A Randomized Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Fazirsiranin the Treatment of Alpha-1 Antitrypsin Deficiency-Associated Liver Disease with METAVIR Stage F2 to F4 Fibrosis

Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    Alpha-1 Antitrypsin Deficiency-associated Liver Disease
  • Age: Between 18 Year(s) - 75 Year(s)
  • Gender: Male or Female
  • Other Inclusion Criteria:
    1. The participant must have a diagnosis of the PiZZ genotype AATD.
    2. Any participant who is taking statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or beta-1 selective adrenergic receptor inhibitors must have been receiving a stable dose of these medications for at least 2 months before randomization.
    3. An adult participant must have a body mass index (BMI) between 18.0 and 39.0 kg/m2, inclusive.
    4. The participant is a nonsmoker (defined as does not smoke cigarettes daily for at least 12 months before screening) with current nonsmoking status confirmed by urine cotinine at screening.
    5. If the participant was being treated with any respiratory medications including inhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, or low-dose systemic corticosteroids (prednisone =10 mg/d or its equivalent), the doses of their medications had remained unchanged for at least 14 days before screening.
    6. The participant must have suitable venous access for blood sampling.
    7. A person of childbearing potential (POCBP) must have a negative serum pregnancy test at screening and urine pregnancy test on Day 1 before dosing.
    8. The participant must use highly effective contraception for the entire duration of the study and for 6 months after the last dose of study medication. The participant must not donate sperm for at least 6 months after the last dose of study medication.

You may not be eligible for this study if the following are true:

    1. The participant has a history of liver decompensating events.
    2. The participant has a history of the presence of medium or large varices or varices with red wale signs based on a previous EGD within 6 months before the estimated enrollment date.
    3. The participant has portal vein thrombosis.
    4. The participant has a prior transjugular portosystemic shunt procedure.
    5. The participant has evidence of other forms of chronic liver diseases, including viral hepatitis B or C, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson disease, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary diversion, or autoimmune hepatitis.
    6. 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.
    7. The participant has a recent lower respiratory tract infection, such as pneumonia, within the last 6 months before screening.
    8. The participant has a history of frequent PEs (greater than or equal to 2 moderate or severe exacerbations within 52 weeks before screening).
    9. The participant is experiencing a PE at the time of screening (participant may be rescreened after the clinical resolution of an exacerbation).
    10. The participant is receiving long-term around-the-clock oxygen (O2) supplementation or supplemental O2 with continuous positive airway pressure (CPAP), or bi-level positive airway pressure (BiPAP) for acute respiratory failure.
    11. The participant has a HIV infection as shown by the presence of anti-HIV antibody (seropositive).
    12. The participant has uncontrolled hypertension.
    13. The participant has a history of torsades de pointes, ventricular rhythm disturbances (eg, ventricular tachycardia), heart block (excluding first-degree block, being pulse rate (PR) interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG.
    14. The participant has symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease, transient ischemic attack or cerebrovascular accident within 6 months before screening.
    15. The participant has a history of major surgery within 3 months before screening (or longer, at the discretion of the investigator).
    16. The participant has a history of organ transplant.
    17. The participant has a history of more than moderate alcohol consumption within 12 months before the screening visit (ie, more than 1 unit of alcohol per day for women and more than 2 units per day for men).
    18. 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.
    19. The participant has previously been treated with fazirsiran or any other RNAi for AATD-LD.
    20. The participant has a history of hypersensitivity or allergies with any associated excipients of fazirsiran.
    21. The participant has received an investigational agent or device within 30 days, or 5 half-lives, whichever is longer, before study medication dosing or is currently participating in an investigational study involving a therapeutic intervention. Participants receiving AAT augmentation therapy as part of a postmarketing study or other access program for approved therapies are acceptable.
    22. The participant has donated =500 mL blood within 1 month of study treatment administration.
    23. The participant has a history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism), within 6 months before screening; or is taking chronic anticoagulants, aspirin, or nonsteroidal anti-inflammatory medications.
    24. This participant is unable to return for all scheduled study visits.
    25. The participant has known or suspected COVID-19 by the investigator within the past 2 months before screening.
    26. The participant is an employee of the sponsor or study site or immediate family member (eg, spouse, parent, child, sibling) of an employee of the sponsor or study site.
    27. The participant is pregnant or breastfeeding or intends to become pregnant before participating in this study, during the study, or within 6 months after last dose of the study drug; or intending to donate ova during such time period.

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