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)
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT02107898
- 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 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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 216
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Q2W Placebo (for alirocumab) Placebo (for alirocumab) every two weeks (Q2W) added to stable lipid-modifying therapy (LMT). Placebo Q2W Lipid-Modifying Therapy (LMT) Placebo (for alirocumab) every two weeks (Q2W) added to stable lipid-modifying therapy (LMT). Alirocumab 75 mg/Up to 150 mg Q2W Lipid-Modifying Therapy (LMT) Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels above pre-specified threshold at Week 8 as defined in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012 i.e. * ≥100 mg/dL (2.59 mmol/L) in heFH participants or in non-familial hypercholesterolemia (non-FH) participants who had a history of documented coronary heart disease (CHD) * ≥120 mg/dL (3.10 mmol/L) in non-FH participants who had a history of documented diseases or other risk factors as categorized in primary prevention category III Alirocumab 75 mg/Up to 150 mg Q2W Alirocumab Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels above pre-specified threshold at Week 8 as defined in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012 i.e. * ≥100 mg/dL (2.59 mmol/L) in heFH participants or in non-familial hypercholesterolemia (non-FH) participants who had a history of documented coronary heart disease (CHD) * ≥120 mg/dL (3.10 mmol/L) in non-FH participants who had a history of documented diseases or other risk factors as categorized in primary prevention category III
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) From Baseline to Week 24 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).
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C 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 available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis From baseline to Week 24 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.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis From Baseline to Week 24 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).
Percent Change From Baseline in Apo 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 available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
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 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-HDL-C at Week 24 - On-Treatment Analysis From Baseline to Week 24 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).
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 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-HDL-C at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - ITT Analysis Up to Week 24 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.Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - On-Treatment Analysis Up to Week 24 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).
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis From Baseline to Week 24 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.
Trial Locations
- Locations (32)
Investigational Site Number 392016
🇯🇵Adachi-Ku, Japan
Investigational Site Number 392012
🇯🇵Chuo-Ku, Japan
Investigational Site Number 392024
🇯🇵Aki-Gun, Japan
Investigational Site Number 392028
🇯🇵Kaga-Shi, Japan
Investigational Site Number 392005
🇯🇵Kanazawa-Shi, Japan
Investigational Site Number 392029
🇯🇵Adachi-Ku, Japan
Investigational Site Number 392032
🇯🇵Fukui-Shi, Japan
Investigational Site Number 392013
🇯🇵Chuo-Ku, Japan
Investigational Site Number 392004
🇯🇵Hakusan-Shi, Japan
Investigational Site Number 392002
🇯🇵Kanazawa-Shi, Japan
Investigational Site Number 392011
🇯🇵Kuki-Shi, Japan
Investigational Site Number 392007
🇯🇵Mito-Shi, Japan
Investigational Site Number 392026
🇯🇵Kitakyushu-Shi, Japan
Investigational Site Number 392009
🇯🇵Kisarazu-Shi, Japan
Investigational Site Number 392023
🇯🇵Kawanishi-Shi, Japan
Investigational Site Number 392003
🇯🇵Komatsu-Shi, Japan
Investigational Site Number 392017
🇯🇵Matsumoto-Shi, Japan
Investigational Site Number 392014
🇯🇵Oota-Ku, Japan
Investigational Site Number 392019
🇯🇵Osaka-Shi, Japan
Investigational Site Number 392020
🇯🇵Osaka-Shi, Japan
Investigational Site Number 392022
🇯🇵Osaka-Shi, Japan
Investigational Site Number 392006
🇯🇵Moriya-Shi, Japan
Investigational Site Number 392018
🇯🇵Nagoya-Shi, Japan
Investigational Site Number 392030
🇯🇵Osaka-Shi, Japan
Investigational Site Number 392027
🇯🇵Oyabe-Shi, Japan
Investigational Site Number 392010
🇯🇵Saitama-Shi, Japan
Investigational Site Number 392015
🇯🇵Shinjuku-Ku, Japan
Investigational Site Number 392008
🇯🇵Tsuchiura-Shi, Japan
Investigational Site Number 392025
🇯🇵Takamatsu-Shi, Japan
Investigational Site Number 392031
🇯🇵Shizuoka-Shi, Japan
Investigational Site Number 392021
🇯🇵Suita-Shi, Japan
Investigational Site Number 392001
🇯🇵Yamagata-Shi, Japan