Clinical trial NCT06492330: Efficacy and Safety of CS0159 Combined With Semaglutide in MASH Patients With Obesity and T2DM
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Obesity
Diabetes Mellitus, Type 2
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2024-07-09
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage change in body weight relative to baseline
timeFrame: Baseline to 16 weeks
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Baseline to 16 weeks
measure: Patient Health Questionnaire 9 (PHQ-9)
timeFrame: Baseline to 16 weeks
measure: Short form 36 health survey questionnaire (SF-36)
timeFrame: Baseline to 16 weeks
measure: Visual analog scale for pruritus and 5-D itch scale
timeFrame: Baseline to 16 weeks
measure: Proportion of subjects achieving ≥5% weight loss
timeFrame: Baseline to 16 weeks
measure: Percentage change in HbA1c relative to baseline
timeFrame: Baseline to 16 weeks
measure: Fasting plasma glucose levels
timeFrame: Baseline to 16 weeks
measure: 2-hour post-prandial plasma glucose levels
timeFrame: Baseline to 16 weeks
measure: Fasting serum insulin levels
timeFrame: Baseline to 16 weeks
measure: 2-hour post-prandial serum insulin levels
timeFrame: Baseline to 16 weeks
measure: Fasting serum C peptide levels
timeFrame: Baseline to 16 weeks
measure: 2-hour post-prandial serum C peptide levels
timeFrame: Baseline to 16 weeks
measure: Percentage change in liver fat content relative to baseline
timeFrame: Baseline to 16 weeks
measure: Changes relative to baseline in body mass index (BMI)
timeFrame: Baseline to 16 weeks
measure: Changes relative to baseline in body composition
timeFrame: Baseline to 16 weeks
measure: Changes relative to baseline in waist circumference and waist-to-hip ratio (WHR)
timeFrame: Baseline to 16 weeks
measure: Changes relative to baseline in liver function
timeFrame: Baseline to 16 weeks
measure: Changes relative to baseline in renal function
timeFrame: Baseline to 16 weeks
measure: Changes relative to baseline in lipid profile
timeFrame: Baseline to 16 weeks
measure: Changes relative to baseline in parameters of hepatic fibrosis
timeFrame: Baseline to 16 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Dep.endocrinology of Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References: