MASH - Metabolic Dysfunction-Associated Steatohepatitis, Overweight , Obesity, Type 2 Diabetes Mellitus (T2DM)
Conditions
Brief summary
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.
Interventions
Sponsors
Shanghai Minwei Biotechnology Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | From Day 1 to Day 78 | Safety and tolerability assessed by the incidence of AEs and SAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in waist circumference over time | Baseline, Day 78 | Change in waist circumference from baseline to Day 78. |
| Change from baseline in lipid profile over time | Baseline, Day 78 | Change in lipid parameters (including total cholesterol, LDL-C, HDL-C, triglycerides) from baseline to Day 78. |
| Detect anti-drug antibodies (ADA) | Baseline, Day 78 | — |
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) | From Day 1 to Day 78 | AUC0-inf of MWN105. |
| Elimination Half-Life (t1/2) | From Day 1 to Day 78 | t1/2 of MWN105. |
| Change from baseline in body weight over time | Baseline, Day 78 | Change in body weight from baseline to Day 78. |
| Maximum Concentration (Cmax) | From Day 1 to Day 78 | Cmax of MWN105. |
| Time to Reach Maximum Concentration (Tmax) | From Day 1 to Day 78 | Tmax of MWN105. |
| Change from baseline in body mass index (BMI) over time | Baseline, Day 78 | Change in BMI from baseline to Day 78. |
| Area Under the Curve From Time 0 to Last Quantifiable Time Point (AUC0-t) | From Day 1 to Day 78 | AUC0-t of MWN105. |
Countries
China
Contacts
CONTACTWanxiang Chen
Outcome results
None listed