This study is being done to learn more about evolocumab in Chinese people with primary hypercholesterolemia or mixed dyslipidemia. This study will see if evolocumab will reduce low density lipoprotein cholesterol (LDL-C) in Chinese people who are also taking a certain type of lipid-lowering medication (statins with or without ezetimibe) and whether it causes any side effects.
This is a phase 3, multicenter, double-blind, randomized, placebo-controlled study of evolocumab in Chinese participants with hypercholesterolemia and mixed dyslipidemia. Participants who have signed the informed consent form (ICF) will have fasting lipids measured and all inclusion and exclusion criteria assessed. All eligible participants must be taking a maximum appropriate dose of an approved statin, not requiring up titration. Participants should maintain their current diet and exercise regimen. Treatment and follow-up period will be 12 weeks with an additional phone call or other participant contact at week 14 for those receiving investigational product every 2 weeks (Q2W). The end of study (EOS) for participants on once monthly (QM) investigational product is at the week 12 visit, which must be at least 30 days post last dose of investigational product. Evolocumab or placebo will be administered by self-injection under the skin at the study site or in an appropriate non-clinic setting (e.g., at home) by spring based prefilled auto injector/pen (AI/Pen). Participants must tolerate an injection of placebo with a prefilled auto injector/pen device to be used during the study prior to randomization. Participants will be randomly added to 1 of 4 groups using a 2:2:1:1 ratio: evolocumab 140 mg Q2W (86 participants total) evolocumab 420 mg QM (86 participants total) placebo Q2W (44 participants total) placebo QM (43 participants total). The dose frequencies of Q2W and QM will not be blinded but the identity of investigational product evolocumab or placebo will be blinded.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Evolocumab will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive evolocumab (AMG 145) every 2 weeks or monthly subcutaneously.
Placebo will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive placebo every 2 weeks or monthly subcutaneously.
Co-Primary Endpoint: Percent Change From Baseline in LDL-C: Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Co-Primary Endpoint: Percent Change From Baseline in LDL-C at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 12
Change From Baseline in LDL-C: Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C): Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
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Enrollment
259
Peking University Third Hospital
Beijing, Beijing Municipality, China
Beijing Hospital
Beijing, Beijing Municipality, China
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, China
Sun Yat-sen Memorial Hospital Sun Yat-sen University
Guangzhou, Guangdong, China
Guangzhou First Peoples  Hospital
Guangzhou, Guangdong, China
Guangzhou Red Cross Hospital
Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
The Second Nanning Peoples Hospital
Nanning, Guangxi, China
The First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, China
Wuhan Puai Hospital
Wuhan, Hubei, China
...and 21 more locations
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 12
Percent Change From Baseline in Apolipoprotein B (ApoB): Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in ApoB at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline and Week 12
Percent Change From Baseline in Total Cholesterol: Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Total Cholesterol at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline and Week 12
Percentage of Participants With Target LDL-C < 70 mg/dL (1.8 mmol/L): Mean of Weeks 10 and 12
Percentage of participants who were below the target LDL-C of 70 mg/dL (1.8 mmol/L) based on the mean LDL-C data collected at weeks 10 and 12.
Time frame: Weeks 10 and 12
Percentage of Participants With Target LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Time frame: Week 12
Percentage of Participants With LDL-C Response: Mean of Weeks 10 and 12
Percentage of participants who had LDL-C response (50% reduction of LDL-C from baseline) based on the mean LDL-C using the data collected at weeks 10 and 12.
Time frame: Baseline, Weeks 10 and 12
Percentage of Participants With LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 12
LDL-C Response is defined as a 50% reduction of LDL-C from Baseline.
Time frame: Baseline and Week 12
Percent Change From Baseline in Lipoprotein(a) [Lp(a)]: Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Lp(a) at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline and Week 12
Percent Change From Baseline in Triglycerides: Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline and Week 12
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C): Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline and Week 12
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C): Mean of Weeks 10 and 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in VLDL-C at Week 12
Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline and Week 12