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

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study to Evaluate the Efficacy and Safety of MWX203 Injection Alone or in Combination With Inclisiran Sodium Injection in Participants With Mixed Dyslipidemia and Inadequate Lipid Control

This is a multicenter, randomized, blinded, placebo-controlled Phase 2 study designed to preliminarily evaluate the efficacy, safety, pharmacokinetic (PK), and immunogenicity profiles of MWX203 Injection alone or in combination with Inclisiran Sodium Injection in participants with mixed dyslipidemia who have inadequate lipid control despite stable statin therapy.

The study includes 5 parallel arms with a planned enrollment of 216 Chinese participants. The study drug is administered subcutaneously once every 12 weeks for a total of 2 doses. The double-blind treatment period lasts 36 weeks, and participants whose lipid levels do not return to baseline will enter a 12-week extended follow-up period. The primary endpoint is the percentage change in serum triglyceride (TG) level from baseline at Week 24.

Inclusion Criteria:

1. Male or female participants aged 18 to 75 years (inclusive) at the time of signing the informed consent form (ICF).
2. 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.
3. 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).
4. 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).
5. 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.
6. 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:

1. Confirmed diagnosis of homozygous familial hypercholesterolemia (HoFH).
2. History of active pancreatitis within 12 weeks prior to screening.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Poorly controlled type 2 diabetes mellitus at screening (HbA1c > 8.5%), or prior diagnosis of type 1 diabetes mellitus.
9. 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.
10. 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.
11. Use of ANGPTL3 inhibitors within 1 year prior to screening.
12. Use of PCSK9 inhibitors within 180 days prior to screening.
13. Use of any liver-targeted small nucleic-acid therapeutics within 1 year prior to screening.
14. 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.
15. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² at screening or during run-in (calculated using the 2021 CKD-EPI equation).
16. Left ventricular ejection fraction (LVEF) < 30% on echocardiography at screening.
17. Body-weight change ≥ 10% (gain or loss) within 3 months prior to screening, or planned weight-loss intervention during the study.
18. Major lifestyle changes within 4 weeks prior to screening, or inability to comply with dietary control requirements during the study.
19. Any other condition that, in the investigator's opinion, makes the participant unsuitable for this trial.