Testing Fazirsiran against a placebo for alpha1-antitrypsin deficiency
Official title: 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
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
- 2 groups
- Sites in Vancouver, Halifax and 1 more city
- Recruiting
Interventions
- Medication
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.
- Other intervention
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.
Canadian Sites (3)
3 of 3 recruiting
- Recruiting
GI Research Institute
Vancouver, British Columbia
- Recruiting
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia
- Recruiting
Inspiration Research Limited
Toronto, Ontario
Eligibility Criteria
See who this study is looking for35 criteria
The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.
Inclusion
- +The participant, of any sex, is aged 18 to 75 years, inclusive.
- +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 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 screeningScreeningThe checks done before joining, to see whether a study fits.Read more →. PiMZ or PiSZ genotypes are not permitted.
- +The participant's liver biopsy core sample collected should meet the requirements of the protocolProtocolThe detailed plan a study must follow.Read more →.
- +The participant has evidence of METAVIR stage F2, F3, or F4 liver fibrosis, evaluated by a centrally read baselineBaselineYour starting measurements, taken before treatment begins.Read more → 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 enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more → 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 randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →.
- +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 CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →
- +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 eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more →.
- +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.
Exclusion
- −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 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 enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more → date. For certain participants, an EGD will be required at screeningScreeningThe checks done before joining, to see whether a study fits.Read more → 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 eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more →.
- −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.
In plain language
Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.
What this study is
This study is testing a treatment for a condition.
Phase 3Phase 3A large study comparing a treatment against the current standard.Read more → — a large study comparing this against the current standard, usually across many hospitals.
From the trial registry
Built from these fields:
- designModule.designInfo.primaryPurpose
- designModule.phases
Who receives what
There are 2 groups in this study.
Group A receives Fazirsiran Injection.
Registry label: A: Fazirsiran
Group B, the placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group, receives Placebo.
Registry label: B: Placebo
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].label
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
How the study is run
Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.
You, the study team, the people giving the treatment, and the people analysing the results would all be kept unaware of which group you are in until the study ends.
From the trial registry
Built from these fields:
- designModule.designInfo.allocation
- designModule.designInfo.maskingInfo.masking
Is there a placebo?
One group receives a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → — a dummy treatment with no active medicine in it.
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
Who the study is looking for
The study lists an age range of 18 years to 75 years.
The study is open to people of any sex.
The study does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
These are the criteria the study lists. Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part.
From the trial registry
Built from these fields:
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How big and how long
The study aims to enrol about 160 people.
The study is currently expected to finish around December 2031.
The main measurement is taken over: BaselineBaselineYour starting measurements, taken before treatment begins.Read more →, Week 106.
From the trial registry
Built from these fields:
- designModule.enrollmentInfo.count
- statusModule.completionDateStruct.date
- outcomesModule.primaryOutcomes[].timeFrame
What the study measures
Reduction From BaselineBaselineYour starting measurements, taken before treatment begins.Read more → 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.
From the trial registry
Built from these fields:
- outcomesModule.primaryOutcomes[].measure
- outcomesModule.primaryOutcomes[].timeFrame
Source: NCT05677971 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.
Not medical advice. What do these terms mean?
What is being tested — in plain terms
About Fazirsiran InjectionDrug
Participants will receive fazirsiran 200 mg/ml SC injection on Day 1, at Week 4, and Q12 W thereafter up to Week 196.
From the trial registry — its own words, unedited.
What a drug is here: A medicine — a chemical or small-molecule treatment — given as the thing being studied.
Read the full explanation → · in clinical review
About PlaceboOther
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.
From the trial registry — its own words, unedited.
What a other is here: An intervention the registry did not place in another category.
Read the full explanation → · in clinical review
Common questions
Answered from this trial’s registry record. Where the record doesn’t say, these answers say so rather than filling the gap.
Am I eligible for this trial?
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part. Concord cannot make that determination, and neither can any tool that has not examined you.
What the study lists: an age range of 18 years to 75 years.
The full inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → and exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → are published on this page, exactly as the study team wrote them.
The useful next step is to bring this trial to your doctor. Answering a few questions first gives them something concrete to review.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.eligibilityCriteria
Is there a placebo?
Yes. This study includes a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group — a dummy treatment with no active medicine in it.
From the trial registry
- armsInterventionsModule.armGroups[].type
Would I know which treatment I am getting?
You, the study team, the people giving the treatment, and the people analysing the results would all be kept unaware of which group you are in until the study ends.
Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.
From the trial registry
- designModule.designInfo.maskingInfo.masking
- designModule.designInfo.allocation
Who can join?
The study lists an age range of 18 years to 75 years.
It is open to people of any sex.
It does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can confirm whether a particular person can take part.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How long would this take?
The study's main measurement is taken over: BaselineBaselineYour starting measurements, taken before treatment begins.Read more →, Week 106.
The study as a whole is currently expected to finish around 2031-12-12.
How long any one person takes part can differ from the study length. The study team can tell you what the schedule looks like in practice.
From the trial registry
- outcomesModule.primaryOutcomes[].timeFrame
- statusModule.completionDateStruct.date
How many people are taking part?
The study aims to enrol about 160 people.
From the trial registry
- designModule.enrollmentInfo.count
Where is this happening?
This study lists 7 locations, including: Vancouver, British Columbia, Canada; Halifax, Nova Scotia, Canada; Toronto, Ontario, Canada; Ann Arbor, Michigan, United States; Novi, Michigan, United States; Rochester, Minnesota, United States, and 1 more.
Sites can open and close during a study, so confirm with the team before travelling.
From the trial registry
- trial_locations
About This Trial
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.
Other Sites (6)
University of Michigan Hospital
Ann Arbor, Michigan, United States
Henry Ford Medical Center - Columbus
Novi, Michigan, United States
Mayo Clinic - PPDS
Rochester, Minnesota, United States
NYU Langone Health
New York, New York, United States
Morgan Stanley Childrens Hospital of New York Presbyterian (CHONY) - PIN
New York, New York, United States
Columbia University Irving Medical Center
New York, New York, United States
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See if this trial could fit youThis page is for informational purposes only and does not constitute medical advice. Clinical trial eligibility can only be determined by the trial site after proper screening. Trial information is sourced from ClinicalTrials.gov and may not reflect the most current status. Always consult your healthcare provider before making decisions about clinical trial participation.