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
| NCT ID | NCT05677971 |
| Status | Recruiting |
| Phase | Phase 3 |
| Sponsor | Takeda |
| Condition | Alpha1-Antitrypsin Deficiency |
| Study Type | INTERVENTIONAL |
| Enrollment | 160 participants |
| Start Date | 2023-03-06 |
| Primary Completion | 2029-01-17 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 3 trials are large pivotal studies comparing the treatment to current standard of care or placebo. Your participation directly contributes to the evidence needed for regulatory approval.
This trial targets 160 participants in total. It began in 2023-03-06 with a primary completion date of 2029-01-17.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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.
Eligibility 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.
Contact & Investigator
Study Director
STUDY DIRECTOR
Takeda
Frequently Asked Questions
Who can join the NCT05677971 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 75 Years, studying Alpha1-Antitrypsin Deficiency. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05677971 trial and what does that mean for participants?
Phase 3 trials are large-scale studies comparing the new treatment to existing standards of care or a placebo. They provide the evidence needed for regulatory approval. This trial targets 160 participants.
Is NCT05677971 currently recruiting?
Yes, NCT05677971 is actively recruiting participants. Contact the research team at medinfoUS@takeda.com for enrollment information.
Where is the NCT05677971 trial being conducted?
This trial is being conducted at Birmingham, United States, Phoenix, United States, Phoenix, United States, Tucson, United States and 11 additional locations.
Who is sponsoring the NCT05677971 clinical trial?
NCT05677971 is sponsored by Takeda. The principal investigator is Study Director at Takeda. The trial plans to enroll 160 participants.