CS0159 in Chinese Patients With PBC (Primary Biliary Cholangitis)

Study Overview
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Brief Summary
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A phase II study to evaluate safety, tolerability and efficacy of CS0159 in patients with PBC (Primary Biliary Cholangitis).

Detailed Description
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This is a phase II study to evaluate safety, tolerability and efficacy of CS0159 in patients with PBC (Primary Biliary Cholangitis). The study has been designed to have two parts, the first part of the study will be double-blinded for 12 weeks. The second part of the study will be an open-label trail lasting 40 weeks.

Official Title
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A Phase II Study to Evaluate Safety, Tolerability and Efficacy, of CS0159 in Patients Subjects With PBC (Primary Biliary Cholangitis), Multicenter, Randomized 12-week, Double-blind, Placebo-controlled, and 40-weeks Open Study

Conditions
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Primary Biliary Cholangitis (PBC)

Intervention / Treatment
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* Drug: 2mg CS0159
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: When signing ICF age≥18 years≤75 years, male or female Meets the diagnostic criteria of PBC, such as elevation ALP, positive AMA or AMA-M2, If negative for AMA, positive for PBC specific antibody and Liver biopsy meeting PBC criteria six months before screening 1.67 × ULN≤ ALP≤ 10 × ULN and TBil ≤ 2 mg/dL UDCA≥6 months before randomization and a stable dose (no less than 13-15 mg/kg/d in principle) ≥3 months after the efficacy was poor (meeting inclusion criteria 3), or UDCA was not tolerated, and stop taking UDCA (no UDCA use for ≥3 months before randomization) Understand the study content, comply with the study protocol, and sign the ICF voluntarily - Exclusion Criteria: ALT or AST>5×ULN； OCA(Obercholic acid) in the 3 months prior to randomization Known concomitant hepatobiliary disease or history Significant hepatic impairment as defined by Child-Pugh classification of B or C, history of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥15. Active Hepatitis B or C virus (HCV, HBV) infection (creatinine, Cr）≥1.5×ULN and Cr clearance rate <60 mL/min platelet<100×10^9/L； INR>1.3 ALB<3.5 g/dL Severe pruritus or systemic medication was required within 2 months prior to randomization Arrhythmia, Or during screening the QTc interval was ≥450 ms for male and 470 ms for female History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the large intestine, eg, inflammatory bowel disease, prior or planned (during the study period) bariatric surgery (such as gastroplasty, roux-en-Y gastric bypass). Concomitant use of medications, food, and drinks that are strong or moderate CYP3A4 inhibitors or inducers within 14 days prior to the first dose of study drug and throughout the study duration. Diseases that may cause non-hepatic elevation of ALP (such as Paget's disease) or may result in a life expectancy of less than 2 years A history of malignant tumor within 5 years prior to randomization The following medications were administered one month prior to randomization and throughout the clinical study period: azathioprine, colchicine, cyclosporine A, methotrexate, mycophenolate mofetil, pentoxifylline, fenofibrate or other fibrates, budesonide and other systemic corticosteroids; hepatotoxic drugs; hepatic protectors; choleretic agents. The administration of interleukin or other cytokine antibodies, as well as chemical factors or immunotherapy, was prohibited from 12 months prior to randomization throughout the clinical study period Substance abuse or alcoholism from 6 months prior to randomization throughout the entire clinical study period Poor blood pressure control is indicated by a systolic pressure greater than 160 mmHg or diastolic pressure greater than 100 mmHg during screening Poor blood glucose control, that is, HBA1c >9.0% at screening Pregnancy, planned pregnancy, lactation Use of other investigational drugs within 3 months Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study, as judged by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2mg CS0159<br>QD for 12 weeks | Drug: 2mg CS0159<br>* Oral QD<br>Drug: Placebo<br>* Oral QD<br>|
| Experimental: 4mg CS0159<br>QD for 12 weeks | Drug: 2mg CS0159<br>* Oral QD<br>|
| Experimental: Placebo<br>QD for 12 weeks | Drug: Placebo<br>* Oral QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE incidence | AE incidence in three arms | baseline to 12 weeks | 
| relative changes from baseline in ALP at week 12 | Compared with placebo ,Percentage change of CS0159 to ALP relative to baseline | baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absulute changes from baseline in ALP at week 12 | Compared with placebo, CS0159 changes in serum ALP relative to baseline | baseline to 12 weeks | 
| ALP and TBil | Compared with placebo, the rate of subjects to achive the lelve of ALP< 1.67 ULN and (total bilirubin) TBil ≤ULN | baseline to 12 weeks | 
| Pruritus | the changes from baseline in Pruritus to week 40 | from basline to 40 weeks | 
| Liver function: ALT, AST, ALB, LDL, TBA, GGT, TC, TG | The reduction of ALT, AST, ALB, LDL, TBA, GGT, TC, and TG from baseline to week 40. | from baseline to week 40. |