Phase 2 Clinical Study of MWN105 Injection in Participants With Overweight or Obesity

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study to Evaluate the Pharmacokinetic Characteristics, Efficacy, and Safety of MWN105 Injection in Non-Diabetic Participants With Overweight or Obesity

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the pharmacokinetic characteristics, efficacy, and safety of MWN105 Injection in non-diabetic participants with overweight or obesity.

Approximately 120 participants will be randomized to receive different dose levels of MWN105 Injection or matching placebo, administered subcutaneously once weekly for a total treatment duration of 24 weeks, with dose titration from 15 mg to the target dose.

The primary endpoint is the percent change from baseline in body weight at Week 24. Secondary endpoints include changes in body weight and metabolic parameters, bone mineral density, pharmacokinetic parameters, immunogenicity, and safety.

Inclusion Criteria:

1. Male or female participants aged 18 to 65 years (inclusive) at the time of signing the informed consent form (ICF).
2. Body weight ≥ 70 kg (male) or ≥ 60 kg (female), with body mass index (BMI) ≥ 30 kg/m² (obesity), or 27 kg/m² ≤ BMI < 30 kg/m² (overweight) accompanied by at least one weight-related comorbidity (e.g., hypertension, dyslipidemia, prediabetes, obstructive sleep apnea syndrome, metabolic dysfunction-associated steatotic liver disease, weight-bearing joint pain, cardiovascular disease, or polycystic ovary syndrome).
3. Self-reported or documented diet and exercise control of body weight for 12 weeks or more, with body weight change of less than 5.0% within 12 weeks prior to screening.

Exclusion Criteria:

1. Known hypersensitivity to GLP-1 receptor agonists, any component of the investigational product, or history of severe allergic disease or severe drug allergy.

2. Use of medications that may affect glucose metabolism or body weight before screening, including antidiabetic drugs, systemic glucocorticoids, psychotropic drugs associated with weight change, prescription weight-loss drugs within 12 weeks, or over-the-counter weight-loss drugs/appetite suppressants within 4 weeks.

3. Clinically significant laboratory abnormalities at screening or before randomization, including:

   1. ALT or AST ≥3 × ULN, or TBIL ≥1.5 × ULN.
   2. eGFR <60 mL/min/1.73 m².
   3. Hemoglobin <110 g/L in males or <100 g/L in females.
   4. Calcitonin ≥35 ng/L.
   5. TSH >6.0 or <0.4 mIU/L.
   6. Fasting triglycerides ≥5.64 mmol/L.
   7. Amylase or lipase >2 × ULN.

4. History or presence of clinically significant diseases or conditions that may affect body weight, safety, or study assessments, including:

   1. Secondary or drug-induced overweight/obesity.
   2. Type 1 or type 2 diabetes mellitus, or laboratory evidence of diabetes (HbA1c ≥6.5%, fasting plasma glucose ≥7.0 mmol/L, or random/2-hour OGTT plasma glucose ≥11.1 mmol/L).
   3. Acute or chronic pancreatitis or pancreatic injury.
   4. Gallstones or cholecystitis, except adequately treated cases without residual disease.
   5. Medullary thyroid carcinoma, MEN 2A/2B, or relevant family history.
   6. Previous bariatric surgery or planned procedures that may significantly affect body weight.
   7. Moderate or severe depression, PHQ-9 score ≥15, severe psychiatric disorders, suicidal ideation/behavior, or suicide risk.
   8. Malignancy within 5 years, except specified adequately treated localized cancers.
   9. Significant cardiovascular or cerebrovascular disease within 6 months before screening/randomization.
   10. Osteoporosis defined as T-score ≤-2.5 or Z-score ≤-2.0, as applicable.
   11. Uncontrolled hypertension (SBP ≥160 mmHg and/or DBP ≥100 mmHg).
   12. Clinically significant thyroid dysfunction.
   13. Significant gastric emptying disorders or active gastrointestinal disease.
   14. History of organ transplantation or awaiting transplantation.
   15. Autoimmune diseases likely to require systemic glucocorticoids.
   16. Current participation in an active weight-loss program not yet in the maintenance phase.