A Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Liver Stiffness

Exclusion Criteria

• •A positive pregnancy test or breastfeeding for female participants.
• •Any historical or current hepatic decompensation event defined as variceal/portal hypertension bleed and/or hepatic encephalopathy, spontaneous bacterial peritonitis, ascites requiring treatment, or liver transplantation list inclusion.
• •History of liver transplantation, current placement on a liver transplant list or current model for end stage liver disease (MELD) score of ≥12 unless the participant is on anticoagulant therapy, or a Child-Pugh Score of ≥6.
• •Cirrhosis with complications, including history or presence of hepatocellular carcinoma.
• •Total bilirubin \>2×ULN. In case of total bilirubin elevation \>ULN the Screening serum albumin must be within the reference range.
• •Plasma alanine aminotransferase (ALT) \>3×ULN and/or aspartate aminotransferase (AST) \>3×ULN.
• •International normalized ratio (INR) \>1.2 unless participant is on anticoagulant therapy. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for participants who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the participant may be eligible for the study.
• •Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m\^2, as calculated by the central laboratory using the chronic kidney disease-epidemiology collaboration (CKD- EPI) equation.
• •Thyroid-stimulating hormone \>ULN at Screening. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for participants who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the participant may be eligible for the study.
• •Competing etiology for liver disease (eg, hepatitis C \[unless effectively cured of hepatitis C, with a sustained virologic response for at least 6 months prior to Screening\], active hepatitis B \[HBsAg positive\], nonalcoholic steatohepatitis \[NASH\], alcoholic liver disease, autoimmune hepatitis, autoimmune hepatitis-PBC overlap syndrome, primary sclerosing cholangitis, Gilbert's Syndrome).
• •Medical conditions that could cause nonhepatic increases in ALP (eg, Paget's disease).
• •Known history of human immunodeficiency virus (HIV) infection.
• •Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines (as judged by the Investigator).
• •Positive urine drug screen (if not due to prescriptional use of a concomitant medication, as confirmed by the Investigator) at Screening. Participants on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening Visit 1 may be included in the study. Medicinal cannabis and cannabidiol products are not exclusionary and may be allowed if the prescription and diagnosis are reviewed and approved by the Investigator.
• •Participants receiving prohibited medications within 3 months of Screening Visit 1.
• •Treatment with any investigational agent within 12 weeks of Screening Visit 1 or 5 half-lives of the IMP (if known) (whichever is longer) or current enrollment in an interventional clinical trial.
• •Evidence of any of the following cardiac conduction abnormalities: A QTc Fridericia interval \>450 milliseconds for males or \>470 milliseconds for females, as calculated by the central reader. Participants with a second- or third-degree atrioventricular block are to be excluded.
• •History of a malignancy within 5 years of Screening with the following exceptions:
• •* Adequately treated carcinoma in situ of the cervix.
• •* Adequately treated basal or squamous cell cancer or other localized nonmelanoma skin cancer.
• •The occurrence of any acute infection requiring systemic antibiotic therapy within the 2 weeks prior to Screening Visit 1.
• •A history of bone marrow disorder including aplastic anemia, or any current marked anemia defined as hemoglobin \<10.0 g/dL.
• •Prior treatment with setanaxib or participation in a previous setanaxib clinical trial.
• •Unstable cardiovascular disease.
• •Presence of any laboratory abnormality or condition that, in the opinion of the Investigator, could interfere with or compromise a participant's treatment, assessment, or compliance with the protocol and/or study procedures.
• •Any other condition which, in the opinion of the Investigator, constitutes a risk or contraindication for the participation of the participant in the study, or that could interfere with the study objectives, conduct, or evaluation.
• •Hypersensitivity or intolerance to setanaxib or to any of its excipients or placebo compounds.