Clinical trial NCT05896124: CS0159 in Chinese Patients With PBC (Primary Biliary Cholangitis)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Primary Biliary Cholangitis (PBC)
Lead sponsor: Cascade Pharmaceuticals, Inc
Sponsor class: OTHER
First posted: 2023-06-09
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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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

Primary outcomes:
measure: AE incidence
timeFrame: baseline to 12 weeks
measure: relative changes from baseline in ALP at week 12
timeFrame: baseline to 12 weeks
Secondary outcomes:
measure: Absulute changes from baseline in ALP at week 12
timeFrame: baseline to 12 weeks
measure: ALP and TBil
timeFrame: baseline to 12 weeks
measure: Pruritus
timeFrame: from basline to 40 weeks
measure: Liver function: ALT, AST, ALB, LDL-C, HDL-C, TBA, GGT, TC, TG
timeFrame: from baseline to week 40.
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Friendship Hospital, Captail Medcial University
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hostital, Captial Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Fifth Affiliated Hospital of Guangzhou Medical University
state: Guangzhou
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital of China
state: Hubei
city: Changsha
country: China
facility: The Seconed Xiangya Hospital of Central South University
state: Hunan
city: Zhenjiang
country: China
facility: The Third People's Hospital of Zhenjiang
state: Jiangsu
city: ChangChun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Shaoyifu Hospital of Zhejiang University Medical
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital,Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Cascade Pharmaceuticals, Inc
name: Rong Deng
role: STUDY_DIRECTOR
References: