Eligible participants were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 150 mg Q2W, tafolecimab 450 mg Q4W, placebo Q2W or placebo Q4W, respectively, in the 12-week double-blind treatment period. Randomization was implemented by an interactive web response system and was stratified by LDL-C levels at screening (≥ or < 4.8 mmol/L), by baseline ezetimibe use (yes/no) and by prior use of PCSK9 inhibitors (yes/no). The participants, investigators and study site personnel involved in treating and assessing participants were masked to treatment allocations.
After the 12-week double-blind treatment period, participants receiving tafolecimab continued to receive open-label tafolecimab with the previous regimens while participants receiving placebo Q2W or Q4W crossed over to receive open-label tafolecimab 150 mg Q2W or 450 mg Q4W, respectively, for 12 weeks, followed by an 8-week safety follow-up.
Fasting LDL-C (OSR6183, Beckman Coulter), HDL cholesterol (HDL-C, OSR6187, Beckman Coulter), total cholesterol (OSR6116, Beckman Coulter) and triglycerides (OSR61118, Beckman Coulter) concentrations were measured by commercial kits on a Beckman Coulter AU600 Chemistry Analyzer. Non-HDL cholesterol (non-HDL-C) concentration was calculated by subtracting HDL-C concentration from total cholesterol concentration. Very low density lipoprotein cholesterol (vLDL-C) concentration was calculated by dividing the triglyceride concentration by 5 (when triglyceride < 4.52 mmol/L) or by subtracting HDL-C and LDL-C concentration from total cholesterol concentration (when triglyceride ≥4.52 mmol/L). Apolipoprotein A1, apolipoprotein B and lipoprotein(a) concentrations were determined using a nephelometric method (OUED, OSAN and OQHL, respectively, Siemens BN ProSpec System). We measured unbound PCSK9 concentrations using an in-house developed enzyme-linked immunosorbent assay. All lipids and PCSK9 were tested in a central laboratory (WuXi AppTec, Shanghai).
DNA extracted from blood samples of all enrolled participants were sequenced by Novogene (Beijing) for variants in all exons of LDLR, APOB, PCSK9 and LDLRAP1 gene. Pathogenicity of variants were annotated using clinical classification of the Leiden Open Variation Database (LOVD) [17 (link)].
After the 12-week double-blind treatment period, participants receiving tafolecimab continued to receive open-label tafolecimab with the previous regimens while participants receiving placebo Q2W or Q4W crossed over to receive open-label tafolecimab 150 mg Q2W or 450 mg Q4W, respectively, for 12 weeks, followed by an 8-week safety follow-up.
Fasting LDL-C (OSR6183, Beckman Coulter), HDL cholesterol (HDL-C, OSR6187, Beckman Coulter), total cholesterol (OSR6116, Beckman Coulter) and triglycerides (OSR61118, Beckman Coulter) concentrations were measured by commercial kits on a Beckman Coulter AU600 Chemistry Analyzer. Non-HDL cholesterol (non-HDL-C) concentration was calculated by subtracting HDL-C concentration from total cholesterol concentration. Very low density lipoprotein cholesterol (vLDL-C) concentration was calculated by dividing the triglyceride concentration by 5 (when triglyceride < 4.52 mmol/L) or by subtracting HDL-C and LDL-C concentration from total cholesterol concentration (when triglyceride ≥4.52 mmol/L). Apolipoprotein A1, apolipoprotein B and lipoprotein(a) concentrations were determined using a nephelometric method (OUED, OSAN and OQHL, respectively, Siemens BN ProSpec System). We measured unbound PCSK9 concentrations using an in-house developed enzyme-linked immunosorbent assay. All lipids and PCSK9 were tested in a central laboratory (WuXi AppTec, Shanghai).
DNA extracted from blood samples of all enrolled participants were sequenced by Novogene (Beijing) for variants in all exons of LDLR, APOB, PCSK9 and LDLRAP1 gene. Pathogenicity of variants were annotated using clinical classification of the Leiden Open Variation Database (LOVD) [17 (link)].
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