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

Official title

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

Overview

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).

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.

Interventions

• 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 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).
• 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).

Primary outcome measures

• Percentage change in body weight relative to baseline [Time frame: Baseline to 12 weeks]
• Changes in energy expenditure [Time frame: Baseline to 12 weeks]

Secondary outcome measures (12)

• Change in patient's weight relative to the baseline [Time frame: Baseline to 12 weeks]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Time frame: Baseline to 12 weeks]
• Change in patient's glucose oxidation [Time frame: Baseline to 12 weeks]
• Change in patient's lipid oxidation [Time frame: Baseline to 12 weeks]
• Percentage change in HbA1c relative to baseline [Time frame: Baseline to 12 weeks]
• Changes relative to baseline in BMI [Time frame: Baseline to 12 weeks]
• Changes relative to baseline in body composition [Time frame: Baseline to 12 weeks]
• Changes relative to baseline in waist circumference [Time frame: Baseline to 12 weeks]
• Changes relative to baseline in waist to hip ratio (WHR) [Time frame: Baseline to 12 weeks]
• Changes relative to baseline in serum liver function parameters [Time frame: Baseline to 12 weeks]
• Changes relative to baseline in serum lipid profile [Time frame: Baseline to 12 weeks]
• Changes relative to baseline in plasma glucose levels [Time frame: Baseline to 12 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07570810 · MAFLD-CS0159-IIT-E

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗