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

ID: NCT02715726
Status: Recruiting
Phase: Phase 3
Start Date: July 27, 2016
First Submitted: March 16, 2016
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi, Regeneron Pharmaceuticals
Location: China, India, Thailand
Conditions: Hypercholesterolemia
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Study Description

Brief Summary

Primary Objective:

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

Secondary Objectives:

- To evaluate the effect of alirocumab on other lipid parameters: eg, Apolipoprotein (Apo) B, non-HDL-C, total cholesterol (TC), lipoprotein a (Lp[a]), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and 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 will be 35 weeks per patient, including a screening period of up to 3 weeks, a 24-week randomized treatment period, and an 8-week follow-up period.
Condition or disease Intervention/treatment Phase

Hypercholesterolemia

Drug: alirocumab SAR236553 (REGN727)
Other Names
Drug: placebo for alirocumab
Other Names
Drug: ezetimibe
Other Names
Drug: placebo for ezetimibe
Other Names
Drug: atorvastatin
Other Names
Drug: rosuvastatin
Other Names
Drug: simvastatin
Other Names
Phase 3

Tracking Information

First Submitted DateMarch 16, 2016
Last Update Posted DateFebruary 22, 2018
Start DateJuly 27, 2016
Anticipated Completion DateAugust 10, 2018
Primary Completion DateAugust 10, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Percent change in calculated LDL-C in the intent-to-treat (ITT) population [Time Frame: Baseline to Week 24]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Percent change in calculated LDL-C in the modified ITT (mITT) population [Time Frame: Baseline to Week 24]

  • Percent change in calculated LDL-C [Time Frame: Baseline to Week 12]

  • Percent change in Apo B [Time Frame: Baseline to Week 12 and Week 24]

  • Percent change in non-HDL-C [Time Frame: Baseline to Week 12 and Week 24]

  • Percent change in TC [Time Frame: Baseline to Week 12 and Week 24]

  • Proportion of patients reaching calculated LDL-C <70 mg/dL (1.81 mmol/L) [Time Frame: Week 24]

  • Percent change in Lp(a) [Time Frame: Baseline to Week 12 and Week 24]

  • Percent change in HDL-C [Time Frame: Baseline to Week 12 and Week 24]

  • Percent change in fasting TG [Time Frame: Baseline to Week 12 and Week 24]

  • Percent change in Apo A-1 [Time Frame: Baseline to Week 12 and Week 24]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEvaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia
Official TitleA Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Statin Therapy
Brief Summary

Primary Objective:

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

Secondary Objectives:

- To evaluate the effect of alirocumab on other lipid parameters: eg, Apolipoprotein (Apo) B, non-HDL-C, total cholesterol (TC), lipoprotein a (Lp[a]), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and 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 will be 35 weeks per patient, including a screening period of up to 3 weeks, a 24-week randomized treatment period, and an 8-week follow-up period.

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
600
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Hypercholesterolemia
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: alirocumab SAR236553 (REGN727)

Pharmaceutical form:solution Route of administration: subcutaneous

Other Names
Drug: placebo for alirocumab

Pharmaceutical form:solution Route of administration: subcutaneous

Other Names
Drug: ezetimibe

Pharmaceutical form:capsule Route of administration: oral

Other Names
Drug: placebo for ezetimibe

Pharmaceutical form:capsule Route of administration: oral

Other Names
Drug: atorvastatin

Pharmaceutical form:tablet Route of administration: oral

Other Names
Drug: rosuvastatin

Pharmaceutical form:tablet Route of administration: oral

Other Names
Drug: simvastatin

Pharmaceutical form:tablet Route of administration: oral

Other Names
Study Groups/Cohorts
Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial

Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial

Study Arms
Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : alirocumab SAR236553 (REGN727)
Pharmaceutical form:solution Route of administration: subcutaneous

Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : placebo for ezetimibe
Pharmaceutical form:capsule Route of administration: oral

Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : atorvastatin
Pharmaceutical form:tablet Route of administration: oral

Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : rosuvastatin
Pharmaceutical form:tablet Route of administration: oral

Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : simvastatin
Pharmaceutical form:tablet Route of administration: oral

Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : simvastatin
Pharmaceutical form:tablet Route of administration: oral

Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : rosuvastatin
Pharmaceutical form:tablet Route of administration: oral

Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : atorvastatin
Pharmaceutical form:tablet Route of administration: oral

Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : placebo for alirocumab
Pharmaceutical form:solution Route of administration: subcutaneous

Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : ezetimibe
Pharmaceutical form:capsule Route of administration: oral

Arm Intervention/Treatment
Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : alirocumab SAR236553 (REGN727)
Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : placebo for ezetimibe
Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : atorvastatin
Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : rosuvastatin
Experimental Alirocumab + Placebo
Alirocumab subcutaneous (SC) injection plus ezetimibe placebo administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : simvastatin
Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : simvastatin
Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : rosuvastatin
Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : atorvastatin
Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : placebo for alirocumab
Active Comparator Placebo + Ezetimibe
Alirocumab placebo injection through SC administration plus ezetimibe administered daily, orally. Background statin therapy (atorvastatin, rosuvastatin, or simvastatin) continued during the course of the trial
Drug : ezetimibe

Recruitment Information

Recruitment Status:Recruiting
Enrollment600
Completion DateAugust 10, 2018
Eligibility Criteria: Inclusion criteria:
Patients with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin at a stable dose for at least 4 weeks prior to the screening visit (Week -3).
Exclusion criteria:
- Patients without established CHD or CHD risk equivalents.
- LDL-C <70 mg/dL (<1.81 mmol/L) at the screening visit (Week -3) in patients with history of documented CV disease.
- LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week -3) in patients without history of documented CV disease.
- Change in statin dose or dose regimen from screening to randomization.
- Currently taking a statin other than atorvastatin, rosuvastatin, or simvastatin.
- Atorvastatin, rosuvastatin, or simvastatin is not taken daily or not taken at a registered dose.
- Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg.
- Use of cholesterol absorption inhibitor (ie, ezetimibe), omega-3 fatty acid (at doses ≥1000 mg daily), nicotinic acid, fibrates, bile acid-binding sequestrant, or red yeast rice products in the past 4 weeks prior to screening visit (Week -3).
- Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L) at the screening period.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
China
India
Thailand

Administrative Information

NCT Number:NCT02715726
Other Study ID Numbers
EFC13889
U1111-1150-8859
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
Investigators
Study Director
Clinical Sciences & Operations
Sanofi