A Study of CS0159 in Patients With PBC With Inadequate Response or Intolerance to UDCA

A Randomized, Double-Blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of CS0159 in Patients With Primary Biliary Cholangitis (PBC) With Inadequate Response or Intolerance to Ursodeoxycholic Acid (UDCA)

A Randomized, Double-Blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of CS0159 in Patients with Primary Biliary Cholangitis (PBC) with inadequate response or intolerance to ursodeoxycholic acid (UDCA).

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Placebo; Drug: 2mg CS0159

Detailed Description

This is an multicenter, randomized, double-blind, placebo-controlled, parallel-group study that evaluates the efficacy and safety of CS0159 in patients with PBC who have inadequate response or intolerance to ursodeoxycholic acid (UDCA). Approximately 135 participants will be randomized in a 2:1 ratio to receive CS0159 (4 mg) or placebo, once daily, for a maximum of 52 weeks. When applicable, study participants should continue their pre-study dose of UDCA.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ma Xiong, MD; Phone Number: 15900984550; Email: maxiongmd@163.com
• Study Contact Backup: Name: Xiao Xiao, MD; Phone Number: 15921514136; Email: xxiao_sh@163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Anhui Medical University
      • Contact: Zhang Zhenhua
    • Hefei, Anhui, China, 230001
      • Not yet recruiting
      • The First Affiliated Hospital of USTC Anhui Provincial Hospital
      • Contact: He Hongliang
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100050
      • Not yet recruiting
      • Beijing Friendship Hospital, Capital Medical University
      • Contact: You Hong, MD
      • Contact: Jia Jidong
    • Beijing, Beijing Municipality, China, 100069
      • Not yet recruiting
      • Beijing Youan Hospital, Capital Medical University
      • Contact: Xu Bin
    • Beijing, Beijing Municipality, China
      • Not yet recruiting
      • China-Japan Friendship Hospital
      • Contact: Yang Song
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Not yet recruiting
      • Chongqing University Three Gorges Hospital
      • Contact: An Xuan
    • Chongqing, Chongqing Municipality, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Chongqing Medical University
      • Contact: Cai Dachuan
  • Fujian
    • Fuzhou, Fujian, China
      • Not yet recruiting
      • Mengchao Hepatobiliary Hospital OF Fujian Medical University
      • Contact: Huang Zuxiong
  • Guangdong
    • Shenzhen, Guangdong, China
      • Not yet recruiting
      • Peking University Shenzhen Hospital
      • Contact: Wu Jing
      • Contact: Hu Guoxin
    • Shenzhen, Guangdong, China
      • Not yet recruiting
      • Shenzhen Third People's Hospital
      • Contact: Chen Jun
    • Zhanjiang, Guangdong, China
      • Not yet recruiting
      • Affiliated Hospital of Guangdong Medical University
      • Contact: Han Huanqin
  • Guangxi
    • Nanning, Guangxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Guangxi Medical University
      • Contact: Su Minghua
  • Hebei
    • Shijiazhuang, Hebei, China
      • Not yet recruiting
      • Hebei medical university third hospital
      • Contact: Nan Yuemin
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Not yet recruiting
      • The Fourth Hospital of Harbin Medical University
      • Contact: Zhong Lihua
  • Henan
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Provincial People's Hospital
      • Contact: Shang Jia
  • Hubei
    • Shiyan, Hubei, China
      • Not yet recruiting
      • Taihe Hospital of Shiyan
      • Contact: Meng Zhongji
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Xiangya Hospital Central South University
      • Contact: Liu Xiaowei
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Jiangsu Province Hospital
      • Contact: Li Jun
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • The Second Hospital of Nanjing
      • Contact: Yang Yongfeng
    • Suzhou, Jiangsu, China
      • Not yet recruiting
      • The Fifth People's Hospital of Suzhou
      • Contact: Zhu Chuanwu
    • Wuxi, Jiangsu, China
      • Not yet recruiting
      • The Fifth People's Hospital of Wuxi
      • Contact: Wang Zheng
    • Zhenjiang, Jiangsu, China
      • Not yet recruiting
      • The Third People's Hospital of Zhenjiang
      • Contact: Tan Youwen; Phone Number: 0511-80578875
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Wu Xiaoping
    • Nanchang, Jiangxi, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Nanchang University
      • Contact: Wen Zhili
  • Jilin
    • Changchun, Jilin, China
      • Not yet recruiting
      • The First Bethune Hospital of Jilin University
      • Contact: Niu Junqi
  • Liaoning
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • The Sixth People's Hospital of Shenyang
      • Contact: Wu Xiaofeng
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • The First Hospital of China Medical University
      • Contact: Li Yiling
  • Shaanxi
    • Baoji, Shaanxi, China
      • Not yet recruiting
      • Baoji People's Hospital
      • Contact: Jing Fuchun
    • Xi'an, Shaanxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: He Yinli
  • Shandong
    • Linyi, Shandong, China
      • Not yet recruiting
      • Linyi people's hospital
      • Contact: Gao Feng
    • Qingdao, Shandong, China
      • Not yet recruiting
      • The Affiliated Hospital Of Qingdao University
      • Contact: Jiang Yueping
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200001
      • Recruiting
      • Renji Hospital, School of Medicine, Shanghai Jiao Tong University
      • Contact: Ma Xiong, MD; Phone Number: 15900984550; Email: maxiongmd@163.com
    • Shanghai, Shanghai Municipality, China
      • Not yet recruiting
      • Shanghai Jiao Tong University School of Medicine Ruijin Hospital
      • Contact: Xie Qing
    • Shanghai, Shanghai Municipality, China
      • Not yet recruiting
      • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Fan Jiangao
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • West China Hospital, Sichuan University
      • Contact: Yang Li
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Not yet recruiting
      • Tianjin Medical University General Hospital
      • Contact: Wang Bangmao
    • Tianjin, Tianjin Municipality, China
      • Not yet recruiting
      • Tianjin First Central Hospital
      • Contact: Wang Fengmei
    • Tianjin, Tianjin Municipality, China
      • Not yet recruiting
      • Tianjin Third Central Hospital
      • Contact: Xiang Huiling
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Hangzhou Xixi Hospital
      • Contact: Jin Qiaofei
    • Taizhou, Zhejiang, China
      • Not yet recruiting
      • Taizhou Hospital of Zhejiang Province
      • Contact: Chen Huazhong
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Zheng Minghua

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Must have given written informed consent (signed and dated) and any authorizations required by local law;
2. When signing ICF age ≥18 years ≤75 years, male or female;

3. Meets the diagnostic criteria of PBC, based on any two of the following criteria:

   1. History of ALP above 1.0× ULN for at least 6 months
   2. Positive antimitochondrial antibody (AMA) titer (>1:40 on immunofluorescence or M2 positive by ELISA) or positive PBC- specific antinuclear antibody (ANA) (either SP100 or GP210 positive)
   3. Documented liver biopsy results consistent with PBC;
4. UDCA≥6 months before randomization and a stable dose ≥3 months after the efficacy was poor [meeting inclusion criteria (5)a], or UDCA was not tolerated, and stop taking UDCA (no UDCA use for ≥3 months before randomization);

5. Central laboratory parameters measured at screening period meet the following criteria:

   1. ALP ≥1.67× ULN
   2. ALT≤5× ULN
   3. AST ≤5× ULN
   4. TB <2× ULN
   5. Estimated glomerular filtration rate (eGFR) > 60mL/min/1.73m2 (calculated by CKD-EPI equation)
   6. INR ≤ 1.0× ULN. For participants on anticoagulation therapy, INR must be maintained in the range required for prophylaxis for their specific disease
   7. Platelet count ≥ 150× 109/μL (No thrombocytopenia-related treatment within the past two weeks)
   8. Albumin> 35g/L
   9. White blood cells count (WBC) >3×109/L
   10. Absolute neutrophil count (ANC) >1.5×109/L
   11. Hemoglobin A1c (HbA1c) ≤9.0%;

6. Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male participants who are sexually active with female partners of reproductive potential must use barrier contraception, and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose.

   -

Exclusion Criteria:

1. Previous exposure to CS0159;
2. History of allergy to the CS0159 or its excipients or drugs of similar chemical classes;
3. Advanced PBC as defined by the Rotterdam criteria (albumin<1.0×LLN AND TB >1.0× ULN);

4. Patients who have had clinically significant complications of hepatic cirrhosis with clinically significant portal hypertension (CSPH), including the following:

   1. History of liver transplantation, current placement on a liver transplant list, current MELD -Na score ≥ 12;
   2. History of confirmed esophagogastric variceal bleeding;
   3. Clinically significant ascites requiring intervention, such as sodium restriction, diuretic therapy, or therapeutic paracentesis;
   4. Any secondary complications resulting from clinically significant ascites, such as spontaneous bacterial peritonitis, hepatorenal syndrome, or hepatic hydrothorax;
   5. Hepatic encephalopathy requiring drug therapy;
   6. Portopulmonary hypertension and/or hepatopulmonary syndrome;
   7. Hepatocellular carcinoma;

5. Other concomitant liver disease including:

   1. Autoimmune hepatitis (AIH) (simplified AIH diagnostic score >6), PBC-AIH overlap syndrome, or overlap with other autoimmune liver diseases
   2. Positive HBsAg or positive HCV RNA (tested for in case of known cured HCV infection or positive HCV Ab at screening)
   3. Primary sclerosing cholangitis (PSC)
   4. History or clinical evidence of Alcoholic liver disease (ALD)
   5. Biopsy confirmed Non-alcoholic steatohepatitis (NASH)
   6. Gilbert's Syndrome
   7. History or evidence of alpha-1 antitrypsin deficiency
   8. Liver stiffness measured by transient elastography (TE) > 16.9 Kpa;
6. Patient has a positive test for HIV at screening, or active syphilis [defined as positive Treponema pallidum antibody (TP Ab) and a rapid plasma reagin (RPR) card test titer ≥1:8; for low titers (e.g., 1:1 or 1:2), clinical judgment is required to determine if it is active syphilis];

7. Administration of the following medications are prohibited as specified below:

   1. Use of medications, food, and drinks (e.g., grapefruit juice) that are strong or moderate CYP3A4 inhibitors or inducers within 14 days before randomization;
   2. Use of P-glycoprotein (P-gp) substrate drugs within 14 days before randomization;
   3. 2 months prior to randomization: fibrates, glitazones, seladelpar and elafibranor.
   4. 3 months prior to randomization: obeticholic acid (OCA), azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, systemic corticosteroids and budesonide (˃2 weeks); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin).
   5. Patients with systemic treatment for pruritus (e.g., with bile acid sequestrants [BAS]) within 3 months prior to randomization.
   6. 12 months prior to randomization: antibodies or immunotherapy directed against ILs or other cytokines or chemokines;
8. Medical conditions that may cause non-hepatic increases in ALP (e.g., paget's disease);
9. Patients with severe arrhythmia, or a QTcF interval corrected by Fridericia's formula ≥450 ms (males) or ≥470 ms (females) at screening [Fridericia's formula: QTcF=QT/(RR^0.33)];
10. 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);
11. History of malignancy (except for those with a disease-free survival of ≥5 years) or currently under evaluation for malignancy; except for cured squamous or non-invasive skin basal cell carcinoma and cervical carcinoma in situ;
12. Drug abuse or heavy alcohol use from 12 months prior to randomization throughout the entire clinical study period. Heavy alcohol use is defined as an average weekly alcohol consumption of more than approximately 7 standard drinks for females and more than approximately 14 standard drinks for males. One standard drink is defined as any beverage containing 14g of pure alcohol, such as 12 oz/360 mL of beer (5% alcohol), 8 oz/240 mL of malt liquor (7% alcohol), 5 oz/150 mL of wine (12% alcohol), or 1.5 oz/45 mL of distilled spirits (40% alcohol);
13. Poor blood pressure control is indicated after treatment by a systolic pressure greater than 160 mmHg or diastolic pressure greater than 100 mmHg during screening;
14. Pregnancy, planned pregnancy, lactation;
15. Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening;
16. Mental instability or incompetence that may compromise the validity of informed consent or ability to adhere to study requirements;

17. 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4 mg CS0159; Take 4mg of CS0159 QD for 52 weeks.	Drug: 2mg CS0159; Oral QD
Placebo Comparator: placebo; Take placebo QD for 52 weeks.	Drug: Placebo; Oral QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients who achieve the composite response criteria at Week 52	ALP < 1.67×ULN; and ALP decrease of ≥15%; and TB ≤1.0× ULN	Baseline to week 52 .

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to treatment based on γ-glutamyl transpeptidase (GGT) normalization in patients with baseline GGT>1.0× ULN at Week 26 and Week 52		Basline to week 26 and week 52 .
Response to treatment based on alanine aminotransferase (ALT) normalization in patients with baseline ALT >1.0× ULN at Week 26 and Week 52		Basline to week 26 and week 52 .
Proportion of patients with ALP< 1.67× ULN and TB ≤1.0× ULN and ALP decrease of ≥15% from baseline at Week 26		Baseline to week 26 .
Response to treatment based on AST normalization in patients with baseline AST>1.0× ULN at Week 26 and Week 52		Baseline to week 26 and week 52 .
Proportion of patients with ALP≤ 3× ULN and AST ≤ 2 × ULN and TB≤ 1.0×ULN at Week 52		Baseline to week 52 .
The first occurrence of clinical outcome events as defined	Overall death Liver transplantation Model for End-Stage Liver Disease (MELD)-Na score >14 for at least 2 consecutive visits Ascites requiring treatment Hospitalization for new onset or recurrence of any of the following: i. Variceal bleeding ii. Hepatic encephalopathy (as defined by a West Haven score ≥2) iii. Spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis).	up to 56 weeks
Assessment of treatment-emergent AEs (TEAEs)	Safety	up to 56 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Absolute changes of liver stiffness measured by iLivTouch	week 26, week 52

Collaborators and Investigators

• Sponsor: Cascade Pharmaceuticals, Inc
• Investigators: Principal Investigator: Ma Xiong, MD, Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 9, 2027
• Study Completion (Estimated): January 6, 2028

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Estimated): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

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: CS0159-PBC-CN-III-07

Drug and device information, study documents

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