Phase 2 Study to Evaluate the Efficacy and Safety of MWN109 Injection in Non-Diabetic Participants With Overweight

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial Assessing the Efficacy and Safety of MWN109 Injection in Non-Diabetic Participants With Overweight or Obesity

This study is a multicenter, randomized, double-blind, placebo-controlled phase II study conducted in China. It aims to evaluate the efficacy and safety of MWN109 injection in non-diabetic overweight or obese participants.

A total of 125 participants were enrolled in the study. All participants were randomly assigned using stratified block randomization by gender (male or female) and allocated to 4 treatment groups at a 1:1:1:1 ratio, with approximately 30 participants in each group. Each treatment group will reach the target dose through dose titration.

This study consists of a screening period of up to 2 weeks, a treatment period of 36 weeks, and a follow-up period of 4 weeks, totaling 42 weeks. The primary endpoint is the percentage change in body weight compared to the baseline after 36 weeks of drug administration. The secondary endpoints include the proportions of participants with a body weight reduction of ≥5%, ≥10%, ≥15%, and ≥20% relative to the baseline after 36 weeks of treatment, as well as the change in waist circumference relative to the baseline.

Inclusion Criteria:

1. Male or female individuals aged 18 to 65 years (inclusive), as determined by the date of signing the informed consent form;
2. Weight ≥ 70 kg (for males) or ≥ 60 kg (for females), with a body mass index (BMI) ≥ 30 kg/m² (obesity), or 27 kg/m² ≤ BMI < 30 kg/m² (overweight) and at least one weight-related comorbidity (such as hypertension, dyslipidemia, prediabetes, obstructive sleep apnea syndrome, metabolic dysfunction-associated steatotic liver disease, weight-bearing joint pain, cardiovascular diseases, polycystic ovary syndrome, etc.);
3. Resting heart rate ≥ 55 and ≤ 90 beats per minute (based on 12-lead electrocardiogram results during screening and before randomization);
4. Self-reported or documented weight control through diet and exercise for at least 12 weeks, with a weight change of less than 5.0% within the 12 weeks prior to screening;
5. No pregnancy plans from the date of signing the informed consent until 4 months after the last dose of the investigational drug; must voluntarily use effective contraception and have no plans for sperm or egg donation.

Exclusion Criteria:

1. It is known that the subject has an allergic constitution, or is allergic to any component of glucagon-like peptide-1 (GLP-1) receptor agonist drugs or investigational medicinal products, or has a severe allergic disease during screening, or has a history of severe drug allergy in the past;
2. 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;
3. 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;
4. It is known or discovered during screening that the electrocardiogram is abnormal and there is a significant safety risk, or further diagnosis and treatment are required, including but not limited to: arrhythmias that cannot be controlled or require drug treatment such as persistent ventricular tachycardia, second or third degree atrioventricular block, QTcF > 450 ms, long QT syndrome family history or Brugada syndrome family history, etc.
5. There is a history or evidence of any of the following diseases: secondary or drug-induced overweight or obesity; previous diagnosis of type 1 or type 2 diabetes, or at least one laboratory test indicator suggesting diabetes during screening; previous diagnosis of acute or chronic pancreatitis, or pancreatic injury; history of gallstones or cholecystitis during screening; previous diagnosis of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2A or 2B, or a related family history; previously undergone gastric weight loss surgery or other weight loss surgeries, or plans to undergo weight loss surgery, liposuction, abdominal lipolysis, or other surgeries that significantly affect body weight during the study period; previously had moderate or severe depression; diagnosed with a malignant tumor within the previous 5 years or evaluated as having potential malignant tumors during screening; history of any heart disease within 6 months before screening or before randomization; cerebrovascular accident within 6 months before screening or before randomization; uncontrolled hypertension during the screening period; history of hyperthyroidism or hypothyroidism, or clinically significant abnormal thyroid function test results during screening; clinically significant gastric emptying abnormalities, requires long-term use of drugs that directly affect gastrointestinal motility, or active gastrointestinal diseases during screening.