Phase 1 Clinical Study of MWN105 Injection in Participants With Overweight or Obesity

A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Subcutaneous Administrations of MWN105 Injection in Chinese Non-Diabetic Participants With Overweight or Obesity

This study is a randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation phase I clinical trial aiming to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of MWN105 injection in Chinese non-diabetic overweight or obese participants.

The study plans to enroll 36 male and female participants. Three dose groups were preset, with 12 participants in each. They were randomly assigned to receive MWN105 injection or placebo at a ratio of 5:1 and were administered the treatment in a titration manner, once a week, with a dose increase every two weeks until reaching the target dose. The administration lasted for 8 weeks.

The study consists of a 2-week screening period, an 8-week administration/observation period, and a 4-week follow-up period, totaling 14 weeks. The primary endpoint is the incidence of adverse events. Secondary endpoints include pharmacokinetics, pharmacodynamics, and immunogenicity.

Inclusion Criteria:

1. Participants should be aged 18 to 50 years (inclusive, based on the date of signing the informed consent form) and be male or female, non-diabetic, overweight or obese individuals from China.
2. Obese individuals: BMI ≥ 28.0 kg/m²; overweight individuals: 24.0 kg/m² ≤ BMI < 28.0 kg/m², with or without the following: i. Complications including prediabetes (impaired fasting glucose and/or impaired glucose tolerance), hypertension, metabolic dysfunction-associated steatotic liver disease, or dyslipidemia; ii. Weight-bearing joint pain; iii. Breathing difficulties caused by obesity or obstructive sleep apnea syndrome.
3. Female participants must have no plans for pregnancy or egg donation from 14 days before the first administration until 4 months after the last administration, and must voluntarily use effective contraception. Male participants must have no plans for sperm donation from the first administration until 4 months after the last administration and must voluntarily use effective contraception to prevent partner pregnancy.

Exclusion Criteria:

1. Individuals with a history of severe drug allergy, concurrent severe allergic diseases, or a severe allergic constitution.

2. Individuals with a history or evidence of any of the following:

   • Secondary or drug-induced obesity.
   • Type 1 or type 2 diabetes.
   • Acute or chronic pancreatitis or pancreatic injury.
   • Medullary thyroid carcinoma, MEN type 2A or 2B, or a related family history.
   • Prior gastric weight-loss surgery, or liposuction/fat removal surgery within one year before screening.
   • Plans to undergo weight-loss surgery, liposuction, or abdominal fat removal surgery during the study period that would significantly affect body weight.
   • History of depression or other serious mental illness, or history of suicidal ideation or behavior.
   • History of malignant tumors.
   • History of any of the following heart diseases within 6 months before screening: decompensated heart failure, unstable angina pectoris, myocardial infarction, coronary artery bypass grafting, or coronary stent implantation; history of hemorrhagic or ischemic stroke within 6 months before screening, who were assessed by the investigator as unsuitable for the trial.
   • Severe or recurrent symptomatic hypoglycemia within 6 months before screening.
   • Untreated hypertension at screening that is not stabilized by treatment (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg), or hypertension reaching these levels despite treatment at the time of screening.
   • History of other severe endocrine system diseases affecting glucose metabolism.
   • History of digestive system diseases that may increase participant risk, such as acute or chronic cholecystitis; symptomatic or treated cholelithiasis or gallbladder polyps at the time of screening; history of chronic gastrointestinal diseases; gastrointestinal surgery within 12 weeks before screening, who were assessed by the investigator as unsuitable for the trial.
   • A history of infectious diseases, severe trauma, or major surgery within 4 weeks before screening, who were assessed by the investigator as unsuitable for the trial.

3. Use of any of the following medications or treatments:

   • Use of GLP-1 receptor agonists or drugs targeting the same target within 12 weeks prior to screening.
   • Use of systemic glucocorticoids within 12 weeks prior to screening.
   • Use of tricyclic antidepressants, psychiatric medications, or sedative drugs that significantly affect body weight within 12 weeks prior to screening.
   • Use of prescription drugs for weight control within 12 weeks prior to screening.
   • Use of over-the-counter drugs, health supplements, herbal preparations, or meal replacement products for weight control, appetite reduction, or as an alternative to diet within 12 weeks prior to screening, if used for a long-term period (continuous for ≥4 weeks or cumulative for ≥6 weeks).
   • Use of acupuncture, physical therapy, or other non-drug treatments for weight loss within 12 weeks prior to screening.
   • Regular use of drugs for gastrointestinal motility or drugs for irritable bowel syndrome, or use of any dosage of laxatives, within 4 weeks prior to screening.