Takeda is launching a clinical trial to determine the safety and capacity of fazirsiran in reducing liver scarring in patients with alpha-1 antitrypsin deficiency (AATD).
Starting January 24, the placebo-controlled phase 3 study will enroll 160 participants with the PiZZ genotype and evidence of METAVIR stage F2, F3, or F4 liver fibrosis. Participants will be randomized in a double-blind manner into 2 groups.
The treatment group will receive fazirsiran 200 mg/mL subcutaneous injection on day 1, at week 4, and every 12 weeks thereafter up to week 196; the placebo group will receive a placebo subcutaneous injection on day 1, at week 4, and every 12 weeks thereafter up to week 196.
Participants must be aged 18 to 75 years, nonsmokers, and have a body mass index between 18.0 and 39.0 kg/m2. The diagnosis of hepatocellular carcinoma must be ruled out in all participants. Furthermore, specific requirements apply to participant’s liver biopsy core sample and pulmonary status.
Read about AATD therapies
The primary outcome measure of the study is the reduction from baseline of at least 1 stage of histologic fibrosis (METAVIR staging) in the centrally read liver biopsy at week 106 in patients with stage F2 or F3 fibrosis.
In addition to the primary goal, the study aims to understand the role of fazirsiran in attenuating disease worsening in the liver, reducing other liver injury, such as inflammation, and decreasing the abnormal Z-AAT protein in the liver, and to investigate pharmacokinetics and pharmacodynamics. Therefore, the study protocol includes 15 secondary outcome measures.
Excluded from the study are: patients who have previously been treated with fazirsiran or any other RNA interference therapy; patients with a history of liver decompensating events; patients with a history of malignancy within the last 5 years (exceptions might apply); patients with a history of the presence of medium or large varices or varices with red wale signs; patients with a history of drug abuse within 1 year before the screening visit or positive urine drug screen at screening; patients with prior transjugular portosystemic shunt procedure, evidence of other forms of chronic liver diseases, or portal vein thrombosis.
Also excluded are those with alanine transaminase or aspartate transaminase levels higher than 250 U/L, platelet count lower than 60.000/mm3, albumin levels of 2.8 g/dL or below, or an international normalized ratio equal to or above 1.7, as well as those expected to have severe and unavoidable high-level exposure to inhaled pulmonary toxins during the study.
The trial is expected to last 5 years and the estimated primary completion date is February 28, 2026.
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. ClinicalTrials.gov. January 10, 2023. Updated January 13, 2023. Accessed January 19, 2023.