Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)

Sanofi316 enrolled

Overview

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9). Primary Objective of the study: * To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular (CV) risk participants with hypercholesterolemia Secondary Objectives: * To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points * To evaluate the effect of alirocumab on other lipid parameters * To evaluate the safety and tolerability of alirocumab

The maximum study duration was 62 weeks per participant, including a 2-week screening period, 52-week randomized treatment period, and 8-week follow-up period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

316

Conditions

Hypercholesterolemia

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin with or without other LMT, both at stable dose for at least 4 weeks to 6 weeks prior to screening (Week -2) Exclusion criteria: * Age \<18 or legal age of adulthood, whichever was greater * Participants without established CHD or CHD risk equivalent * LDL-C \<70 mg/dL (\<1.81 mmol/L) and participants with a history of documented cardiovascular disease * LDL-C \<100 mg/dL (\<2.59 mmol/L) and participants without a history of documented cardiovascular disease * Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit (Week -2) and from screening to randomization * Fasting serum triglycerides \> 400 mg/dL (\>4.52 mmol/L) The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (76)

Investigational Site Number 840857

Birmingham, Alabama, United States

Investigational Site Number 840891

Mobile, Alabama, United States

Investigational Site Number 840876

Montgomery, Alabama, United States

Investigational Site Number 840865

Glendale, Arizona, United States

Investigational Site Number 840826

Jonesboro, Arkansas, United States

Outcomes

Primary Outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis

Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 52

Secondary Outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection) (on-treatment analysis).

Time frame: From Baseline to Week 52

Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

Time frame: From Baseline to Week 52

Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From baseline to Week 52

Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

Time frame: From Baseline to Week 52

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

Time frame: From Baseline to Week 52

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Apo B at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Total-C at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis

Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis

Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.

Time frame: Up to Week 52

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis

Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.

Time frame: Up to Week 52

Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis

Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.

Time frame: From baseline to Week 52

Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

Adjusted means and standard errors at Week 24 from multiple imputation approach followed be robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Apolipoprotein A-1 at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52

Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 52