Fazirsiran for Liver Disease and Scarring in Alpha-1 Antitrypsin Deficiency
This study is testing a drug called fazirsiran to see if it can help people with liver disease and scarring (fibrosis) caused by an abnormal version of alpha-1 antitrypsin protein (AATD). Researchers want to know if fazirsiran can reduce liver scarring compared to a placebo (an inactive substance like sterile saline). They will also look at how fazirsiran affects the body, reduces liver injury and the abnormal protein, and check for side effects. You may be able to join if you are 18 to 75 years old and have a specific genetic diagnosis of AATD (PiZZ genotype). The main goal is to see if fazirsiran can reduce liver scarring by at least one stage after about two years.
- Study design
- This is an interventional study with a planned enrollment of 160 participants. Participants will receive either fazirsiran or a placebo.
- What's involved
- Participants will receive injections on Day 1, at Week 4, and then every 12 weeks up to Week 196. Liver biopsies will be taken at baseline and Week 106.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint is measured at Week 106, which is about two years after starting treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05677971
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
Recruiting
PHASE3Ages 18–75InterventionalTreatmentTakeda
~160 participants
Updated 2026-05-13 on ClinicalTrials.gov
What's tested:Fazirsiran InjectionPlacebo
At a glance
Recruiting sites
81 of 89 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
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
Measured over Baseline, Week 106
Conditions
Where it's being run
89 sites across 42 statesFrance6
United Kingdom6
California5
Germany5
Austria4
Italy4
Spain4
Arizona3
Study leadership
- Study Director · STUDY_DIRECTOR · Takeda
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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.
What this trial measures
- 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 FibrosisBaseline, Week 106
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.