CS0159 in Chinese Patients With PSC (Primary Sclerosing Cholangitis)

Study Overview
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Brief Summary
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A phase II Study of CS0159 in Chinese patients with PSC(Primary Sclerosing Cholangitis)

Detailed Description
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A phase II study to evaluate safety, tolerability and efficacy, of CS0159 in patients with Primary Sclerosing Cholangitis, this is a multicenter, randomized, 12-weeks double-blind, placebo-controlled, and 40-week open study.

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

Conditions
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Primary Sclerosing Cholangitis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age≥18 or age≤75 years when sign ICF Within the last year, have a clinical diagnosis of PSC with a consistent magnetic resonance cholangiopancreatography (MRCP) orendoscopic retrograde cholangiopancreatography (ERCP) Prcutaneous Transhepatic Cholangiography(PTC) showing sclerosing cholangitis ALP≥1.67×ULN also≤10×ULN and TBil≤3 mg/dL during screen Taken UDCA(≤25mg/kg/d)≥6 months before randomization and stable does≥ 3 months, or not used UDCA≥3 months before randomization For subject with a history of IBD, The subject was not hospitalized for IBD three months prior to screening, also, Patients with Crohn's Disease (CD),Must be in remission, CDAI<150 or CDAI of score ≤4 Patients with(Ulcerative Colitis)UC,Must be in remission or only mild activity,Some Mayo scores range from 0 to 4 Be able to understand and Comply with the study protocol sign a written informed consent form(ICF)voluntarily Exclusion Criteria, Presence of documented secondary sclerosing cholangitis when screening,or direct evidence IgG4 related sclerosing cholangitis or serum IgG4 ≥ 4 ×ULN Small duct PSC ALT or AST>5×ULN Taken( ObeticholicAcid) OCA within 3 months before randomization Acute cholangitis was suspected or confirmed within 3 months prior to randomization, Including acute cholangitis being treated during screening Presence of percutaneous drain or bile duct stent at the time of screening or during the study Known within the other hepatobiliary diseases or medical history,including but not limited to: Active hepatitis B Virus or hepatitis C virus infection, PBC, Complete biliary obstruction, acute cholecystitis orgall-stone,Autoimmune hepatitis or overlap with other autoimmune liver diseases, Alcoholic Hepatitis, NASH, Suspected or confirmed primary liver cancer,cholangiocarcinoma Child-Pugh patients with grade B or C cirrhosis,Present complications related to cirrhosis or End-stage liver disease ,Including history of liver transplantation Preparing for liver transplantation (Model for End-Stage Liver Disease)MELD≥15，Portal hypertension complications,Complications of cirrhosis Hepatitis B surface antigen positive or Hepatitis C antibody positive during screening, (Human Immunodificidncy Virus Antibodies) HIVAb positive, or (Treponema PallidumAntibodies)TPAb was positive Cr(Creatinine)≥1.5×ULN also Cr(Creatinine)clearance rate<60 mL/min PLT(Platelet)<100×10^9/L INR(international normalized ratio)>1.3 ALB<3.5g/dL Severe pruritus may require systemic medication Within 2 months prior to randomization Arrhythmia,male QTc≥450 ms,female QTc≥470 ms, during screening A disease that interferes with the absorption, distribution, metabolism, or excretion of a test drug,such as moderate to severe activity IBD patient, Previous gastric bypass surgery Moderate or intense inhibition of CYP3A4 was performed during 14 days prior to randomization and throughout the trial Preparation or inducer The presence of diseases that may cause non-hepatic elevation of ALP (e.g. Paget's disease) or may cause it Diseases with a life expectancy of less than 2 years History of malignancy within the past 5 years prior to randomization Used immunosuppressor Budesonide and other systemic glucocorticoids within 1 month prior to randomization and throughout the clinical study period Used Fenofibrate or whatever Tabates drug, Hepatotoxic, hepatic, protector, choleretic drug within 1 month prior to randomization and throughout the clinical study period Interleukin or other cytokines were used 12 months before randomization and throughout the trial Or antibodies to chemokines or immunotherapy Drug and/or alcohol abuse within the first six months of randomization Poor blood pressure control,systolic pressure>160 mmHg or dpb >100 mmHg Poor blood sugar control,Glycated hemoglobin>9.0% Females who are pregnant or plan to pregnant,Fertile but refusing to sign informed consent, or breastfeed Participated any other study within 30 days prior randomization,and received other experimental medications therapy It is unsuitable to participate for the study or has other diseases 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: CS0159 2mg<br>* Oral QD<br>Drug: Placebo<br>* Oral QD<br>|
| Experimental: 4mg CS0159<br>QD for 12 weeks | Drug: CS0159 2mg<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 placebo, 2mg and 4mg group | Baseline to 12 weeks | 
| relative changes from baseline in ALP at week 12 | The reduction of percentage of ALP level from baseline to 12 weeks | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absulute changes from baseline in ALP at week 12 | The reduction of ALP level from baseline to 12 weeks | Baseline to 12 weeks | 
| ALP and TBil changes | Compared with placebo, ALP< 1.67 ULN, (total bilirubin) TBil ≤ULN | Baseline to 12 weeks | 
| TBA changes | BA change from baseline | from basline to 12 weeks, and to 40 weeks | 
| Pruritus incidence | changes from baseline in the study period | from basline to 40 weeks |