CS0159 in Chinese Patients With PBC (Primary Biliary Cholangitis)
- Conditions
- Primary Biliary Cholangitis (PBC)
- Interventions
- Drug: 2mg CS0159Drug: Placebo
- Registration Number
- NCT05896124
- Lead Sponsor
- Cascade Pharmaceuticals, Inc
- Brief Summary
A phase II study to evaluate safety, tolerability and efficacy of CS0159 in patients with PBC (Primary Biliary Cholangitis).
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 75
-
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≤ 3 × ULN
-
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
- 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.
- Patients were screened for HBsAg positive, HCVAb positive, HIV Ab positive, or TPAb positive.
- (creatinine, Cr) ≥1.5×ULN and Cr clearance rate <60 mL/min
- Platelet<80×10^9/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
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2mg CS0159 Placebo QD for 12 weeks 4mg CS0159 2mg CS0159 QD for 12 weeks Placebo Placebo QD for 12 weeks 2mg CS0159 2mg CS0159 QD for 12 weeks
- Primary Outcome Measures
Name Time Method relative changes from baseline in ALP at week 12 baseline to 12 weeks Compared with placebo ,Percentage change of CS0159 to ALP relative to baseline
AE incidence baseline to 12 weeks AE incidence in three arms
- Secondary Outcome Measures
Name Time Method Absulute changes from baseline in ALP at week 12 baseline to 12 weeks Compared with placebo, CS0159 changes in serum ALP relative to baseline
ALP and TBil baseline to 12 weeks Compared with placebo, the rate of subjects to achive the lelve of ALP\< 1.67 ULN and (total bilirubin) TBil ≤ULN
Pruritus from basline to 40 weeks the changes from baseline in Pruritus to week 40
Liver function: ALT, AST, ALB, LDL-C, HDL-C, TBA, GGT, TC, TG from baseline to week 40. The reduction of ALT, AST, ALB, LDL-C, HDL-C, TBA, GGT, TC, and TG from baseline to week 40.
Trial Locations
- Locations (16)
The First Affiliated Hospital of USTC Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Beijing Friendship Hospital, Captail Medcial University
🇨🇳Beijing, Beijing, China
Beijing Youan Hostital, Captial Medical University
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
The Third Affiliated Hospital, Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
The Fifth Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangzhou, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
Wuhan Union Hospital of China
🇨🇳Wuhan, Hubei, China
The Seconed Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The Third People's Hospital of Zhenjiang
🇨🇳Zhenjiang, Jiangsu, China
The First Bethune Hospital of Jilin University
🇨🇳ChangChun, Jilin, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Renji Hospital, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Shaoyifu Hospital of Zhejiang University Medical
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital,Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China