Clinical trial NCT05896137: CS0159 in Chinese Patients With PSC (Primary Sclerosing Cholangitis)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Lead sponsor: Cascade Pharmaceuticals, Inc
Sponsor class: OTHER
First posted: 2023-06-09
Enrollment: 50
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 of CS0159 in Chinese patients with PSC(Primary Sclerosing Cholangitis)

Detailed 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.

Eligibility criteria: 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

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 changes
timeFrame: Baseline to 12 weeks
measure: TBA changes
timeFrame: from basline to 12 weeks, and to 40 weeks
measure: Pruritus incidence
timeFrame: from basline to 40 weeks
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: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
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: 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: 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: