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Completed

NCT Number: NCT01623115

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

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

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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 040403, Graz, Austria

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Participants with heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy

Exclusion criteria

  • Age < 18 years or legal age of adulthood, whichever is greater
  • LDL-C < 70 mg/dL (1.81 mmol/L) and with cardiovascular disease
  • LDL-C < 100 mg/dL (2.59 mmol/L) and without cardiovascular disease
  • Fasting serum triglycerides > 400 mg/dL (4.52 mmol/L)
  • Known history of homozygous familial hypercholesterolemia

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

Treatment and study plan

Alirocumab

Drug

Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).

Other names: SAR236553, REGN727, Praluent

Placebo (for alirocumab)

Drug

Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).

Lipid Modifying Therapy (LMT)

Drug

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

Primary 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).

Secondary outcomes

  1. 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 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).

  2. 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 including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

  3. 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).

  4. Percent Change From Baseline in Apolipoprotein B (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.

  5. 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 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).

  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

    Time frame: 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 multiple imputation approach 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.

  14. 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

    Time frame: 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.

  15. Percentage of Participants Achieving 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 from multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

  16. Percentage of Participants Achieving 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 on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.

  17. 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 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.

  18. 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.

  19. 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.

  20. Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) 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.

  21. 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.

  22. 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.

  23. 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.

  24. Percent Change From Baseline in Apo A-1 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 - 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).

  2. 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 including all available post-baseline data from Week 4 to Week 78 regardless of status on-or off-treatment.

  3. 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).

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

Acronym: ODYSSEY FH I

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Jun 19, 2012
Registry last updated
Feb 8, 2016

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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