This randomized study is to assess LDL-C reductions at Week 12 with monthly (Q4W \[≤31 days\]) dosing of HST101 (lerodalcibep) 300 mg administered subcutaneously (SC) compared to placebo in patients with atherosclerotic cardiovascular disease (ASCVD) or very-high/high risk for ASCVD including Heterozygous familial hypercholesterolemia (HeFH) on a stable diet and oral LDL-C lowering drug therapy, followed by 36-week open-label treatment with subsequent 4-week follow-up for total 52-week long-term safety and efficacy evaluation.
Provision of written and signed informed consent form prior to any study-specific procedure;
Male or female participants ≥18 years of age at the screening visit;
Body weight ≥ 40 kg and body mass index (BMI) ≥18 and ≤35 kg/m2;
On a stable diet and lipid-lowering oral drugs (such as statins, ezetimibe or Hybutimibe, omega-3 compounds, fenofibrate, nicotinic acid, etc.) for at least 4 weeks prior to the first drug administration
Documented history of homozygous familial hypercholesterolemia (HoFH);
Estimated glomerular filtration rate (eGFR)<30 mL/min/1.73m2;
Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST >2.5 × ULN at screening;
Poorly controlled thyroid disorder including hypothyroidism or hyperthyroidism;
Parallel
Lerodalcibep
DrugPCSK9 inhibitor
matching placebo
Drugplacebo
LDL-C change compared to Placebo
Percent change in LDL-C level from baseline (calculated by Friedewald formula) compared to Placebo
Mean LDL-C change at Weeks 10 and 12 compared to Placebo
Percent change in mean LDL-C level from baseline (calculated by Friedewald formula) compared to placebo at Weeks 10 and 12
LDL-C change over time
Absolute and percent change in LDL-C level from baseline at Weeks 4, 8, 10, and 12
Free PCSK9 change
Absolute and Percent change in serum free PCSK9 level from baseline at Weeks 4,8 and 12
Other Lipid parameters change
Absolute and Percent change in TC, TG, HDL-C, non-HDL-C, VLDL-C, Apo B and Lp(a) from baseline at Weeks 4,8 and 12
Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline
To assess the effect of HST101 on the percentage of patients achieving LDL-C\<2.6 mmol/L (high-risk for ASCVD patients), LDL-C\<1.8 mmol/L and \>50% reduction from baseline (very-high risk for ASCVD patients), LDL-C\<1.4 mmol/L and \>50% reduction from baseline (ultra-high risk for ASCVD patients)
Long time free PCSK9 change
Absolute and percent change in serum free PCSK9 levels from baseline at Weeks 16,20,24,36,48 and 52
Long time LDL-C change
Absolute and percent change in LDL-C level from baseline at Weeks 16,20,22,24,36,48,50 and 52
Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline
To assess the effect of HST101 on the percentage of patients achieving LDL-C\<2.6 mmol/L (high-risk for ASCVD patients), LDL-C\<1.8 mmol/L and \>50% reduction from baseline (very-high risk for ASCVD patients), LDL-C\<1.4 mmol/L and \>50% reduction from baseline (ultra-high risk for ASCVD patients) at Weeks 16, 20, 24, 36, 48 and 52
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