1-Antitrypsin Deficiency

Study ID

NCT05677971

Start date

Mar 6, 2023

Status verified date

May, 2026

Completion date

Dec 12, 2031

Anticipated

Primary completion date

Jan 17, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

160 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

placebo comparator: Placebo

Participants will receive placebo on Day 1, at Week 4, and Q12 W thereafter up to Week 196.

Interventions

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.

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 ]

Central Contacts and Locations

Central contacts

Takeda Contact

1-877-825-3327 medinfoUS@takeda.com

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Site Contact

205-934-9999 grayme@uab.edu

Principal Investigator:

Meagan Gray

St. Joseph's Hospital and Medical Center

Recruiting

Phoenix, Arizona, United States, 85013

Contacts

Site Contact

602-406-7791 nilofar.najafian@commonspirit.org

Principal Investigator:

Nilofar Najafian

Mayo Clinic

Recruiting

Phoenix, Arizona, United States, 85054-4502

Contacts

Site Contact

507-284-9523 vargas.hugo@mayo.edu

Principal Investigator:

Hugo Vargas

University of California San Diego, Altman Clinical and Translational Institute

Recruiting

La Jolla, California, United States, 92093

Contacts

Site Contact

858-657-7076 roloomba@health.ucsd.edu

Principal Investigator:

Rohit Loomba

UCLA Pulmonary and Critical Care

Recruiting

Los Angeles, California, United States, 90095-8344

Contacts

Site Contact

310-825-6170 ibarjaktarevic@mednet.ucla.edu

Principal Investigator:

Igor Barjaktarevic

Stanford University

Recruiting

Palo Alto, California, United States, 94303

Contacts

Site Contact

650-723-6381 pkwo@stanford.edu

Principal Investigator:

Paul Kwo

University of California Benioff Children's Hospital

Recruiting

San Francisco, California, United States, 94143

Contacts

Site Contact

415-353-7052 PROSENTH@ucsf.edu

Principal Investigator:

Philip Rosenthal

Peak Gastroenterology Associates, PC

Recruiting

Colorado Springs, Colorado, United States, 80907

Contacts

Site Contact

719-310-6719 bpatel@peakgastro.com

Principal Investigator:

Bhaktasharan Patel

University of Florida

Recruiting

Gainesville, Florida, United States, 32611

Contacts

Site Contact

352-294-5152 briana.foerman@medicine.ufl.edu

Principal Investigator:

Virginia Clark

Schiff Center for Liver Diseases/University of Miami

Recruiting

Miami, Florida, United States, 33136-1051

Contacts

Site Contact

305-243-1020 eschiff@med.miami.edu

Principal Investigator:

Eugene Schiff

Indiana University School of Medicine - Indianapolis

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Site Contact

317-278-6215 rvuppala@iu.edu; mandcruz@iu.edu

Principal Investigator:

Raj Vuppalanchi

University of Iowa Hospitals and Clinics

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Site Contact

319-356-2577 tomohiro-tanaka@uiowa.edu

Principal Investigator:

Tomohiro Tanaka

Ochsner Medical Center

Recruiting

New Orleans, Louisiana, United States, 70121-2429

Contacts

Site Contact

504-842-3925 gtherapondos@ochsner.org

Principal Investigator:

George Therapondos

University of Maryland Medical Center

Recruiting

Baltimore, Maryland, United States, 21201-1504

Contacts

Site Contact

410-328-1358 kshetty@som.umaryland.edu

Principal Investigator:

Kirti Shetty

Brigham and Womens Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Site Contact

617-525-1267 NHASHEMI@BWH.HARVARD.EDU

Principal Investigator:

Nikroo Hashemi

Boston Medical Center

Recruiting

Boston, Massachusetts, United States, 02118-2908

Contacts

Site Contact

617-638-8000 amohanty@bu.edu

Principal Investigator:

Arpan Mohanty

University of Michigan Hospital

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Site Contact

734-232-3741 rfontana@med.umich.edu

Principal Investigator:

Robert Fontana

Henry Ford Medical Center - Columbus

Recruiting

Novi, Michigan, United States, 48377-3600

Contacts

Site Contact

248-344-6688 sgordon3@hfhs.org

Principal Investigator:

Stuart Gordon

Mayo Clinic - PPDS

Recruiting

Rochester, Minnesota, United States, 55905-0001

Contacts

Site Contact

507-284-0686 malhi.harmeet@mayo.edu

Principal Investigator:

Harmeet Malhi

Cardinal Glennon Children's Hospital

Recruiting

St Louis, Missouri, United States, 63104-1003

Contacts

Site Contact

314-577-5633 jeffrey.teckman@slucare.ssmhealth.com

Principal Investigator:

Jeffery Teckman

Washington University School of Medicine in St. Louis

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Contact

314-454-8025 smeduchenry@wustl.edu

Principal Investigator:

Scott McHenry

NYU Langone Health

Recruiting

New York, New York, United States, 10016

Contacts

Site Contact

212-263-3643 viviana.figueroadiaz@nyulangone.org

Principal Investigator:

Viviana Figueroa Diaz

Columbia University Irving Medical Center

Recruiting

New York, New York, United States, 10032-3722

Contacts

Site Contact

212-305-2862 mpg2124@cumc.columbia.edu

Principal Investigator:

Monica Goldklang

University Hospitals Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106-1716

Contacts

Site Contact

216-983-0879 seth.sclair@uhhospitals.org

Principal Investigator:

Seth Sclair

Penn State Health Milton S. Hershey Medical Center

Recruiting

Hershey, Pennsylvania, United States, 17033

Contacts

Site Contact

717-531-6525 tcraig@pennstatehealth.psu.edu

Principal Investigator:

Timothy Craig

Temple University Hospital

Recruiting

Philadelphia, Pennsylvania, United States, 19140-5103

Contacts

Site Contact

215-707-5067 yedidya.saiman@tuhs.temple.edu

Principal Investigator:

Yedidya Saiman

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Site Contact

843-792-5300 strangec@musc.edu

Principal Investigator:

Charlie Strange

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232-0028

Contacts

Site Contact

615-322-8748 roman.perri@vumc.org

Principal Investigator:

Roman Perri

Texoma Liver Center

Recruiting

Denison, Texas, United States, 75020

Contacts

Site Contact

903-957-0417 h.elgouhari@somacinicaltrials.com

Principal Investigator:

Hesham Elgouhari

Baylor College of Medicine Medical Center

Recruiting

Houston, Texas, United States, 77030-4202

Contacts

Site Contact

832-355-1400 george.cholankeril@bcm.edu

Principal Investigator:

George Cholankeril

The Texas Liver Institute

Recruiting

San Antonio, Texas, United States, 78215

Contacts

Site Contact

210-253-3426 lawitz@txliver.com

Principal Investigator:

Eric Lawitz

Bon Secours St. Mary's Hospital

Recruiting

Richmond, Virginia, United States, 23226

Contacts

Site Contact

804-977-8920 mitchell_shiffman@bshsi.org

Principal Investigator:

Mitchell Shiffman

VCU Medical Center North Hospital

Recruiting

Richmond, Virginia, United States, 23298-5028

Contacts

Site Contact

212-824-7587 amon.asgharpour@vcuhealth.org

Principal Investigator:

Amon Asgharpour

GI Research Institute

Recruiting

Vancouver, British Columbia, Canada, V6Z 2K5

Contacts

Site Contact

6046886332 hinnih@gmail.com

Principal Investigator:

Hin Hin Ko

Queen Elizabeth II Health Sciences Center

Recruiting

Halifax, Nova Scotia, Canada, B3H 2Y9

Contacts

Site Contact

julie.zhu@nshealth.ca

Principal Investigator:

Julie Zhu

Inspiration Research Limited

Recruiting

Toronto, Ontario, Canada, M5T 3A9

Contacts

Site Contact

(416) 944-9602 kchapman@inspirationresearch.ca

Principal Investigator:

Kenneth Chapman

More Information

Sponsor

Takeda

Last update posted

May 13, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Takeda on 2026-05-13.