Evaluation of Alirocumab in Addition to Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia in South Korea and Taiwan
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT02289963
- 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 with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular risk participants with hypercholesterolemia in South Korea and Taiwan.
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: apolipoprotein B (Apo B), non high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein (a) (Lp \[a\]), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), and apolipoprotein A-1 (Apo A-1).
* To evaluate the safety and tolerability of alirocumab.
* To evaluate the development of anti-alirocumab antibodies (ADA).
- Detailed Description
The maximum study duration was approximately 35 weeks per participant, including up to 3 weeks screening period, 24 weeks double-blind treatment period, and 8 weeks follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 199
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) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. Placebo Q2W Lipid-Modifying Therapy (LMT) Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. Alirocumab 75 mg Q2W/Up to 150 mg Q2W Lipid-Modifying Therapy (LMT) Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
- 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 up 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 12 - On-Treatment Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
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 up 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 were obtained from MMRM model including all available post-baseline data up 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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis From Baseline to Week 24 Adjusted percentages at Week 24 were obtained from multiple imputation approach model including available post-baseline on-treatment data up 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 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data up to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Percent Change From Baseline in High Density Lipoprotein (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 up 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 up 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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
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 up to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).
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 up 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 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).
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 were obtained from MMRM model including all available post-baseline data up 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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data up to Week 24 regardless of status on- or off-treatment were included in the imputation model.
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 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
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 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up 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 were obtained from MMRM model including all available post-baseline data up 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 were obtained from multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Trial Locations
- Locations (27)
Investigational Site Number 410017
🇰🇷Busan, Korea, Republic of
Investigational Site Number 410018
🇰🇷Jeonju-Si, Korea, Republic of
Investigational Site Number 410009
🇰🇷Anyang-Si, Korea, Republic of
Investigational Site Number 410007
🇰🇷Busan, Korea, Republic of
Investigational Site Number 158002
🇨🇳Taipei, Taiwan
Investigational Site Number 410006
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410001
🇰🇷Anyang, Korea, Republic of
Investigational Site Number 410011
🇰🇷Goyang-Si, Korea, Republic of
Investigational Site Number 410002
🇰🇷Daegu, Korea, Republic of
Investigational Site Number 410003
🇰🇷Gwangju, Korea, Republic of
Investigational Site Number 410012
🇰🇷Incheon, Korea, Republic of
Investigational Site Number 410005
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410004
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410008
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410010
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410015
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410013
🇰🇷Ulsan, Korea, Republic of
Investigational Site Number 158007
🇨🇳Changhua, Taiwan
Investigational Site Number 158008
🇨🇳Tainan, Taiwan
Investigational Site Number 158010
🇨🇳Kaohsiung, Taiwan
Investigational Site Number 158011
🇨🇳Kaohsiung, Taiwan
Investigational Site Number 158006
🇨🇳Taichung, Taiwan
Investigational Site Number 158009
🇨🇳Tainan Hsien, Taiwan
Investigational Site Number 158001
🇨🇳Taipei, Taiwan
Investigational Site Number 158004
🇨🇳Taoyuan Hsien, Taiwan
Investigational Site Number 158005
🇨🇳Hsinchu, Taiwan
Investigational Site Number 158003
🇨🇳Taipei, Taiwan