A Study of SAL003 in Participants With Hypercholesterolemia and Mixed Dyslipidemia

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Clinical Study to Evaluate the Safety and Efficacy of SAL003 Monotherapy in Participants With Hypercholesterolemia and Mixed Dyslipidemia

This is a Phase 3 study to evaluate the efficacy and safety of SAL003, a fully human monoclonal antibody against PCSK9, as monotherapy in Chinese participants with hypercholesterolemia and mixed dyslipidemia. Participants who are not on lipid-lowering therapy or have washed out from previous therapy will be randomized in a 2:1 ratio to receive either SAL003 140 mg or matching placebo, administered subcutaneously every 4 weeks for 12 weeks. Following the double-blind period, all participants will enter an open-label extension period and receive SAL003 140 mg Q4W for an additional 40 weeks. The primary objective is to demonstrate the superiority of SAL003 over placebo in reducing Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12.

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 clinical trial. The study consists of four periods: a Screening Period (up to 1 week), a Run-in Period (2 weeks), a Double-blind Treatment Period (12 weeks), and an Extended Treatment Period (40 weeks), with a total study duration of approximately 55 weeks per participant.

Approximately 600 participants will be randomized. Eligible participants must be aged 18-75 years with a fasting LDL-C level between 2.6 mmol/L and 4.9 mmol/L, who are either statin-naïve or have washed out from lipid-lowering drugs for at least 3 months. Key exclusion criteria include familial hypercholesterolemia, established atherosclerotic cardiovascular disease (ASCVD), uncontrolled hypertension, poorly controlled diabetes, and significant hepatic or renal impairment.

In the Double-blind Period, participants will be stratified by baseline LDL-C (<3.4 mmol/L or ≥3.4 mmol/L) and randomized to receive either SAL003 140 mg or placebo via subcutaneous injection every 4 weeks for 3 doses (Days 1, 29, and 57). After completing the 12-week double-blind period, all participants will enter the Extended Treatment Period and receive open-label SAL003 140 mg Q4W for 10 additional doses (from Week 12 to Week 52).

The primary efficacy endpoint is the percent change from baseline in LDL-C at Week 12. Key secondary endpoints include the change from baseline in LDL-C at Week 12, the proportion of participants achieving LDL-C target goals at Week 12 and Week 52, and the percent change from baseline in other lipid parameters (e.g., TC, TG, Non-HDL-C, ApoB) at Week 12 and Week 52. Safety, immunogenicity, and pharmacokinetics will be assessed throughout the study.

The primary analysis will be performed on the Full Analysis Set (FAS) using a repeated measures mixed-effects model (MMRM) to compare the least-squares mean difference between the SAL003 and placebo groups at Week 12.

Inclusion Criteria:

• Male or female, aged 18 to 75 years (inclusive).
• Fasting LDL-C ≥2.6 mmol/L and <4.9 mmol/L at screening/randomization.
• Meets criteria based on the 2023 Chinese Lipid Management Guidelines (e.g., specific LDL-C levels with certain risk factors, or presence of diabetes).
• Fasting triglycerides (TG) ≤5.6 mmol/L at screening/randomization.
• Provides written informed consent.

Exclusion Criteria:

• Diagnosis of familial hypercholesterolemia (HoFH or HeFH).
• History of atherosclerotic cardiovascular disease (ASCVD).
• Uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg).
• Type 1 diabetes or poorly controlled Type 2 diabetes (HbA1c >8.0%).
• Significant hepatic or renal impairment.
• Active liver disease or positive for HIV or Syphilis.
• History of malignancy within 5 years prior to screening.
• Use of any lipid-lowering drugs (statins, ezetimibe, etc.) or traditional Chinese medicines known to affect lipid metabolism within 3 months prior to screening.
• Prior treatment with any PCSK9 inhibitor.
• Known hypersensitivity to any component of the investigational product or history of severe allergy to antibody therapies.
• Any other condition deemed by the investigator to be unsuitable for participation.