Hyperlipidemias
Conditions
Keywords
Low-density lipoprotein cholesterol, PCSK9, SAL003
Brief summary
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.
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.
Interventions
DRUGSAL003 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.
DRUGPlacebo
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.
Sponsors
Salubris (Chengdu) Biotechnology Co., Ltd.
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change of Low-Density Lipoprotein Cholesterol (LDL-C). | at Week 12 | Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12. |
Countries
China
Outcome results
None listed