Actively Recruiting
Study to Learn About the Safety of Fazirsiran and if it Can Help People With Alpha-1 Antitrypsin Liver Disease With Mild Liver Scarring (Fibrosis)
Led by Takeda · Updated on 2026-03-05
50
Participants Needed
41
Research Sites
234 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
The liver produces a protein called alpha-1 antitrypsin (AAT). AAT is normally released into the bloodstream. In some people, the liver makes an abnormal version of the AAT protein, called Z-AAT. Making an abnormal version of the AAT protein can result in liver disease as Z-AAT builds up in liver cells, which leads to liver problems such as liver scarring (fibrosis), continuing liver damage (cirrhosis), and eventually end stage liver disease. Fazirsiran is a medicine that reduces the creation of the Z-AAT protein and thus the build-up of this abnormal protein in the liver. People with this type of liver disease who already have mild liver scarring will take part in the study. They will be treated with fazirsiran or a placebo for about 2 years. This study will check the long-term safety of fazirsiran, whether participants tolerate the treatment and if there are any effects on liver scarring. A liver biopsy, a way of collecting a small tissue sample from the liver, will be taken twice during the study.
CONDITIONS
Official Title
Study to Learn About the Safety of Fazirsiran and if it Can Help People With Alpha-1 Antitrypsin Liver Disease With Mild Liver Scarring (Fibrosis)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participant is able to understand and follow the study requirements and schedule.
- Participant can read, understand, and complete electronic study questionnaires.
- Participant signs a written informed consent form and any required privacy authorizations.
- Participant is aged 18 to 75 years, inclusive.
- Participant has a confirmed diagnosis of the PiZZ genotype alpha-1 antitrypsin deficiency.
- Participant has liver biopsy core samples collected as required by the protocol.
- Participant shows evidence of METAVIR stage F1 liver fibrosis confirmed by a recent liver biopsy.
- Participant meets pulmonary status requirements as defined by the protocol.
- Participant does not have hepatocellular carcinoma (HCC).
- Participants taking certain medications (statins, ACE inhibitors, angiotensin II receptor blockers, beta-1 selective blockers) must be on stable doses for at least 8 weeks before randomization and continue during the study.
- Participant's body mass index (BMI) is between 18 and 39 kg/m².
- Participant has a normal 12-lead electrocardiogram without safety concerns.
- Participant is a nonsmoker.
- If treated with respiratory medications, doses must be stable for at least 4 weeks before screening.
- Participant has suitable venous access for blood sampling.
- Female participants of childbearing potential must have negative pregnancy tests at screening and before dosing.
- Participants of childbearing potential must use effective contraception during the study and for 6 months after the last dose, and males must not donate sperm for 6 months after last dose.
You will not qualify if you...
- Participant has liver fibrosis stage F2 or higher based on biopsy.
- History of liver decompensation events.
- History of varices detected by previous endoscopy.
- Presence of portal vein thrombosis.
- Prior trans-jugular portosystemic shunt procedure.
- Evidence of other chronic liver diseases.
- History of malignancy within 5 years, except certain treated skin, bladder, or cervical cancers.
- Abnormal clinical findings or laboratory abnormalities that could affect safety or study results.
- Expected high-level exposure to inhaled lung toxins during the study.
- Recent lower respiratory tract infection within 6 months.
- History of frequent pulmonary exacerbations or current exacerbation.
- Use of long-term oxygen therapy or CPAP/BiPAP for acute respiratory failure.
- HIV infection or active hepatitis B or C infection.
- Unstable or severe hypertension.
- History of certain heart rhythm disorders or severe cardiovascular disease.
- History of major surgery within 12 weeks before screening.
- History of significant alcohol or drug abuse.
- Previous treatment with fazirsiran or other RNA interference therapies for this condition.
- Allergies or hypersensitivity to fazirsiran or its components.
- Recent participation in other investigational studies or recent blood donation.
- Medical, psychiatric, or social conditions that could affect compliance or safety.
- Recent thromboembolic disease or chronic anticoagulant use.
- Inability to attend all scheduled study visits.
- Current or unresolved COVID-19 infection.
- Study site employees or immediate family members involved in the study.
- Pregnancy, breastfeeding, or intent to become pregnant or donate ova during the study or within 6 months after last dose.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 41 locations
1
St Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013-4224
Actively Recruiting
2
Mayo Clinic - PPDS
Phoenix, Arizona, United States, 85054-4502
Actively Recruiting
3
University of Arizona Thomas D. Boyer Liver Institute
Tucson, Arizona, United States, 85724-0001
Actively Recruiting
4
University of California San Diego
La Jolla, California, United States, 92037-1337
Actively Recruiting
5
UCLA Pulmonary and Critical Care
Los Angeles, California, United States, 90095-3075
Actively Recruiting
6
University of California Benioff Children's Hospital
San Francisco, California, United States, 94143-2203
Actively Recruiting
7
Peak Gastroenterology Associates
Colorado Springs, Colorado, United States, 80907
Actively Recruiting
8
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, United States, 33136
Actively Recruiting
9
Indiana University School of Medicine-Indianapolis
Indianapolis, Indiana, United States, 46202-2266
Actively Recruiting
10
University Of Iowa Hospitals And Clinics
Iowa City, Iowa, United States, 52242-1009
Actively Recruiting
11
Boston Medical Center
Boston, Massachusetts, United States, 02118-2335
Actively Recruiting
12
University of Michigan Hospital - 1500 E Medical Center Dr
Ann Arbor, Michigan, United States, 48109
Actively Recruiting
13
Henry Ford Health System
Novi, Michigan, United States, 48377-3600
Actively Recruiting
14
Mayo Clinic PPDS
Rochester, Minnesota, United States, 55905
Actively Recruiting
15
NYU Langone Medical Center
New York, New York, United States, 10016-6402
Actively Recruiting
16
Columbia University Irving Medical Center
New York, New York, United States, 10032-3722
Actively Recruiting
17
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106-1716
Actively Recruiting
18
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-2360
Actively Recruiting
19
Texas Liver Institute American Research Corporation
San Antonio, Texas, United States, 78215
Actively Recruiting
20
Bon Secours St. Mary's Hospital
Newport, Virginia, United States, 23602-4414
Actively Recruiting
21
LKH-Universitätsklinikum Graz
Graz, Austria, 8036
Actively Recruiting
22
KABEG - Klinikum Klagenfurt Am Wörthersee
Klagenfurt, Austria, 9020
Actively Recruiting
23
UZ Antwerpen
Antwerp, Belgium, 2650
Actively Recruiting
24
UZ Leuven
Leuven, Belgium, 3000
Actively Recruiting
25
Inspiration Research Limited
Toronto, Ontario, Canada, M5T 3A9
Actively Recruiting
26
Hôpital de La Croix Rousse
Lyon, France, 69317
Actively Recruiting
27
Hopital PONTCHAILLOU CHU de Rennes
Rennes, France, 35000
Actively Recruiting
28
Hôpital Paul Brousse
Val-de-Marne, France, 94800
Actively Recruiting
29
Universitätsklinikum der RWTH Aachen
Aachen, Germany, 52074
Actively Recruiting
30
Charité - Campus Virchow-Klinikum
Berlin, Germany, 13353
Actively Recruiting
31
Hannover Medical School
Hanover, Germany, 30625
Actively Recruiting
32
Universitätsklinikum Tübingen
Tübingen, Germany, 72076
Actively Recruiting
33
Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Actively Recruiting
34
ID Clinic Arkadiusz Pisula
Mysłowice, Poland, 41-400
Withdrawn
35
CCA Hospital Braga
Braga, Portugal, 4710-243
Actively Recruiting
36
Hospital Dr. Nélio Mendonça
Funchal, Portugal, 9000-168
Actively Recruiting
37
Centro Hospitalar de Universitário de Santo António E.P.E
Porto, Portugal, 4099-001
Actively Recruiting
38
Hospital Universitario Virgen del Rocio - PPDS
Seville, Spain, 41018
Actively Recruiting
39
Karolinska Universitetssjukhuset Huddinge
Huddinge, Sweden, 14186
Actively Recruiting
40
Universitätsspital Bern
Bern, Switzerland, 3010
Actively Recruiting
41
King's College Hospital
London, United Kingdom, SE5 9RS
Actively Recruiting
Research Team
T
Takeda Contact
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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