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

Inclusion Criteria

• Male or female participant aged ≥18 years, inclusive at the time of informed consent.
• Willing and able to give written informed consent and to comply with the requirements of the study.
• Definite or probable PBC diagnosis as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:
• Documented history of elevated ALP levels ≥1.67×ULN of the local reference range.
• Documented history of positive antimitochondrial antibodies (AMA) titer or positive PBC-specific antibodies (anti-GP210 or anti-SP100 or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex]).
• Historical liver biopsy consistent with PBC.
• Serum ALP ≥1.67×ULN at Screening.
• Liver stiffness measured by transient elastography (FibroScan®) of ≥8.8 kilopascals (kPa) and an interquartile range over median ratio (IQR/med) of ≤30% at Screening, are taken with the results expressed in kilopascals).
• Ursodeoxycholic acid (UDCA) prescriptional dose use for the past 6 months (at a stable dose for >3 months prior to Screening) OR intolerant to UDCA (last dose of UDCA >3 months prior to Screening). Intolerance to UDCA is defined as participants unable to tolerate the full-labelled dose of UDCA in PBC (13-15 mg/kg) due to frequently reported gastrointestinal symptoms such as diarrhea and abdominal pain.
• For participants receiving obeticholic acid (OCA), fenofibrate, or bezafibrate treatment for at least 6 months and stable dose for >3 months prior to Screening.
• For participants intolerant to OCA, OCA must have been discontinued >3 months prior to Screening.
• For participants previously treated with bezafibrate or fenofibrate, and these agents were discontinued prior to screening, they must have been discontinued >3 months prior to Screening.
• Female participants of childbearing potential must use a highly effective method of contraception to prevent pregnancy for ≥4 weeks before Randomization and must agree to continue strict contraception up to 90 days after the last dose of investigational medicinal product (IMP).
• For the purposes of this trial, women of childbearing potential are defined as "Fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy."
• Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. In female participants who are not using hormonal contraception or hormonal replacement therapy but with suspected menopause and less than 12 months of amenorrhea, a high follicle stimulating hormone (FSH) level in the postmenopausal range will be required at Screening to confirm a postmenopausal state. Confirmation with more than one FSH measurement is required.
• Highly effective contraception is defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. These methods are:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
• Intrauterine device
• Intrauterine hormone-releasing system
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence (refraining from heterosexual intercourse during the entire period of risk associate with the study treatments). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
• Female participants of childbearing potential must