CS0159 in Chinese Patients With PBC (Primary Biliary Cholangitis)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Biliary Cholangitis (PBC)
• Intervention / Treatment: Drug: Placebo; Drug: 2mg CS0159

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • The First Affiliated Hospital of USTC Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing Municipality, China, 100069
      • Beijing Youan Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China, 100050
      • Beijing Friendship Hospital, Capitai Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital, Sun Yat-sen University
  • Guangzhou
    • Guangzhou, Guangzhou, China
      • The Fifth Affiliated Hospital of Guangzhou Medical University
  • Henan
    • Zhengzhou, Henan, China
      • Henan Provincial People's Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital of China
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Seconed Xiangya Hospital of Central South University
  • Jiangsu
    • Zhenjiang, Jiangsu, China
      • The Third People's Hospital of Zhenjiang
  • Jilin
    • Changchun, Jilin, China
      • The First Bethune Hospital Of Jilin University
  • Shandong
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200120
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital，Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310000
      • Shaoyifu Hospital of Zhejiang University Medical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. When signing ICF age≥18 years≤75 years, male or female
2. 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
3. 1.67 × ULN ≤ALP ≤ 10 × ULN and TBil≤ 3 × ULN
4. 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)

5. Understand the study content, comply with the study protocol, and sign the ICF voluntarily

   -

Exclusion Criteria:

1. ALT or AST>5×ULN；
2. OCA(Obercholic acid) in the 3 months prior to randomization
3. Known concomitant hepatobiliary disease or history
4. 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.
5. Patients were screened for HBsAg positive, HCVAb positive, HIV Ab positive, or TPAb positive.
6. (creatinine, Cr) ≥1.5×ULN and Cr clearance rate <60 mL/min
7. Platelet<80×10^9/L；
8. INR>1.3
9. ALB<3.5 g/dL
10. Severe pruritus or systemic medication was required within 2 months prior to randomization
11. Arrhythmia, Or during screening the QTc interval was ≥450 ms for male and 470 ms for female
12. 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).
13. 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.
14. 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
15. A history of malignant tumor within 5 years prior to randomization
16. Perazathioprine, colchicine, cyclosporine, methotrexate, mycophenolate, and pentoxifylline were administered from 28 days before randomization to the entire clinical study period. Fenofibrate or other Bates; Budesonide and other systemic corticosteroid hormones; Hepatotoxic drugs; Liver protection Drugs and other hepatoprotective drugs were given a stable dose <28 days before randomization or could not be maintained during the trial; cholagogue
17. 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
18. Substance abuse or alcoholism from 6 months prior to randomization throughout the entire clinical study period
19. Poor blood pressure control is indicated by a systolic pressure greater than 160 mmHg or diastolic pressure greater than 100 mmHg during screening
20. Poor blood glucose control, that is, HBA1c >9.0% at screening
21. Pregnancy, planned pregnancy, lactation
22. Use of other investigational drugs within 3 months
23. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2mg CS0159; QD for 12 weeks	Drug: Placebo; Oral QD; Drug: 2mg CS0159; Oral QD
Experimental: 4mg CS0159; QD for 12 weeks	Drug: 2mg CS0159; Oral QD
Experimental: Placebo; QD for 12 weeks	Drug: Placebo; Oral QD

What is the study measuring?

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-C, HDL-C, TBA, GGT, TC, TG	The reduction of ALT, AST, ALB, LDL-C, HDL-C, TBA, GGT, TC, and TG from baseline to week 40.	from baseline to week 40.

Collaborators and Investigators

• Sponsor: Cascade Pharmaceuticals, Inc
• Investigators: Study Director: Rong Deng, Cascade Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): March 15, 2026

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: June 7, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis, Biliary
• Other Study ID Numbers: PBC-CS0159-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No