Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)

Sanofi216 enrolled

Overview

Primary Objective: To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable daily statin therapy with or without other lipid modifying therapy in comparison with placebo after 24 weeks of treatment in heterozygous familial hypercholesterolemia (HeFH) or high cardiovascular risk participants with hypercholesterolemia. Secondary Objectives: * To evaluate the effect of alirocumab in comparison with placebo on LDL-C after 12 weeks of treatment. * To evaluate the effect of alirocumab on other lipid parameters. * To evaluate the long-term effect of alirocumab in comparison with placebo on LDL-C after 52 weeks of treatment. * To evaluate the safety and tolerability of alirocumab. * To evaluate the development of anti-alirocumab antibodies. * To evaluate the pharmacokinetics of alirocumab.

Total duration per participant of approximately 63 weeks (14 months) (screening: 3 weeks, double-blind treatment period: 52 weeks, and follow-up period: 8 weeks).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

216

Conditions

Hypercholesterolemia

Interventions

Eligibility

Sex: ALLMin age: 20 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion criteria: Participants with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia who were not adequately controlled with a stable daily dose of statin with or without other lipid modifying therapy, at stable dose prior to the screening visit (Week -3). Exclusion criteria: 1. LDL-C \<100 mg/dL (\<2.59 mmol/L) at the screening visit in participants with heterozygous familial hypercholesterolemia or in participants with non-familial hypercholesterolemia who had a history of documented coronary heart disease as described in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. 2. LDL-C \<120 mg/dL (\<3.10 mmol/L) at the screening visit in participants with non-familial hypercholesterolemia who had a history of documented diseases or other risk factors as categorized in primary prevention category III as described in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. 3. Not on a stable daily dose of lipid modifying therapy (including statin) within 4 weeks prior to the screening visit or between screening and randomization visits. 4. Age \<20 years at the screening visit. The above information is not intended to contain all considerations relevant to a participants' potential participation in a clinical trial.

Locations (32)

Investigational Site Number 392016

Adachi-Ku, Japan

Investigational Site Number 392029

Adachi-Ku, Japan

Investigational Site Number 392024

Aki-Gun, Japan

Investigational Site Number 392012

Chūōku, Japan

Investigational Site Number 392013

Chūōku, Japan

Investigational Site Number 392032

Fukui-shi, Japan

Investigational Site Number 392004

Hakusan-Shi, Japan

Investigational Site Number 392028

Kaga-Shi, Japan

Investigational Site Number 392002

Kanazawa, Japan

Investigational Site Number 392005

Kanazawa, Japan

...and 22 more locations

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 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 24

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 24 (i.e. up to 21 days after last injection) (on-treatment analysis).

Time frame: From Baseline to Week 24

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 available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

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 24 (i.e. up to 21 days after last injection).

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From baseline to Week 24

Percent Change From Baseline in Apo B 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 24 (i.e. up to 21 days after last injection).

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

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 24 (i.e. up to 21 days after last injection).

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - ITT Analysis

Calculated LDL-C goal was defined as: * \<100 mg/dL (2.59 mmol/L) for heFH or non-FH participants who had a history of documented congestive heart disease (CHD), or * \<120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases (ischemic stroke, peripheral artery disease, chronic kidney disease or diabetes) or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. 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 24 regardless of status on- or off-treatment were included in imputation model.

Time frame: Up to Week 24

Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - On-Treatment Analysis

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

Time frame: Up to Week 24

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

Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model 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.

Time frame: From Baseline to Week 24

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 by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Apo A1 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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

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 24 regardless of status on-or off-treatment.

Time frame: From Baseline to Week 24

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

Time frame: From Baseline to Week 24

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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Apo A1 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 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24