Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia

Phase 3

Completed

Conditions: Hypercholesterolemia

Interventions: Drug: Placebo for alirocumab
Drug: Alirocumab
Drug: placebo for ezetimibe
Drug: ezetimibe
Drug: atorvastatin
Drug: rosuvastatin
Drug: simvastatin

Registration Number: NCT02715726

Lead Sponsor: Sanofi

Brief Summary: Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy in comparison to ezetimibe 10 mg daily after 24 weeks of treatment in Asia in participants with hypercholesterolemia at high cardiovascular (CV) risk.

Secondary Objectives:

* To evaluate the effect of alirocumab 75 mg in comparison with ezetimibe 10 mg on LDL-C after 12 weeks of treatment.

* To evaluate the effect of alirocumab on other lipid parameters: e.g., apolipoprotein B (Apo B), non-high density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein a (Lp\[a\]), HDL-C, triglycerides (TG), apolipoprotein A-1 (Apo A-1).

* To evaluate the safety and tolerability of alirocumab.

* To evaluate the development of anti-alirocumab antibodies.

* To evaluate the pharmacokinetics (PK) of alirocumab.

Detailed Description: The maximum study duration was 35 weeks per participant, which included a screening period of up to 3 weeks, a 24-week randomized treatment period, and an 8-week post-treatment follow-up period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 615

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ezetimibe 10 mg	Placebo for alirocumab	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).
Ezetimibe 10 mg	atorvastatin	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).
Alirocumab 75 mg Q2W/up to 150 mg Q2W	placebo for ezetimibe	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8.
Alirocumab 75 mg Q2W/up to 150 mg Q2W	simvastatin	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8.
Ezetimibe 10 mg	ezetimibe	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).
Ezetimibe 10 mg	rosuvastatin	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).
Ezetimibe 10 mg	simvastatin	Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).
Alirocumab 75 mg Q2W/up to 150 mg Q2W	Alirocumab	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8.
Alirocumab 75 mg Q2W/up to 150 mg Q2W	atorvastatin	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8.
Alirocumab 75 mg Q2W/up to 150 mg Q2W	rosuvastatin	Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis	From Baseline to Week 24	Adjusted least square (LS) means and standard errors at Week 24 were obtained from mixed models analysis with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis	From Baseline to Week 12	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 up to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Analysis	From Baseline to Week 12	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis	From Baseline to Week 12	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis	From Baseline to Week 12	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: ITT Analysis	Up to Week 24	Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Percent Change From Baseline in Fasting Triglycerides at Week 12: ITT Analysis	From Baseline to Week 12	Adjusted means and standard errors at Week 12 were obtained by using multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis	From Baseline to Week 12	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis	From Baseline to Week 12	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis	From Baseline to Week 24	Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis	From Baseline to Week 24	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: On-Treatment Analysis	Up to Week 24	Adjusted percentages at Week 24 were obtained from multiple imputation approach including all available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis	From Baseline to Week 24	Adjusted means and standard errors at Week 24 were obtained by using multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis	From Baseline to Week 12	Adjusted means and standard errors at Week 12 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis	From Baseline to Week 12	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Trial Locations

Locations (62): Investigational Site Number 1560027
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Beijing, China
Investigational Site Number 1560043
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Beijing, China
Investigational Site Number 1560039
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Beijing, China
Investigational Site Number 1560012
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Beijing, China
Investigational Site Number 1560018
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Beijing, China
Investigational Site Number 1560006
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Changchun, China
Investigational Site Number 1560020
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Changchun, China
Investigational Site Number 1560023
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Changsha, China
Investigational Site Number 1560030
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Fuzhou, China
Investigational Site Number 1560005
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Guangzhou, China
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Investigational Site Number 1560027
🇨🇳Beijing, China