Phase 2 Clinical Study of MWX203 Injection Alone or in Combination With Inclisiran Sodium Injection in Patients With Mixed Dyslipidemia

Inclusion criteria

• Male or female participants aged 18 to 75 years (inclusive) at the time of signing the informed consent form (ICF).
• On stable-dose statin therapy (moderate-intensity or above: atorvastatin 10-40 mg, rosuvastatin 5-20 mg, fluvastatin 80 mg, lovastatin 40 mg, pitavastatin 1-4 mg, pravastatin 40 mg, simvastatin 20-40 mg, or Xuezhikang 1.2 g daily) for at least 4 weeks prior to screening, and willing to maintain stable statin use (without changing the type or dose) during the study.
• Fasting LDL-C at screening and during run-in meets one of the following criteria (local laboratory): ASCVD very-high risk: LDL-C ≥ 1.4 mmol/L (54 mg/dL); ASCVD high risk: LDL-C ≥ 1.8 mmol/L (70 mg/dL); ASCVD moderate-to-high risk: LDL-C ≥ 2.6 mmol/L (100 mg/dL); ASCVD low risk: LDL-C ≥ 3.4 mmol/L (130 mg/dL).
• Fasting TG at screening and during run-in ≥ 1.70 mmol/L (150 mg/dL) and ≤ 5.6 mmol/L (500 mg/dL) (local laboratory).
• Participants or their partners have no plans for pregnancy or sperm/egg donation from the time of signing the informed consent form (ICF) until at least 6 months after the last dose and agree to use medically recognized, effective non-pharmacological contraceptive methods throughout the study.
• Participants voluntarily agree to participate in the study, are willing to comply with the protocol-required visit schedule and study procedures, and provide written informed consent.

Exclusion criteria

• Confirmed diagnosis of homozygous familial hypercholesterolemia (HoFH).
• History of active pancreatitis within 12 weeks prior to screening.
• Severe cardiovascular or cerebrovascular disease within 24 weeks prior to screening or during the run-in period (e.g., hypertensive encephalopathy, transient ischemic attack, severe arrhythmia such as recurrent symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular rate, or NYHA Class III-IV heart failure); severe aortic/coronary/peripheral vascular disease; or conditions requiring surgical intervention.
• Acute ischemic ASCVD event within 48 weeks prior to screening or during the run-in period (e.g., acute coronary syndrome, ischemic stroke); or history of hemorrhagic stroke.
• Percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or peripheral arterial revascularization performed within 48 weeks prior to screening, or planned to be performed during the study period.
• Uncontrolled hypertension at screening or during run-in: systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg despite no treatment or at least 4 weeks of stable antihypertensive therapy.
• Significant thyroid disease at screening, except for participants receiving stable-dose thyroid hormone replacement or antithyroid therapy for at least 12 weeks prior to screening.
• Poorly controlled type 2 diabetes mellitus at screening (HbA1c > 8.5%), or prior diagnosis of type 1 diabetes mellitus.
• Serious infection within 4 weeks prior to screening or during run-in, as judged by the investigator to potentially affect protocol compliance or interfere with study results.
• Use of any lipid-lowering drug within 4 weeks prior to screening (except for statins administered at a stable dose for at least 4 weeks before screening), or drugs/health products with lipid-regulating effects as judged by the investigator, including but not limited to cholesterol-absorption inhibitors, fibrates, red-yeast-rice-containing products, niacin, omega-3 fatty acids, stanols, or bile-acid sequestrants.
• Use of ANGPTL3 inhibitors within 1 year prior to screening.
• Use of PCSK9 inhibitors within 180 days prior to screening.
• Use of any liver-targeted small nucleic-acid therapeutics within 1 year prior to screening.
• Laboratory findings at screening or during run-in meeting any of the following criteria (repeat testing is permitted at screening with documented rationale by the investigator): platelet count ≤ 100 × 10⁹/L; HbA1c > 8.5% (local laboratory); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × ULN; total bilirubin > 1.5 × ULN (> 3 × ULN for participants with a history of Gilbert's syndrome); creatine kinase (CK) > 3 × ULN; TSH below the lower limit of normal (LLN) or > 1.5 × ULN at screening.
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² at screening or during run-in (calculated using the 2021 CKD-EPI equation).
• Left ventricular ejection fraction (LVEF) < 30% on echocardiography at screening.
• Body-weight change ≥ 10% (gain or loss) within 3 months prior to screening, or planned weight-loss intervention during the study.
• Major lifestyle changes within 4 weeks prior to screening, or inability to comply with dietary control requirements during the study.
• Any other condition that, in the investigator's opinion, makes the participant unsuitable for this trial.