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.

Study Overview

• Status: Completed
• Conditions: Hyperlipidemias
• Intervention / Treatment: Drug: SAL003 140 mg; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 618
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100083
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; Drug: SAL003 140 mg	Drug: SAL003 140 mg; Double-blind treatment period: Administer SAL003 140mg subcutaneously once every 4 weeks for a total of 3 times. Collect efficacy and safety results after 12 weeks. Extended administration period: Administer SAL003 140mg subcutaneously once every 4 weeks and follow up until 52 weeks to collect efficacy and safety results.
Placebo Comparator: Reference Group; Drug: Placebo	Drug: Placebo; Double-blind treatment period: Administer Placebo subcutaneously once every 4 weeks for a total of 3 times. Collect efficacy and safety results after 12 weeks. Extended administration period: Administer SAL003 140mg subcutaneously once every 4 weeks and follow up until 52 weeks to collect efficacy and safety results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change of Low-Density Lipoprotein Cholesterol (LDL-C).	Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12.	at Week 12

Collaborators and Investigators

• Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.
• Collaborators: Salubris (Chengdu) Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2023
• Primary Completion (Actual): April 22, 2025
• Study Completion (Actual): May 8, 2025

Study Registration Dates

• First Submitted: December 7, 2025
• First Submitted That Met QC Criteria: December 7, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 7, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: PCSK9; Low-density lipoprotein cholesterol; SAL003
• Additional Relevant MeSH Terms: Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Hyperlipidemias
• Other Study ID Numbers: SAL003A301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No