Primary Biliary Cholangitis (PBC) and Elevated Liver Stiffness MedDRA version: 21.0 Level: PT Classification code 10080429 Term: Primary biliary cholangitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
Genkyotex Suisse SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient 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 PBC diagnosis as demonstrated by the presence of =2 of the following 3 diagnostic factors: a. Documented history of elevated ALP levels =1.67×ULN of the local reference range b. Positive AMA titer or, if AMA negative or in low titer (3 months prior to Screening) OR intolerant to UDCA (last dose of UDCA >3 months prior to Screening). 7. For patients receiving OCA, fenofibrate, or bezafibrate treatment for at least 6 months and stable dose for >3 months prior to Screening. 8. For patients intolerant to OCA, OCA must have been discontinued >3 months prior to Screening. 9. For patients previously treated with bezafibrate or fenofibrate, these agents must have been be discontinued >3 months prior to Screening. 10. Female patients 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 IMP. a. For the purposes of this trial, women of childbearing potential are defined as “All female patients after menarche unless they are postmenopausal for at least 2 years or are surgically sterile.” b. For female patients =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. c. 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 patients 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 patients 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 patients must be wi
Exclusion criteria
Exclusion criteria: 1. A positive pregnancy test or breastfeeding for female patients. 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 MELD score of =12 unless the patient 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. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for patients who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the patient may be eligible for the study. 6. Plasma ALT >3×ULN and/or AST >3×ULN. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for patients who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the patient may be eligible for the study. 7. INR >1.2 unless patient is on anticoagulant therapy. 8. Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2, 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 HIV infection. If the anti-HIV antibody test is positive, HIV RNA negativity has to be confirmed by the central laboratory. 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. Patients receiving prohibited medications within 3 months of Screening Visit 1 including oral and systemic corticosteroids (see Section 6.6 for exceptions), 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. See the complete list of prohibited medications in Section 6.6. 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 mi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of setanaxib on biochemical response at Week 52 in patients with PBC and with elevated liver stiffness and intolerance or inadequate response to ursodeoxycholic acid (UDCA);Secondary Objective: - To evaluate the effect of setanaxib on liver stiffness at Week 52 - To evaluate the effect of setanaxib on fatigue at Week 52 - To evaluate the effect of setanaxib on pruritus at Week 52 - To evaluate the safety and tolerability of setanaxib over a 52 week treatment period - To further evaluate the safety and tolerability of setanaxib in patients with PBC and with elevated liver stiffness and intolerance or inadequate response to UDCA (Extension phase);Primary end point(s): Proportion of patients achieving a biochemical response at Week 52, defined as: - Alkaline phosphatase (ALP) reduction to <1.67×upper limit of normal (ULN) and - ALP reduction of =15% from Baseline and - Total bilirubin =1×ULN ;Timepoint(s) of evaluation of this end point: Week-52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in liver stiffness at Week 52 compared to Baseline, as assessed by transient elastography (FibroScan®) - Change in fatigue at Week 52 compared to Baseline, as assessed by the PBC-40 item questionnaire (PBC 40) fatigue domain and the fatigue domain of the Patient Reported Outcomes Measurement Information System (PROMIS) 29 questionnaire - Change in pruritus at Week 52 compared to Baseline, as assessed by the PBC-40 itch domain, 5 D itch scale, and Pruritus Visual Analogue Scale (VAS) in patients with pruritus at Baseline - Adverse events (AEs). Monitoring for AEs at all visits. - AEs of special interest (AESIs): Drug induced liver injury (DILI) Anemia Hypothyroidism - Laboratory tests: Hematology Biochemistry Urinalysis Thyroid function - Vital signs - 12-lead electrocardiograms (ECGs): clinically significant abnormalities ;Timepoint(s) of evaluation of this end point: Week-52 | — |
Countries
Australia, Austria, Belgium, Canada, Czechia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactBenedicte Moal Rowland
PRA Health Sciences
Outcome results
None listed