Efficacy, Safety, and Tolerability of CS0159 Combined With Semaglutide in MAFLD Patients With Obesity and T2DM

A Single -Center, Randomized, Double-blind, Placebo-controlled Proof of Exploratory Study Evaluating the Efficacy, Safety, and Tolerability of CS0159 Combined With Semaglutide in MAFLD Patients With Obesity and T2DM

This is an exploratory study evaluating CS0159 in combination with Semaglutide in metabolic dysfunction-associated fatty liver disease (MAFLD) patients with obesity and type 2 diabetes (T2DM).

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Type 2 Diabetes; Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: CS0159; Drug: Semaglutide; Drug: CS0159 placebo

Detailed Description

This is an exploratory study to evaluate the efficacy, safety, and tolerability of CS0159 in combination with Semaglutide in MAFLD patients with obesity and T2DM. Approximately 30 patients were randomly assigned to two groups in a 1:1 ratio for treatment for 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yifei Zhang; Phone Number: +86-13524640378; Email: feifei-a@163.com

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. MRI-PDFF ≥10% within 3 months prior to randomized.
• 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.
• 9. Can understand the research content, follow the research protocol, and voluntarily sign the ICF.

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: Triple

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 12 weeks	Drug: CS0159; The intervention will include a 12-week treatment period. During the 12-week treatment period, subjects will receive 4mg CS0159 (oral, once daily).; Drug: Semaglutide; The intervention will include a 12-week treatment period. During the 12-week treatment period, subjects will receive 0.5mg Semaglutide (subcutaneous injection, once weekly).
Placebo Comparator: CS0159 Placebo; CS0159 placebo (oral, once daily) + 0.5mg Semaglutide (subcutaneous injection, once weekly) for 12 weeks	Drug: Semaglutide; The intervention will include a 12-week treatment period. During the 12-week treatment period, subjects will receive 0.5mg Semaglutide (subcutaneous injection, once weekly).; Drug: CS0159 placebo; The intervention will include a 12-week treatment period. During the 12-week treatment period, subjects will receive CS0159 placebo (oral, once daily).

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 12 weeks of treatment.	Baseline to 12 weeks
Changes in energy expenditure	The impact of the patient's energy expenditure change relative to the baseline after 12 weeks, assessed by whole-room indirect calorimetry (metabolic chamber).	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patient's weight relative to the baseline	Evaluation of the change in patient's weight relative to the baseline after 12 weeks with CS0159	Baseline to 12 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Evaluate the safety and tolerability of CS0159 combined with semaglutide during a 12-week treatment period	Baseline to 12 weeks
Change in patient's glucose oxidation	Evaluation of the effect of CS0159 on glucose and lipid oxidation in patients relative to baseline after 12 weeks of administration, assessed by whole-room indirect calorimetry (metabolic chamber).	Baseline to 12 weeks
Change in patient's lipid oxidation	Evaluation of the effect of CS0159 on glucose and lipid oxidation in patients relative to baseline after 12 weeks of administration, assessed by whole-room indirect calorimetry (metabolic chamber).	Baseline to 12 weeks
Percentage change in HbA1c relative to baseline	Evaluate the percentage change in glycated hemoglobin (HbA1c) relative to baseline after 12 weeks of treatment.	Baseline to 12 weeks
Changes relative to baseline in BMI	Changes in body mass index (BMI) relative to baseline after 12 weeks of administration	Baseline to 12 weeks
Changes relative to baseline in body composition	Changes in body composition analysis relative to baseline after 12 weeks of administration	Baseline to 12 weeks
Changes relative to baseline in waist circumference	Changes in waist circumference relative to baseline after 12 weeks of administration	Baseline to 12 weeks
Changes relative to baseline in waist to hip ratio (WHR)	Changes in waist to hip ratio (WHR) relative to baseline after 12 weeks of administration	Baseline to 12 weeks
Changes relative to baseline in serum liver function parameters	including alanine aminotransferase, aspartate aminotransferase, glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, direct bilirubin, total protein, albumin, and total bile acid.	Baseline to 12 weeks
Changes relative to baseline in serum lipid profile	including serum triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol.	Baseline to 12 weeks
Changes relative to baseline in plasma glucose levels	including fasting plasma glucose and 2-hour post-prandial plasma glucose	Baseline to 12 weeks
Changes relative to baseline in serum insulin levels	including fasting serum insulin and 2-hour post-prandial serum insulin	Baseline to 12 weeks
Changes in peripheral blood metabolomics and proteomics relative to baseline	Changes in peripheral blood metabolomics and proteomics relative to baseline after 12 weeks of administration	Baseline to 12 weeks
Changes in fecal metabolites, gut microbiota homeostasis, and fecal gut microbiota metagenome relative to baseline	Changes in fecal metabolites, gut microbiota homeostasis, and fecal gut microbiota metagenome relative to baseline after 12 weeks of administration	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 15, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

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; Fatty Liver; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; semaglutide
• Other Study ID Numbers: MAFLD-CS0159-IIT-E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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