Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II)
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT02023879
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by a regimen of Alirocumab including a starting dose of 150 mg every 4 weeks (Q4W) as add-on to non-statin lipid modifying background therapy or as monotherapy in comparison with placebo in participants with primary hypercholesterolemia not treated with a statin.
Secondary Objective:
* To evaluate the effects on other lipid parameters of Alirocumab 150 mg Q4W versus placebo.
* To evaluate the safety and tolerability of Alirocumab 150 mg Q4W.
Alirocumab 75 mg Q2W was added as a calibrator arm.
- Detailed Description
The core study duration was approximately 35 weeks per participant (screening: 3 weeks, double-blind treatment period: 24 weeks; follow-up: 8 weeks). Participants who successfully completed the treatment period had the possibility to participate in an optional open-label treatment period with Alirocumab 150 mg Q4W until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 233
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) Diet Alone Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. Alirocumab 150 mg Q4W/Up to 150 mg Q2W Placebo (for Alirocumab) Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. Placebo Q2W Placebo (for Alirocumab) Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. Alirocumab 150 mg Q4W/Up to 150 mg Q2W Diet Alone Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. Placebo Q2W Non-statin LMT Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. Placebo Q2W Diet Alone Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) Non-statin LMT Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. Alirocumab 150 mg Q4W/Up to 150 mg Q2W Non-statin LMT Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. Placebo Q2W Alirocumab Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) Alirocumab Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. Alirocumab 150 mg Q4W/Up to 150 mg Q2W Alirocumab Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.
- 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 Apo B 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 Non-HDL-C at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM 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 to Averaged Weeks 9 to 12 - ITT- Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
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 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 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM 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 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 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 - 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 Calculated LDL-C at Averaged Week 9 to 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) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
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 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 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 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 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) (on-treatment analysis).
Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis From Baseline to Week 24 Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and \<5%.
High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia.
Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion \>50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage.
Adjusted percentages at Week 24 were obtained from a 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.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 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 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 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-C at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis From Baseline to Week 24 Adjusted percentages at Week 24 from multiple imputation approach 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 A-1 at Week 24 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Percentage of Participants Achieving 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 from LOCF approach 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 12 - ITT Analysis From Baseline to Week 24 Adjusted means and standard errors at Week 12 from a 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 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 a 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 Apo A-1 at Week 12 - ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Percentage of Participants Achieving 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 from last observation carried forward (LOCF) approach including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Trial Locations
- Locations (43)
Investigational Site Number 554701
🇳🇿Christchurch, New Zealand
Investigational Site Number 724707
🇪🇸Barcelona, Spain
Investigational Site Number 724705
🇪🇸Granada, Spain
Investigational Site Number 724701
🇪🇸Zaragoza, Spain
Investigational Site Number 724703
🇪🇸A Coruna, Spain
Investigational Site Number 724702
🇪🇸Córdoba, Spain
Investigational Site Number 724706
🇪🇸Santiago De Compostela, Spain
Investigational Site Number 724710
🇪🇸Barcelona, Spain
Investigational Site Number 554702
🇳🇿Auckland, New Zealand
Investigational Site Number 840703
🇺🇸Beverly Hills, California, United States
Investigational Site Number 840708
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 840705
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 840707
🇺🇸Durham, North Carolina, United States
Investigational Site Number 840702
🇺🇸Summerville, South Carolina, United States
Investigational Site Number 036703
🇦🇺Ashford, Australia
Investigational Site Number 036702
🇦🇺Perth, Australia
Investigational Site Number 036701
🇦🇺Woolloongabba, Australia
Investigational Site Number 056702
🇧🇪Antwerpen, Belgium
Investigational Site Number 124703
🇨🇦Chicoutimi, Canada
Investigational Site Number 056701
🇧🇪Leuven, Belgium
Investigational Site Number 124701
🇨🇦Quebec, Canada
Investigational Site Number 124704
🇨🇦Sherbrooke, Canada
Investigational Site Number 124706
🇨🇦Toronto, Canada
Investigational Site Number 124705
🇨🇦Victoria, Canada
Investigational Site Number 124702
🇨🇦Vancouver, Canada
Investigational Site Number 208703
🇩🇰Aarhus, Denmark
Investigational Site Number 208702
🇩🇰Esbjerg, Denmark
Investigational Site Number 208701
🇩🇰Glostrup, Denmark
Investigational Site Number 208705
🇩🇰Køge, Denmark
Investigational Site Number 208704
🇩🇰Hvidovre, Denmark
Investigational Site Number 528701
🇳🇱Amsterdam, Netherlands
Investigational Site Number 528708
🇳🇱Den Helder, Netherlands
Investigational Site Number 528703
🇳🇱Hoorn, Netherlands
Investigational Site Number 724709
🇪🇸Sant Joan Despí, Spain
Investigational Site Number 840701
🇺🇸Sarasota, Florida, United States
Investigational Site Number 840706
🇺🇸Fall River, Massachusetts, United States
Investigational Site Number 528702
🇳🇱Hoogeveen, Netherlands
Investigational Site Number 528707
🇳🇱Venlo, Netherlands
Investigational Site Number 528709
🇳🇱Sneek, Netherlands
Investigational Site Number 056703
🇧🇪Haine-Saint-Paul, Belgium
Investigational Site Number 528704
🇳🇱Utrecht, Netherlands
Investigational Site Number 528706
🇳🇱Rotterdam, Netherlands
Investigational Site Number 840704
🇺🇸Atlantis, Florida, United States