MASH - Metabolic Dysfunction-Associated Steatohepatitis, Overweight , Obesity, Type 2 Diabetes Mellitus (T2DM)
Conditions
Brief summary
This study is a randomized, double-blind, placebo-controlled, single-dose and multiple-dose, dose-escalation phase I clinical trial, aiming to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics, and immunogenicity of MWN105 injection in healthy Chinese volunteers, and to provide a reference for the next clinical trial. This study includes a single ascending dose (SAD) study and a multiple ascending dose (MAD) study. The SAD study consists of 4 dose groups; the MAD study consists of 2 dose groups and adopts a 4-week dose titration scheme. The study plans to enroll 55 volunteers. The primary endpoint is the incidence of adverse events. The secondary endpoints are the pharmacokinetic and pharmacodynamic characteristics and immunogenicity endpoints.
Interventions
DRUGMWN105
S1, S2 S3, S4; administered subcutaneously (SC)
DRUGPlacebo
administered SC
Sponsors
Shanghai Minwei Biotechnology Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. The selected subjects should be healthy male or female individuals aged 18 to 45 years (inclusive). 2. Female subjects should have a body weight of at least 50.0 kg, and male subjects should have a body weight of at least 55.0 kg. Their body mass index (BMI) should be within the range of 19.0-28.0 kg/m² (inclusive). 3. Physical examination, vital signs, 12-lead electrocardiogram (ECG), abdominal ultrasound, and clinical laboratory test results (including serum calcitonin, coagulation function, and thyroid function) should show no clinically significant abnormalities. 4. Subjects are required to abstain from sexual activity or use two effective contraceptive methods simultaneously starting from 1 month before screening through 6 months after the last administration, and must have no plans for sperm or egg donation.
Exclusion criteria
1. Any history of clinical severe diseases or current presence of any clinically significant diseases. 2. Those with a known history or family history of medullary thyroid carcinoma, type 2 multiple endocrine neoplasia syndrome (MEN2), or those with a history of hypothyroidism or abnormal thyroid hormone levels. 3. Subjects with a history of acute or chronic pancreatitis, symptomatic gallbladder disease, history of pancreatic injury, or other high-risk factors that may cause pancreatitis, or those with an amylase level \> 1.5 times the upper limit of the normal range (ULN) during screening. 4. Those with clinically significant gastric emptying abnormalities (such as gastric outlet obstruction), severe chronic gastrointestinal diseases (such as having had active ulcers within 6 months), long-term use of drugs that directly affect gastrointestinal motility (including but not limited to mosapride, cispamide), or those who have undergone gastrointestinal surgery within 12 weeks before screening and are assessed by the investigator as not suitable to participate in this clinical study. 5. Used any prescription drugs, herbal medicines, over-the-counter drugs, or dietary supplements within 2 weeks before administration. 6. Had an infectious disease within 4 weeks before screening, severe trauma, or a history of major surgery. 7. Received vaccines or planned to receive vaccines during the trial screening. 8. Donated blood, experienced significant blood loss (\> 450 mL), or received a blood transfusion within 12 weeks before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) | From Day 1 to Day 50 | The incidence of adverse events (AEs) and serious adverse events (SAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in C-peptide over time | Baseline, Day 29, Day 50 | — |
| Detect anti-drug antibodies (ADA) and their titers | Baseline, Day 29, Day 50 | — |
| Maximum Concentration (Cmax) | From Day 1 to Day 29 | Cmax of MWN105. |
| Time to Reach Maximum Concentration (Tmax) | From Day 1 to Day 29 | Tmax of MWN105. |
| Area Under the Curve From Time 0 to Last Quantifiable Time Point (AUC0-t) | From Day 1 to Day 29 | AUC0-t of MWN105. |
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) | From Day 1 to Day 29 | AUC0-inf of MWN105. |
| Elimination Half-Life (t1/2) | From Day 1 to Day 29 | t1/2 of MWN105. |
| Steady State Maximum Concentration (Cmax,ss) | From Day 1 to Day 50 | Cmax,ss of MWN105. |
| Time to Reach Maximum Concentration at Steady State (Tmax,ss) | From Day 1 to Day 50 | Tmax,ss of MWN105. |
| Steady State Area Under the Curve From Time 0 to Last Quantifiable Time Point (AUC0-t,ss) | From Day 1 to Day 50 | AUC0-t,ss of MWN105. |
| Steady State Area Under the Curve from time zero to infinity (AUC0-inf,ss) | From Day 1 to Day 50 | AUC0-inf,ss of MWN105. |
| Steady State Apparent Terminal Elimination Half-life (t1/2,ss) | rom Day 1 to Day 50 | t1/2,ss of MWN105. |
| Change from baseline in body weight over time | Baseline, Day 29, Day 50 | — |
| Change from baseline in body mass index (BMI) over time | Baseline, Day 29, Day 50 | — |
| Change from baseline in waist circumference over time | Baseline, Day 29, Day 50 | — |
| Change from baseline in hip circumference over time | Baseline, Day 29, Day 50 | — |
| Change from baseline in fasting blood glucose over time | Baseline, Day 29, Day 50 | — |
| Change from baseline in waist-to-hip ratio over time | Baseline, Day 29, Day 50 | — |
Countries
China
Outcome results
None listed