Non-alcoholic Fatty Liver Disease, Obesity, Type 2 Diabetes
Conditions
Brief summary
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
DRUGCS0159
The intervention will include a 12-week treatment period. During the 12-week treatment period, subjects will receive 4mg CS0159 (oral, once daily).
DRUGCS0159 placebo
The intervention will include a 12-week treatment period. During the 12-week treatment period, subjects will receive CS0159 placebo (oral, once daily).
DRUGSemaglutide
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).
Sponsors
Shanghai Jiao Tong University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in body weight relative to baseline | Baseline to 12 weeks | Evaluate the percentage change in body weight relative to baseline after 12 weeks of treatment. |
| Changes in energy expenditure | Baseline to 12 weeks | The impact of the patient's energy expenditure change relative to the baseline after 12 weeks, assessed by whole-room indirect calorimetry (metabolic chamber). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in patient's weight relative to the baseline | Baseline to 12 weeks | Evaluation of the change in patient's weight relative to the baseline after 12 weeks with CS0159 |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Baseline to 12 weeks | Evaluate the safety and tolerability of CS0159 combined with semaglutide during a 12-week treatment period |
| Change in patient's glucose oxidation | Baseline to 12 weeks | 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). |
| Change in patient's lipid oxidation | Baseline to 12 weeks | 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). |
| Percentage change in HbA1c relative to baseline | Baseline to 12 weeks | Evaluate the percentage change in glycated hemoglobin (HbA1c) relative to baseline after 12 weeks of treatment. |
| Changes relative to baseline in BMI | Baseline to 12 weeks | Changes in body mass index (BMI) relative to baseline after 12 weeks of administration |
| Changes relative to baseline in body composition | Baseline to 12 weeks | Changes in body composition analysis relative to baseline after 12 weeks of administration |
| Changes relative to baseline in waist circumference | Baseline to 12 weeks | Changes in waist circumference relative to baseline after 12 weeks of administration |
| Changes relative to baseline in waist to hip ratio (WHR) | Baseline to 12 weeks | Changes in waist to hip ratio (WHR) relative to baseline after 12 weeks of administration |
| Changes relative to baseline in serum liver function parameters | Baseline to 12 weeks | including alanine aminotransferase, aspartate aminotransferase, glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, direct bilirubin, total protein, albumin, and total bile acid. |
| Changes relative to baseline in serum lipid profile | Baseline to 12 weeks | including serum triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. |
| Changes relative to baseline in plasma glucose levels | Baseline to 12 weeks | including fasting plasma glucose and 2-hour post-prandial plasma glucose |
| Changes relative to baseline in serum insulin levels | Baseline to 12 weeks | including fasting serum insulin and 2-hour post-prandial serum insulin |
| Changes in peripheral blood metabolomics and proteomics relative to baseline | Baseline to 12 weeks | Changes in peripheral blood metabolomics and proteomics relative to baseline after 12 weeks of administration |
| Changes in fecal metabolites, gut microbiota homeostasis, and fecal gut microbiota metagenome relative to baseline | Baseline to 12 weeks | Changes in fecal metabolites, gut microbiota homeostasis, and fecal gut microbiota metagenome relative to baseline after 12 weeks of administration |
Contacts
CONTACTYifei Zhang
Outcome results
None listed