A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Subcutaneous Administration of MWN117 Injection in Healthy and Obese Participants
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
This study is a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MWN117 injection in healthy and obese Chinese participants.
The study consists of two parts. Part A includes two dose cohorts enrolling healthy participants, and Part B includes four dose cohorts enrolling obese participants. A total of 48 participants will be enrolled. Within each dose cohort, participants will be randomly assigned to receive a single subcutaneous injection of MWN117 or matching placebo.
The primary endpoint is safety, assessed by adverse events and related examinations. Secondary endpoints include plasma pharmacokinetic (PK) parameters and urine PK parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 18 to 55 years (inclusive) at the time of informed consent signing; male or female.
- •Body mass index (BMI): Part A, healthy participants, 20.0-27.9 kg/m² (inclusive); Part B, obese participants, 28.0-35.0 kg/m² (inclusive), with body weight > 60 kg for males and > 50 kg for females.
- •Stable weight for 3 months prior to screening (self-reported weight change ≤ 5%), with no major changes in diet or physical activity, and the ability to maintain a stable lifestyle during the study.
- •Participants and their sexual partners must have no plans for pregnancy or sperm/oocyte donation from the time of ICF signing until at least 12 months post-dose; participants must use effective non-pharmacological contraception during this period. Female participants of childbearing potential must have a negative serum pregnancy test at screening.
排除标准
- •Use of GLP-1 receptor agonists (e.g., liraglutide, semaglutide, tirzepatide) within 3 months prior to screening.
- •Use of medications significantly affecting body weight within 3 months prior to screening, including but not limited to: orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion, weight-affecting herbal products, or meal replacements; cumulative or continuous use of systemic steroids ≥ 14 days (IV/oral), tricyclic antidepressants, psychiatric medications, or sedatives (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid, lithium).
- •Endocrine disorders that may significantly affect body weight (e.g., Cushing's syndrome, hypothyroidism, or hyperthyroidism), or drug-induced, monogenic, or genetic obesity syndromes.
- •History of surgery or device treatment for overweight or obesity.
- •Diagnosis of type 1 or type 2 diabetes, or laboratory findings suggesting diabetes during screening (HbA1c ≥ 6.5%, fasting serum glucose ≥ 7.0 mmol/L, or random glucose ≥ 11.1 mmol/L).
- •Clinically significant laboratory abnormalities at screening: a) ALT, AST, GGT, or TBIL > 1.5 × ULN; b) Serum Cr > 1.2 × ULN or eGFR < 80 mL/min/1.73 m²; c) Fasting TG > 5.65 mmol/L (500 mg/dL).
- •12-lead ECG abnormalities at screening: a) PR interval ≥ 210 ms; b) QRS duration ≥ 120 ms; c) QTcF > 450 ms (males) or > 470 ms (females); d) Any other clinically significant ECG abnormality as judged by the investigator.
- •Use of liver-targeted antisense oligonucleotides (ASO) or small interfering RNA (siRNA) drugs within 12 months prior to screening.
- •History of hypersensitivity to any component of MWN117, other siRNA drugs, or GalNAc-conjugated drugs; or allergy to two or more drugs or foods; or history of severe allergic reactions.
研究组 & 干预措施
Part A
Part A consists of 2 dose groups. Healthy participants in all dose groups were randomly assigned to receive a single subcutaneous dose of MWN117 or placebo.
干预措施: MWN117 (Drug)
Part A
Part A consists of 2 dose groups. Healthy participants in all dose groups were randomly assigned to receive a single subcutaneous dose of MWN117 or placebo.
干预措施: Placebo (Drug)
Part B
Part B consists of 4 dose groups. Obese participants in all dose groups were randomly assigned to receive a single subcutaneous dose of MWN117 or placebo.
干预措施: MWN117 (Drug)
Part B
Part B consists of 4 dose groups. Obese participants in all dose groups were randomly assigned to receive a single subcutaneous dose of MWN117 or placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: Up to Day 169
The incidence of adverse Events (AEs) and serious adverse events (SAEs).
次要结局
- Time to Reach Maximum Plasma Concentration (Tmax)(Up to 48 hours post-dose)
- Area Under the Curve From Time 0 to the Last Measurable Time Point (AUC0-last)(Up to 48 hours post-dose)
- Area Under the Curve From Time 0 to Infinity (AUC0-inf)(Up to 48 hours post-dose)
- Maximum Plasma Concentration (Cmax)(Up to 48 hours post-dose)
- Elimination Half-Life (t1/2)(Up to 48 hours post-dose)
- Renal Clearance (CLr)(Up to 48 hours post-dose)
- Cumulative Excretion Amount (Ae)(Up to 48 hours post-dose)
- Cumulative Excretion Fraction (Fe)(Up to 48 hours post-dose)