CS0159 in Chinese Patients With PBC (Primary Biliary Cholangitis)

Primary Biliary Cholangitis (PBC) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05896124
• Other study ID #: PBC-CS0159-004
• Status: Recruiting
• Phase: Phase 2
• Start date: August 7, 2023
• Est. completion date: October 2024

Study information

• Verified date: May 2023
• Source: Cascade Pharmaceuticals, Inc
• Contact: Rong Deng
• Phone: +86-021-68030121
• Email: dengrong[@]cascadepharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cholangitis (PBC)

Intervention

Drug:
• 2mg CS0159
Oral QD
• Placebo
Oral QD

Locations

Country	Name	City	State
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	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Bethune Hospital of Jilin University	ChangChun	Jilin
China	The Seconed Xiangya Hospital of Central South University	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The Fifth Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangzhou
China	The Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	Shaoyifu Hospital of Zhejiang University Medical	Hangzhou	Zhejiang
China	The First Affiliated Hospital,Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of USTC Anhui Provincial Hospital	Hefei	Anhui
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Renji Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Wuhan Union Hospital of China	Wuhan	Hubei
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	The Third People's Hospital of Zhenjiang	Zhenjiang	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Cascade Pharmaceuticals, Inc

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AE incidence	AE incidence in three arms	baseline to 12 weeks
Primary	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	Absulute changes from baseline in ALP at week 12	Compared with placebo, CS0159 changes in serum ALP relative to baseline	baseline to 12 weeks
Secondary	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
Secondary	Pruritus	the changes from baseline in Pruritus to week 40	from basline to 40 weeks
Secondary	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.