Efficacy and Safety of CS0159 Combined With Semaglutide in MASH Patients With Obesity and T2DM

A Multi-center, Randomized, Double-blind, Placebo-controlled Proof of Concept Study Evaluating the Efficacy, Safety, and Tolerability of CS0159 Combined With Semaglutide in MASH Patients With Obesity and T2DM

This is an exploratory study evaluating CS0159 in combination with Semaglutide in MASH patients with obesity and T2DM.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus, Type 2; Metabolic Dysfunction-Associated Steatohepatitis (MASH)
• Intervention / Treatment: Drug: CS0159; Drug: CS0159 placebo

Detailed Description

This is an exploratory study to evaluate the efficacy, safety, and tolerability of CS0159 in combination with Semaglutide in MASH patients with obesity and T2DM. A total of 60 patients will be recruited. BMI ≥35 kg/m2 will be used as a randomized stratification factor, and patients will be randomly assigned in a 1:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Dep.endocrinology of Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age≥18 and ≤65 years, male or female.
• 2. Patients with previous liver biopsy for MASH or MRI-PDFF ≥10% within 3 months prior to randomization.
• 3. Diagnosis of T2DM.
• 4. HbA1c: 7.0%-10.5%.
• 5. FPG: 7.0-13.3 mmol/L.
• 6. BMI: 30-45 kg/m2.
• 7. Subjects control blood glucose only by lifestyle intervention for at least 3 months before the screening period.
• 8. Willing to maintain consistent diet and exercise habits throughout the entire study, and adhere to the study protocol for timely administration of the study drug, and timely self-monitoring of blood glucose and recording.

Exclusion Criteria:

• 1. ALT≥2.5×ULN, AST≥2.5×ULN, TBil≥2×ULN, creatinine (Cr) ≥1.5×ULN and Serum creatinine clearance<60 mL/min, PLT<100×10^9/L, INR >1.3, ALB <3.5 g/dL.
• 2. Use of glucose-lowering medication in the 3 months prior to randomization.
• 3. Weight loss ≥ 5% in the 3 months prior to randomization or ≥10% in the 6 months prior to randomization or use of other weight-lowering drugs, corticosteroids, and etc.
• 4. History of allergy to glucagon-like peptide-1 receptor agonists (GLP-1RA) medications, currently in an allergic state, having allergic conditions, or history of allergies to ≥2 substances.
• 5. Subjects with T1DM, monogenic diabetes, diabetes caused by pancreatic damage, or other secondary diabetes.
• 6. Subjects with a history of severe pruritus.
• 7. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy.
• 8. Thyroid C-cell tumour or family history, multiple endocrine neoplasia type 2 or family history.
• 9. History of acute or chronic pancreatitis.
• 10. Subjects with Child-Pugh class B or C grade cirrhosis.
• 11. HBsAg positive, HCV Ab positive, HIV Ab positive, TP Ab positive.
• 12. Arrhythmias, male QTc≥450 ms, or female QTc≥470 ms. Or cardiovascular disease for which the researcher has assessed that participation in the trial is not appropriate.
• 13. Diseases that interfere with the absorption, distribution, metabolism or excretion.
• 14. Gastrointestinal diseases that affect food digestion and absorption.
• 15. Use moderate or strong inhibitors or inducers of cytochrome P450 enzyme (CYP3A4 enzyme) within the first 14 days of randomization and throughout the entire trial period.
• 16. History of malignant tumors within the first 5 years of randomization.
• 17. Serious hypoglycemic events occurring ≥ 3 times within 12 weeks prior to administration, or acute and severe metabolic disorder occurred within 12 weeks prior to administration.
• 18. Drug abuse or alcohol abuse within the first 6 months of randomization.
• 19. Poor blood pressure control.
• 20. Mental illness, epilepsy.
• 21. Patients with uncontrollable severe infectious diseases before randomization.
• 22. Pregnant, planned pregnancy or breastfeeding.
• 23. Participated in other clinical trials in the first three months of randomization.
• 24. Any condition that in the judgement of the researcher precludes participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 4mg CS0159; 4mg CS0159 (oral, once daily) + 0.5mg Semaglutide (subcutaneous injection, once weekly) for 16 weeks	Drug: CS0159; The intervention will include a 2-week screening period, a 16-week treatment period, and a 4-week follow-up period. Efficacy and safety evaluations will be conducted after the end of the treatment. During the 16-week treatment period, subjects will receive 4mg CS0159 (oral, once daily) + 0.5mg Semaglutide (subcutaneous injection, once weekly).
Placebo Comparator: CS0159 Placebo; CS0159 placebo (oral, once daily) + 0.5mg Semaglutide (subcutaneous injection, once weekly) for 16 weeks	Drug: CS0159 placebo; The intervention will include a 2-week screening period, a 16-week treatment period, and a 4-week follow-up period. Efficacy and safety evaluations will be conducted after the end of the treatment. During the 16-week treatment period, subjects will receive CS0159 placebo (oral, once daily) + 0.5mg Semaglutide (subcutaneous injection, once weekly).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in body weight relative to baseline	Evaluate the percentage change in body weight relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Safety outcomes	Baseline to 16 weeks
Patient Health Questionnaire 9 (PHQ-9)	Safety outcomes	Baseline to 16 weeks
Short form 36 health survey questionnaire (SF-36)	Safety outcomes	Baseline to 16 weeks
Visual analog scale for pruritus and 5-D itch scale	Safety outcomes	Baseline to 16 weeks
Proportion of subjects achieving ≥5% weight loss	Proportion of subjects achieving ≥5% weight loss from baseline after 16 weeks of treatment.	Baseline to 16 weeks
Percentage change in HbA1c relative to baseline	Evaluate the percentage change in glycated hemoglobin (HbA1c) relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
Fasting plasma glucose levels	Changes in fasting plasma glucose levels relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
2-hour post-prandial plasma glucose levels	Changes in 2-hour post-prandial plasma glucose levels relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
Fasting serum insulin levels	Changes in fasting serum insulin levels relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
2-hour post-prandial serum insulin levels	Changes in 2-hour post-prandial serum insulin levels relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
Fasting serum C peptide levels	Changes in fasting serum C peptide levels relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
2-hour post-prandial serum C peptide levels	Changes in 2-hour post-prandial serum C peptide levels relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
Percentage change in liver fat content relative to baseline	Evaluate the percentage change in liver fat content measured by Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
Changes relative to baseline in body mass index (BMI)	Changes in BMI (=body weight/height^2) relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
Changes relative to baseline in body composition	Changes in body composition relative to baseline after 16 weeks of treatment, including lean mass, fat mass, body fat percentage and etc.	Baseline to 16 weeks
Changes relative to baseline in waist circumference and waist-to-hip ratio (WHR)	Changes in waist circumference and waist-to-hip ratio (=waist circumference/hip circumference) relative to baseline after 16 weeks of treatment.	Baseline to 16 weeks
Changes relative to baseline in liver function	including alanine aminotransferase, aspartate aminotransferase，ɣ-glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, direct bilirubin, total protein, albumin, and total bile acid.	Baseline to 16 weeks
Changes relative to baseline in renal function	including including serum urea nitrogen, serum creatinine, and serum urinary acid.	Baseline to 16 weeks
Changes relative to baseline in lipid profile	including serum triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol.	Baseline to 16 weeks
Changes relative to baseline in parameters of hepatic fibrosis	including serum hyaluronic acid, laminin, procollagen type III, and collagen type IV.	Baseline to 16 weeks

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): April 22, 2025

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 31, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Digestive System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Liver Diseases; Overweight; Obesity; Diabetes Mellitus, Type 2; Fatty Liver
• Other Study ID Numbers: MASH-CS0159-IIT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No