CS0159 in Chinese Patients With PSC (Primary Sclerosing Cholangitis)

Primary Sclerosing Cholangitis Clinical Trial

Official title:

A Phase II Study to Evaluate Safety, Tolerability and Efficacy, of CS0159 in Patients Subjects With Primary Sclerosing Cholangitis, Multicenter, Randomized, 12-week Double-blind, Placebo-controlled, and 40-week Open Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05896137
• Other study ID #: PSC-CS0159-003
• Status: Recruiting
• Phase: Phase 2
• Start date: August 7, 2023
• Est. completion date: December 2024

Study information

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

Clinical Trial Summary

A phase II Study of CS0159 in Chinese patients with PSC(Primary Sclerosing Cholangitis)

Description:

A phase II study to evaluate safety, tolerability and efficacy, of CS0159 in patients with Primary Sclerosing Cholangitis, this is a multicenter, randomized, 12-weeks double-blind, placebo-controlled, and 40-week open study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female age=18 or age=75 years when sign ICF

2. Within the last year, have a clinical diagnosis of PSC with a consistent magnetic resonance cholangiopancreatography (MRCP) orendoscopic retrograde cholangiopancreatography (ERCP) Prcutaneous Transhepatic Cholangiography(PTC) showing sclerosing cholangitis

3. 1.50×ULN=ALP=10×ULN, and TBil=3×ULN during screen

4. Taken UDCA(=25mg/kg/d)=6 months before randomization and stable does= 3 months, or not used UDCA=3 months before randomization

5. For subject with a history of IBD

1. Patients with Crohn's Disease (CD),Must be in remission, CDAI<150 or CDAI of score =4

2. Patients with(Ulcerative Colitis)UC,Must be in remission or only mild activity,Some Mayo scores range from 0 to 4

6. Be able to understand and Comply with the study protocol sign a written informed consent form(ICF)voluntarily

Exclusion Criteria,

1. Presence of documented secondary sclerosing cholangitis when screening,or direct evidence IgG4 related sclerosing cholangitis or serum IgG4 = 4 ×ULN

2. Small duct PSC

3. ALT or AST>5×ULN

4. Taken( ObeticholicAcid) OCA within 3 months before randomization

5. Acute cholangitis was suspected or confirmed within 3 months prior to randomization, Including acute cholangitis being treated during screening

6. Presence of percutaneous drain or bile duct stent at the time of screening or during the study

7. Known concurrent comorbidities with other hepatobiliary diseases including, but not limited to: active hepatitis B virus or hepatitis C virus infection (see Exclusion Criterion 9), primary biliary cholangitis, complete biliary obstruction, acute cholecystitis or gallstones with significant symptoms, Autoimmune Hepatitis (AIH) or overlap with other autoimmune liver diseases, Alcoholic Hepatitis, Non-Alcoholic Steatohepatitis, Suspected or Diagnosed Primary Hepatocellular Cancer, and Bile Duct Cancer;

8. Child-Pugh patients with grade B or C cirrhosis,Present complications related to cirrhosis or End-stage liver disease ,Including history of liver transplantation Preparing for liver transplantation (Model for End-Stage Liver Disease)MELD=15,Portal hypertension complications,Complications of cirrhosis

9. Patients who are HBsAg-positive, HCVAb-positive, HIVAb-positive or TPAb-positive at screening

10. Cr(Creatinine)=1.5×ULN also Cr(Creatinine)clearance rate<60 mL/min

11. PLT(Platelet)<80×10^9/L

12. INR(international normalized ratio)>1.3

13. ALB<3.5g/dL

14. Severe pruritus may require systemic medication Within 2 months prior to randomization

15. Arrhythmia,male QTc=450 ms,female QTc=470 ms, during screening

16. A disease that interferes with the absorption, distribution, metabolism, or excretion of a test drug,such as moderate to severe activity IBD patient, Previous gastric bypass surgery

17. Moderate or intense inhibition of CYP3A4 was performed during 14 days prior to randomization and throughout the trial Preparation or inducer

18. The presence of diseases that may cause non-hepatic elevation of ALP (e.g. Paget's disease) or may cause it Diseases with a life expectancy of less than 2 years

19. History of malignancy within the past 5 years prior to randomization

20. Immunosuppressants, budesonide, and other systemic glucocorticoids were used within 28 days before randomization and throughout the clinical study period;

21. Use of fenofibrate or another fibrate within 28 days prior to randomization and throughout the clinical study period; Hepatotoxic drugs; Hepatoprotective drugs and other hepatoprotective drugs were given stable doses <28 days before randomization or could not maintain stable doses during the trial; cholagogue

22. Interleukin or other cytokines were used 12 months before randomization and throughout the trial Or antibodies to chemokines or immunotherapy

23. Drug and/or alcohol abuse within the first six months of randomization

24. Poor blood pressure control,systolic pressure>160 mmHg or dpb >100 mmHg

25. Poor blood sugar control,Glycated hemoglobin>9.0%

26. Females who are pregnant or plan to pregnant,Fertile but refusing to sign informed consent, or breastfeed

27. Participated any other study within 30 days prior randomization,and received other experimental medications therapy

28. It is unsuitable to participate for the study or has other diseases by the investigator

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• CS0159 2mg
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	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

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 placebo, 2mg and 4mg group	Baseline to 12 weeks
Primary	relative changes from baseline in ALP at week 12	The reduction of percentage of ALP level from baseline to 12 weeks	Baseline to 12 weeks
Secondary	Absulute changes from baseline in ALP at week 12	The reduction of ALP level from baseline to 12 weeks	Baseline to 12 weeks
Secondary	ALP and TBil changes	Compared with placebo, ALP< 1.50 ULN, (total bilirubin) TBil =ULN	Baseline to 12 weeks
Secondary	TBA changes	BA change from baseline	from basline to 12 weeks, and to 40 weeks
Secondary	Pruritus incidence	changes from baseline in the study period	from basline to 40 weeks