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Evaluating the safety and effectiveness of fazirsiran for liver disease caused by an abnormal protein.

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

Phase 3 Interventional Takeda · NCT05677971

This study is testing if a new drug called fazirsiran can help reduce liver scarring in people with Alpha-1 Antitrypsin Deficiency.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment160 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorTakeda Industry-sponsored
Locations89 sites (Birmingham, Alabama and 88 other locations)
Trial IDNCT05677971 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and efficacy of fazirsiran in reducing liver scarring (fibrosis) in patients with Alpha-1 Antitrypsin Deficiency. Participants will be randomly assigned to receive either fazirsiran or a placebo, with evaluations including liver biopsies and blood biomarkers to measure liver function and scarring. The study will also investigate how the body processes fazirsiran and its effects on liver inflammation and the abnormal Z-AAT protein. The trial is designed to provide comprehensive data on the drug's pharmacodynamics and pharmacokinetics.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with a confirmed diagnosis of Z allele homozygotes (PiZZ) genotype AATD and evidence of moderate to severe liver fibrosis.

Not a fit: Patients with other genotypes such as PiMZ or PiSZ, or those without significant liver fibrosis, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve liver health and quality of life for patients with Alpha-1 Antitrypsin Deficiency.

How similar studies have performed: Previous studies have shown promise in targeting liver fibrosis with similar therapeutic approaches, but this specific treatment is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Birmingham, Alabama and 88 other locations

+39 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Alpha1-Antitrypsin Deficiency
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.