This is a phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MWN109 injection in non-diabetic participants with overweight or obesity.
Approximately 760 participants will be enrolled. All participants will be stratified by gender (male or female) and baseline BMI level, and then randomized 1:1:1:1 to 4 treatment groups, with 190 participants per group. All treatment groups will implement dose titration to achieve the target dose.
The study comprises a screening period of up to 2 weeks, a 52-week treatment period, and a 4-week follow-up period, for a total study duration of 58 weeks. The primary endpoints are the percentage change in body weight from baseline and the proportion of participants achieving ≥5% weight reduction from baseline at Week 52. The secondary endpoints include the proportions of participants achieving ≥10% and ≥15% weight reduction from baseline, as well as the change from baseline in waist circumference at Week 52.
Male or female aged 18 to 65 years (inclusive) at the time of signing the informed consent form;
Body weight ≥ 70 kg (males) or ≥ 60 kg (females), with BMI ≥ 28 kg/m² (obesity), or 24 kg/m² ≤ BMI < 28 kg/m² (overweight) with at least one weight-related comorbidity (e.g., hypertension, dyslipidemia, pre-diabetes, obstructive sleep apnea syndrome, metabolic dysfunction-associated steatotic liver disease, weight-bearing joint pain, cardiovascular disease, polycystic ovary syndrome);
Resting heart rate ≥ 55 bpm and ≤ 100 bpm (during screening and prior to randomization per 12-lead ECG);
Self-reported or documented history of dietary and exercise-based weight management for at least 12 weeks prior to screening, with < 5.0% weight change during the 12 weeks prior to screening, and ability to maintain the required diet and exercise behavior during the study;
Known allergic constitution (allergy to 3 or more foods or drugs), or allergy to GLP-1 receptor agonists or any component of the investigational product, or severe allergic diseases at screening, or history of severe drug allergy.
Use of any anti-hyperglycemic agents, weight-affecting medications, or prescription weight-loss medications for weight control within 12 weeks prior to screening; over-the-counter weight-loss medications or appetite suppressants within 4 weeks.
Laboratory abnormalities: ALT or AST ≥ 3×ULN; total bilirubin ≥ 1.5×ULN; eGFR < 60 mL/min/1.73m²; hemoglobin < 110 g/L (males) or < 100 g/L (females); serum calcitonin ≥ 35 ng/L; TSH > 6.0 or < 0.4 mIU/L; fasting triglycerides ≥ 5.64 mmol/L; serum amylase or lipase > 2.0×ULN.
Known or screening-detected ECG abnormalities with significant safety risk, including: uncontrolled arrhythmias, second-degree or third-degree AV block, ST-T changes suggesting myocardial ischemia, QTcF > 450 ms, family history of long QT or Brugada syndrome.