Phase 1 Clinical Study of MWX203 Injection in Healthy Subjects

A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Subcutaneous Administration of MWX203 Injection in Healthy Chinese Subjects

This is a randomized, double-blind, placebo-controlled, single ascending dose Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of MWX203 Injection in healthy Chinese subjects.

The study comprises six dose cohorts with a planned enrollment of 54 subjects. The primary endpoint is safety, assessed by adverse events (AEs), serious adverse events (SAEs), vital signs, physical examinations, laboratory tests, and 12-lead electrocardiograms. Secondary endpoints include plasma PK parameters, urinary PK parameters, and immunogenicity (anti-drug antibodies).

Inclusion Criteria:

1. Healthy male and female subjects aged 18 to 55 years (inclusive) at the time of signing the informed consent form (ICF).
2. Fasting serum LDL-C ≥ 2.6 mmol/L (100 mg/dL) and < 4.1 mmol/L (158 mg/dL), and fasting triglycerides ≥ 1.1 mmol/L (100 mg/dL) and < 5.7 mmol/L (500 mg/dL) at screening; no lipid-regulating drugs used within the past 3 months.
3. Body mass index (BMI) from 19.0 to 30.0 kg/m², inclusive, at screening; male subjects must have a body weight ≥ 50.0 kg and female subjects must have a body weight ≥ 45.0 kg.
4. Stable diet and physical-activity habits for 4 weeks prior to screening; no major changes to diet or exercise are planned during the study, and participants will not follow any weight-loss plan.
5. Subjects or their partners have no plans for pregnancy, sperm donation, or egg donation from the time of signing the ICF until at least 6 months after dosing, and agree to use medically-recognized, effective non-pharmacological contraceptive methods throughout the study.
6. Voluntarily participate in the study; able to read, understand, and sign the ICF before study participation; willing to comply with the study protocol and expected to complete the study.

Exclusion Criteria:

1. Any infectious disease within 4 weeks prior to screening (as judged by the investigator to affect the subject's ability to participate in the study).
2. Serious trauma or major surgery (requiring general anesthesia) within 6 months prior to screening, or planned major surgery during the study.
3. At screening, any of the following laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or total bilirubin > 1.5 × ULN; serum creatinine > 1.2 × ULN; or estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m² (calculated using the CKD-EPI equation, Appendix 4).
4. QTcF ≥ 450 ms (male) or ≥ 470 ms (female) at screening; or clinically-significant abnormalities on the 12-lead electrocardiogram.
5. HbA1c > ULN.
6. Overall atherosclerotic cardiovascular disease (ASCVD) risk assessed by the investigator as moderate or high risk at screening.
7. Use of any liver-targeted oligonucleotide drug within 1 year prior to screening.
8. Pregnant or lactating female subjects at screening.
9. Difficult venous access, difficult subcutaneous injection, or intolerance to repeated venipuncture; or clinically significant needle phobia or blood phobia history as judged by the investigator.
10. Use of any over-the-counter medications, prescription medications, traditional Chinese medicine, vitamins, or health supplements within 2 weeks prior to screening or within 5 half-lives of any prior medication (whichever is longer).
11. Receipt of any live vaccine, live attenuated vaccine, or vaccines containing live viral components within 3 months prior to screening or planned vaccination during the study.
12. Any other condition judged by the investigator to make the subject unsuitable for participation in this study.