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OpenTrials
Completed

NCT Number: NCT01507831

Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term)

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 long-term safety and tolerability of alirocumab in high cardiovascular risk participants with hypercholesterolemia not adequately controlled with their current lipid modifying therapy (LMT).

Secondary Objectives:

* To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo. * 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.

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Key information

Conditions

Hypercholesterolemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Investigational Site Number 032006, Buenos Aires, Argentina

Loading trial locations.

About this study

The maximum study duration was to be 89 weeks per participant, including a 3-week screening period, a 78-week randomized treatment period and 8-week follow-up period.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Either A or B below and who were not adequately controlled with their lipid-modifying therapy:

A) Participants with heterozygous familial hypercholesterolemia (heFH) with or without established coronary heart disease (CHD) or CHD risk equivalents

OR

B) Participants with hypercholesterolemia together with established CHD or CHD risk equivalents.

Exclusion criteria

  • Age < 18 years
  • LDL-C <70 mg/dL (< 1.81 mmol/L)
  • Fasting serum triglycerides > 400 mg/dL (>4.52 mmol/L)

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Treatment and study plan

Placebo (for alirocumab)

Drug

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a pre-filled syringe.

Alirocumab

Drug

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a pre-filled syringe.

Other names: SAR236553, REGN727, Praluent

Lipid-Modifying Therapy (LMT)

Drug

Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.

Primary outcomes

  1. Percentage of Participants Who Experienced Adverse Events (AEs)

    Time frame: Up to 10 weeks after last study drug administration (maximum of 86 weeks)

    Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

Secondary outcomes

  1. Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis

    Time frame: 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).

  2. Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

    Time frame: From Baseline to Week 52

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

  3. Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

    Time frame: From Baseline to Week 52

    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

  4. Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis

    Time frame: 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).

  5. Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 52

    Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

  6. Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis

    Time frame: 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.

  7. Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis

    Time frame: From Baseline to Week 52

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

  8. Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis

    Time frame: 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.

  9. Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis

    Time frame: 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).

  10. Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

    Time frame: 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.

  11. Percent Change From Baseline in Apo B at Week 12 - ITT Analysis

    Time frame: 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.

  12. Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis

    Time frame: 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.

  13. Percent Change From Baseline in Total-C at Week 12 - ITT Analysis

    Time frame: 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.

  14. Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis

    Time frame: Up to Week 52

    Very high CV risk: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents or non- Familial Hypercholesterolemia (FH). High CV risk: 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 family history of premature CHD). 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 52 regardless of status on- or off-treatment were included in imputation model.

  15. Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis

    Time frame: Up to Week 52

    Adjusted percentages at Week 24 were from 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).

  16. Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis

    Time frame: Up to Week 52

    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 52 regardless of status on- or off-treatment were included in the imputation model.

  17. Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis

    Time frame: Up to Week 52

    Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

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

    Time frame: From Baseline to Week 52

    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 from Week 4 to Week 52 regardless of status on-or off-treatment were included in the imputation model.

  19. Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis

    Time frame: 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.

  20. Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

    Time frame: 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.

  21. Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis

    Time frame: 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.

  22. Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis

    Time frame: 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.

  23. Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis

    Time frame: 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.

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

    Time frame: 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.

  25. Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis

    Time frame: 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.

Other outcomes

  1. Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis

    Time frame: 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.

  2. Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis

    Time frame: From Baseline to Week 52

    Adjusted LS means and standard errors at Week 52 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).

  3. Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis

    Time frame: From Baseline to Week 78

    Adjusted LS means and standard errors at Week 78 from MMRM model including all available post-baseline data from Week 4 to Week 78 regardless of status on- or off-treatment.

  4. Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis

    Time frame: From Baseline to Week 78

    Adjusted LS means and standard errors at Week 78 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 78 (i.e. up to 21 days after last injection).

  5. Percentage of Participants Who Experienced Cardiovascular (CV) Events

    Time frame: Up to 10 weeks after last study drug administration (maximum of 86 weeks)

    CV events included coronary heart disease (CHD) death; non-fatal myocardial infarction (MI); fatal and non-fatal ischemic stroke; unstable angina requiring hospitalization; congestive heart failure (CHF) requiring hospitalization; ischemia-driven coronary revascularization procedure. Reported events are CV events as confirmed by an independent Clinical Events Committee (CEC) that occurred during the treatment emergent period ( i.e. from first dose up to the last dose of study drug + 70 days).

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

Long-term Safety and Tolerability of SAR236553 (REGN727) in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid Modifying Therapy: A Randomized, Double-Blind, Placebo-Controlled Study

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Jan 11, 2012
Registry last updated
Dec 22, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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