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

• Status: Not yet recruiting
• Trial end date: 2025-09-15
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the effect of setanaxib on biochemical response at Week 52 in participants with primary biliary cholangitis (PBC) and with elevated liver stiffness and intolerance or inadequate response to ursodeoxycholic acid (UDCA).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genkyotex Suisse SA

Criteria

Inclusion Criteria:

1. Male or female participant aged ≥18 years, inclusive at the time of informed consent.

2. Willing and able to give written informed consent and to comply with the requirements of the study.

3. Definite or probable primary biliary cholangitis (PBC) diagnosis as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:

• Documented history of elevated alkaline phsopatase (ALP) levels ≥1.67×upper limit of normal (ULN) of the local reference range.

• Positive antimitochondrial antibodies (AMA) titer or, if AMA negative or in low titer (<1:80), positive PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex]).

• Liver biopsy consistent with PBC.

4. Serum ALP ≥1.67×ULN at Screening.

5. Liver stiffness measured by transient elastography (FibroScan®) of ≥8.8 kilopascals (kPa) at Screening and at Baseline (a minimum of 10 valid readings, with at least a 70% success rate and an interquartile range of ≤30% of the median value, are taken with the results expressed in kilopascals).

6. 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).

7. For participants receiving obeticholic acid (OCA), fenofibrate, or bezafibrate treatment for at least 6 months and stable dose for >3 months prior to Screening.

8. For participants intolerant to OCA, OCA must have been discontinued >3 months prior to Screening.

9. For participants previously treated with bezafibrate or fenofibrate, these agents must have been be discontinued >3 months prior to Screening.

10. 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 "All female participants after menarche unless they are postmenopausal for at least 2 years or are surgically sterile."

• For female participants ≤55 years of age who are considered postmenopausal and who are not on concomitant estrogen replacement therapy, confirmation of postmenopausal status will be required with follicle stimulating hormone (FSH) test results in the postmenopausal range for age at Screening.

• Highly effective contraception is defined as use of 2 barrier methods (eg, female diaphragm and male condoms) or use of at least 1 barrier method in combination with spermicide, an intrauterine device or hormonal contraceptives (eg, implant or oral).

11. Female participants of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline/Randomization before dosing.

12. Male participants with female partners of childbearing potential must be willing to use a condom and require their partner to use an additional form of adequate contraception as approved by the Investigator, such as an established form of hormonal contraceptive, a diaphragm or cervical/vault cap, or intrauterine device. This requirement begins at the time of informed consent and ends 90 days after receiving the last dose of IMP.

13. Male participants must be willing not to donate sperm, and female study participants must be willing not to donate eggs, from Baseline until 90 days after the last dose of IMP.

Exclusion Criteria:

1. A positive pregnancy test or breastfeeding for female participants.

2. 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.

3. 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.

4. Cirrhosis with complications, including history or presence of hepatocellular carcinoma.

5. Total bilirubin >2×ULN. In case of total bilirubin elevation >ULN the Screening serum albumin must be within the reference range.

6. Plasma alanine aminotransferase (ALT) >3×ULN and/or aspartate aminotransferase (AST) >3×ULN.

7. International normalized ratio (INR) >1.2 unless participant is on anticoagulant therapy.

8. Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2, as calculated by the central laboratory using the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation.

9. Thyroid-stimulating hormone >ULN at Screening.

10. 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).

11. Medical conditions that could cause nonhepatic increases in ALP (eg, Paget's disease).

12. Known history of human immunodeficiency virus (HIV) infection.

13. Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines (as judged by the Investigator).

14. Positive urine drug screen (if not due to prescriptional use of a concomitant medication, as confirmed by the Investigator) at Screening.

15. Participants receiving prohibited medications within 3 months of Screening Visit 1 including oral and systemic corticosteroids, colchicine, mycophenolate mofetil, azathioprine, methotrexate, sulfasalazine, leflunomide, cyclophosphamide, valproate, isoniazid, or nitrofurantoin. Any biologic agent within 12 weeks or 5 half-lives prior to Screening, whichever is longer. In the case of rituximab, use within 168 days (24 weeks) of Screening is exclusionary.

16. 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.

17. Evidence of any of the following cardiac conduction abnormalities: A QTc Fredericia 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.

18. Treatment or planned treatment, with a pacemaker, implanted cardioverter-defibrillator, or other implanted electronic device.

19. 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.

20. The occurrence of any acute infection requiring systemic antibiotic therapy within the 2 weeks prior to Screening Visit 1.

21. A history of bone marrow disorder including aplastic anemia, or any current marked anemia defined as hemoglobin <10.0 g/dL.

22. Prior treatment with setanaxib or participation in a previous setanaxib clinical trial.

23. Unstable cardiovascular disease.

24. 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.

25. 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.