Phase 1 Clinical Study of MWN117 Injection in Healthy Participants and Participants With Obesity

Korábbi kezelés

• 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).
• Use of liver-targeted antisense oligonucleotides (ASO) or small interfering RNA (siRNA) drugs within 12 months prior to screening.

Más betegség

• 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.
• 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.

Laborértékek

• 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).

Egyéb

• 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.

• 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.