Primary Sclerosing Cholangitis
Conditions
Brief summary
A phase II Study of CS0159 in Chinese patients with PSC(Primary Sclerosing Cholangitis)
Detailed description
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.
Interventions
DRUGCS0159
Oral QD
Sponsors
Cascade Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female age≥18 or age≤75 years when sign ICF 2. 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 3. 1.50×ULN≤ALP≤10×ULN, and TBil≤3×ULN during screen 4. Taken UDCA(≤25mg/kg/d)≥6 months before randomization and stable does≥ 3 months, or not used UDCA≥3 months before randomization 5. For subject with a history of IBD 1. Patients with Crohn's Disease (CD),Must be in remission, CDAI\<150 or CDAI of score ≤4 2. Patients with(Ulcerative Colitis)UC,Must be in remission or only mild activity,Some Mayo scores range from 0 to 4 6. Be able to understand and Comply with the study protocol sign a written informed consent form(ICF)voluntarily
Exclusion criteria
, 1. Presence of documented secondary sclerosing cholangitis when screening,or direct evidence IgG4 related sclerosing cholangitis or serum IgG4 ≥ 4 ×ULN 2. Small duct PSC 3. ALT or AST\>5×ULN 4. Taken( ObeticholicAcid) OCA within 3 months before randomization 5. Acute cholangitis was suspected or confirmed within 3 months prior to randomization, Including acute cholangitis being treated during screening 6. Presence of percutaneous drain or bile duct stent at the time of screening or during the study 7. Known concurrent comorbidities with other hepatobiliary diseases including, but not limited to: active hepatitis B virus or hepatitis C virus infection (see Exclusion Criterion 9), primary biliary cholangitis, complete biliary obstruction, acute cholecystitis or gallstones with significant symptoms, Autoimmune Hepatitis (AIH) or overlap with other autoimmune liver diseases, Alcoholic Hepatitis, Non-Alcoholic Steatohepatitis, Suspected or Diagnosed Primary Hepatocellular Cancer, and Bile Duct Cancer; 8. 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 9. Patients who are HBsAg-positive, HCVAb-positive, HIVAb-positive or TPAb-positive at screening 10. Cr(Creatinine)≥1.5×ULN also Cr(Creatinine)clearance rate\<60 mL/min 11. PLT(Platelet)\<80×10\^9/L 12. INR(international normalized ratio)\>1.3 13. ALB\<3.5g/dL 14. Severe pruritus may require systemic medication Within 2 months prior to randomization 15. Arrhythmia,male QTc≥450 ms,female QTc≥470 ms, during screening 16. 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 17. Moderate or intense inhibition of CYP3A4 was performed during 14 days prior to randomization and throughout the trial Preparation or inducer 18. 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 19. History of malignancy within the past 5 years prior to randomization 20. Immunosuppressants, budesonide, and other systemic glucocorticoids were used within 28 days before randomization and throughout the clinical study period; 21. Use of fenofibrate or another fibrate within 28 days prior to randomization and throughout the clinical study period; Hepatotoxic drugs; Hepatoprotective drugs and other hepatoprotective drugs were given stable doses \<28 days before randomization or could not maintain stable doses during the trial; cholagogue 22. Interleukin or other cytokines were used 12 months before randomization and throughout the trial Or antibodies to chemokines or immunotherapy 23. Drug and/or alcohol abuse within the first six months of randomization 24. Poor blood pressure control,systolic pressure\>160 mmHg or dpb \>100 mmHg 25. Poor blood sugar control,Glycated hemoglobin\>9.0% 26. Females who are pregnant or plan to pregnant,Fertile but refusing to sign informed consent, or breastfeed 27. Participated any other study within 30 days prior randomization,and received other experimental medications therapy 28. It is unsuitable to participate for the study or has other diseases by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AE incidence | Baseline to 12 weeks | AE incidence in placebo, 2mg and 4mg group |
| relative changes from baseline in ALP at week 12 | Baseline to 12 weeks | The reduction of percentage of ALP level from baseline to 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absulute changes from baseline in ALP at week 12 | Baseline to 12 weeks | The reduction of ALP level from baseline to 12 weeks |
| ALP and TBil changes | Baseline to 12 weeks | Compared with placebo, ALP\< 1.50 ULN, (total bilirubin) TBil ≤ULN |
| TBA changes | from basline to 12 weeks, and to 40 weeks | BA change from baseline |
| Pruritus incidence | from basline to 40 weeks | changes from baseline in the study period |
Countries
China
Contacts
STUDY_DIRECTORRong Deng
Cascade Pharmaceuticals, Inc
Outcome results
None listed