Hyperlipidemias, Hypercholesterolemia, Mixed Dyslipidemia
Conditions
Keywords
Low-density lipoprotein cholesterol, PCSK9, SAL003
Brief summary
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Study to Evaluate the Safety and Efficacy of Recombinant Fully Human Anti-PCSK9 Monoclonal Antibody Injection (SAL003) in Combination with Statin Therapy in Patients with Hypercholesterolemia and Mixed Dyslipidemia.
Detailed description
This is a Phase III, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of SAL003, a recombinant fully human anti-PCSK9 monoclonal antibody, in Chinese patients with hypercholesterolemia and mixed dyslipidemia at very high or high cardiovascular risk who have not achieved target LDL-C levels despite stable, moderate- to high-intensity statin therapy (with or without ezetimibe). Approximately 720 participants will be randomized in a 2:1 ratio to receive either SAL003 140 mg or matching placebo, administered subcutaneously every 4 weeks for 24 weeks. Following the double-blind period, all participants will enter an open-label extension period and receive SAL003 140 mg Q4W for an additional 28 weeks, with a total study duration of 52 weeks. The primary efficacy endpoint is the percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24. Key secondary endpoints include the absolute change in LDL-C, the proportion of subjects achieving LDL-C target levels, and changes in other lipid parameters.
Interventions
DRUGSAL003 140 mg
SAL003 140 mg
DRUGPlacebo
Placebo
Sponsors
Shenzhen Salubris Pharmaceuticals Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects aged 18 to 75 years. * On a stable, moderate- to high-intensity statin regimen (with or without ezetimibe) for at least 4 weeks prior to screening. * Fasting LDL-C above target levels per 2023 Chinese guidelines: With ASCVD history: ≥1.4 mmol/L (Extreme Risk) or ≥1.8 mmol/L (Very High Risk). Without ASCVD history: ≥2.6 mmol/L (Moderate/High Risk) or ≥3.4 mmol/L (Low Risk). Fasting triglycerides (TG) ≤ 5.6 mmol/L at screening/randomization. * Provide signed informed consent.
Exclusion criteria
* Homozygous Familial Hypercholesterolemia (HoFH). * Uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg). * Significant cardiovascular event (e.g., MI, unstable angina, stroke, PCI, CABG) within 3 months prior to screening. * Heart failure (NYHA Class III or IV) or LVEF \<40% within 3 months. * Severe renal impairment (eGFR \<30 mL/min/1.73m²). * Active liver disease or significant hepatic impairment (ALT/AST \>2.5x ULN or TBiL \>2x ULN). * Uncontrolled diabetes (HbA1c \>8.0%) or type 1 diabetes. * Use of other lipid-lowering therapies (e.g., fibrates, niacin) within 3 months or any PCSK9 inhibitor within 6 months prior to screening. * Known hypersensitivity to any component of the investigational product or other antibody therapies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change of LDL-C | at Week 24 | Percent change from baseline in LDL-C at Week 24. |
Countries
China
Outcome results
None listed