Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH)
- Conditions
- Hypercholesterolaemia
- Interventions
- Registration Number
- NCT01617655
- Lead Sponsor
- Sanofi
- Brief Summary
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).
Primary Objective of the study:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.
Secondary Objectives:
* To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
* To evaluate the effects of alirocumab on other lipid parameters
* To evaluate the safety and tolerability of alirocumab
- Detailed Description
The maximum study duration was planned to be 89 weeks per participant including participants who successfully completed the 78-week treatment period had the possibility to join an open-label extension study (LTS13463, NCT01954394) at the end of the treatment period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 107
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 two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks. Placebo Q2W Lipid Modifying Therapy (LMT) Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks. Alirocumab 150 mg Q2W Alirocumab Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks. Alirocumab 150 mg Q2W Lipid Modifying Therapy (LMT) Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis From Baseline to Week 52 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).
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis From Baseline to Week 52 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.
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - On-Treatment Analysis Up to Week 52 Adjusted percentages at Week 24 from a 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.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis From Baseline to Week 52 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 52 regardless of status on-or off-treatment.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis From Baseline to Week 52 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 (on-treatment analysis).
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis From Baseline to Week 52 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).
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis From Baseline to Week 52 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).
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis Up to Week 52 Very high CV risk participants: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents. High CV risk participants: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to \<60 ml/minute/1.73 m\^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of \>2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or a family history of premature CHD). 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 52 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 52 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 52 regardless of status on-or off-treatment.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis Up to Week 52 Adjusted percentages at Week 24 from multiple imputation approach including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis From Baseline to Week 52 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.
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis Up to Week 52 Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.
Trial Locations
- Locations (35)
Investigational Site Number 840742
🇺🇸Bell Gardens, California, United States
Investigational Site Number 840743
🇺🇸Northridge, California, United States
Investigational Site Number 840710
🇺🇸Ponte Vedra, Florida, United States
Investigational Site Number 840701
🇺🇸New York, New York, United States
Investigational Site Number 840702
🇺🇸Durham, North Carolina, United States
Investigational Site Number 528713
🇳🇱Amsterdam, Netherlands
Investigational Site Number 124703
🇨🇦Sherbrooke, Canada
Investigational Site Number 124704
🇨🇦Quebec, Canada
Investigational Site Number 643708
🇷🇺Moscow, Russian Federation
Investigational Site Number 643709
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 710704
🇿🇦Bloemfontein, South Africa
Investigational Site Number 710701
🇿🇦Bloemfontein, South Africa
Investigational Site Number 710706
🇿🇦Cap Town, South Africa
Investigational Site Number 710702
🇿🇦Parktown, South Africa
Investigational Site Number 710703
🇿🇦Somerset West, South Africa
Investigational Site Number 840703
🇺🇸Newport Beach, California, United States
Investigational Site Number 840705
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number 840736
🇺🇸Dallas, Texas, United States
Investigational Site Number 840712
🇺🇸Newport Beach, California, United States
Investigational Site Number 840738
🇺🇸Miami, Florida, United States
Investigational Site Number 840713
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number 840714
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840709
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number 840734
🇺🇸Washington, District of Columbia, United States
Investigational Site Number 528701
🇳🇱Amsterdam, Netherlands
Investigational Site Number 528704
🇳🇱Groningen, Netherlands
Investigational Site Number 528716
🇳🇱Leiden, Netherlands
Investigational Site Number 528709
🇳🇱Utrecht, Netherlands
Investigational Site Number 643706
🇷🇺Arkhangelsk, Russian Federation
Investigational Site Number 643705
🇷🇺Kazan, Russian Federation
Investigational Site Number 643703
🇷🇺Moscow, Russian Federation
Investigational Site Number 643711
🇷🇺Moscow, Russian Federation
Investigational Site Number 643702
🇷🇺Saint Petersburg, Russian Federation
Investigational Site Number 643710
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 643707
🇷🇺Yaroslavl, Russian Federation