Phase 1 Clinical Study of MWN110 Injection in Healthy Participants and Overweight or Obese Participants

A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Subcutaneous Administrations of MWN110 Injection in Healthy Participants and Overweight or Obese Participants

This study is a multicenter, randomized, double-blind, placebo-controlled, single and multiple ascending-dose phase 1 clinical trial aimed at evaluating the safety, tolerability, PK, PD, and immunogenicity of MWN110 Injection in healthy participants and overweight or obese participants.

The study consists of two parts: Part 1, a single ascending dose (SAD) study in healthy participants with 8 dose cohorts; and Part 2, a multiple ascending dose (MAD) study in overweight or obese participants with 3 dose cohorts, with a dosing frequency of once weekly or once every 4 weeks.

Approximately 103 participants will be enrolled. The primary endpoint is safety and tolerability, assessed by adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram, and ophthalmic examination. Secondary endpoints include single-dose and multiple-dose PK parameters, PD parameters (body weight, BMI, waist circumference, muscle mass, body fat percentage, visceral fat, subcutaneous fat, bone mineral density), and immunogenicity (anti-drug antibodies).

Inclusion Criteria:

1. Male or female participants aged 18 to 65 years (inclusive) at the time of signing the informed consent form (ICF); the proportion of either gender shall not be less than 1/3.
2. Male participants with body weight not less than 50 kg, female participants with body weight not less than 45 kg; body mass index (BMI) within 20.0 to 40.0 kg/m^2 (inclusive).
3. Female participants must have no plans for pregnancy or egg donation from 14 days before the first dose to 6 months after the last dose and must agree to use effective contraceptive measures to avoid pregnancy; male participants must have no plans for fathering a child or sperm donation from the first dose to 6 months after the last dose and must agree to use effective contraceptive measures to avoid causing partner pregnancy.

Exclusion Criteria:

1. Known or suspected allergy to the investigational product or its excipients, or history of severe allergy (including any food or drug allergy).
2. Body weight change >5% within 3 months prior to screening (weight change % = [maximum weight in 3 months - minimum weight in 3 months] / maximum weight in 3 months x 100%).
3. Diagnosed with secondary overweight or obesity.
4. History of pancreatitis (chronic pancreatitis or idiopathic acute pancreatitis); serum amylase or lipase above the upper limit of normal.
5. Known history of disease or comorbidity affecting skeletal muscle protein.
6. At screening, the presence of active acne, pyogenic dermatosis, allergic dermatosis, inflammatory dermatosis, infectious dermatosis, unhealed skin wounds, extensive skin lesions, or skin abnormalities such as vegetations or masses, judged by the investigator as unsuitable for participation.
7. History of infectious disease within 4 weeks prior to screening (judged by the investigator as potentially significantly affecting safety evaluation), history of severe trauma, or history of major surgery within 3 months, or planned surgery during the study period.
8. At screening, any laboratory test meeting any of the following criteria: a) fasting blood glucose >6.1 mmol/L or <3.9 mmol/L; b) alanine aminotransferase, aspartate aminotransferase, or total bilirubin >1.5 × upper limit of normal (ULN); c) estimated glomerular filtration rate <70 mL/min/1.73 m² (CKD-EPI equation) or urinary protein positive (1+ or above); d) fasting triglycerides ≥3.42 mmol/L (Part 1) or >5.64 mmol/L (Part 2); e) hemoglobin <100 g/L (females) or <110 g/L (males); f) blood uric acid (UA) >540 μmol/L.
9. At screening, 12-lead electrocardiogram showing heart rate <50 bpm or >100 bpm, second-degree or third-degree atrioventricular block, long QT syndrome, or QTcF >460 ms (female) or >450 ms (male), or other electrocardiogram abnormalities judged by the investigator as requiring pharmacological intervention.
10. Participants who have undergone dieting or weight-loss treatment within 30 days prior to the first dose, or who have experienced major changes in lifestyle habits.
11. Use of GLP-1 receptor agonists, weight-loss drugs, systemic corticosteroids (oral or intravenous for more than 7 days), or psychiatric medications within 3 months before the first dose.
12. Engaged in strenuous muscle exercise, high-intensity resistance training, or regular muscle-strengthening activities within 30 days before the first dose.