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OpenTrials
Completed

NCT Number: NCT02107898

Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable daily statin therapy with or without other lipid modifying therapy in comparison with placebo after 24 weeks of treatment in heterozygous familial hypercholesterolemia (HeFH) or high cardiovascular risk participants with hypercholesterolemia.

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. * To evaluate the long-term effect of alirocumab in comparison with placebo on LDL-C after 52 weeks of treatment. * To evaluate the safety and tolerability of alirocumab. * To evaluate the development of anti-alirocumab antibodies. * To evaluate the pharmacokinetics of alirocumab.

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Key information

Conditions

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

Age range

20 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Investigational Site Number 392016, Adachi-Ku, Japan

Loading trial locations.

About this study

Total duration per participant of approximately 63 weeks (14 months) (screening: 3 weeks, double-blind treatment period: 52 weeks, and follow-up period: 8 weeks).

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 or non-familial hypercholesterolemia who were not adequately controlled with a stable daily dose of statin with or without other lipid modifying therapy, at stable dose prior to the screening visit (Week -3).

Exclusion criteria

  • LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit in participants with heterozygous familial hypercholesterolemia or in participants with non-familial hypercholesterolemia who had a history of documented coronary heart disease as described in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
  • LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit in participants with non-familial hypercholesterolemia who had a history of documented diseases or other risk factors as categorized in primary prevention category III as described in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
  • Not on a stable daily dose of lipid modifying therapy (including statin) within 4 weeks prior to the screening visit or between screening and randomization visits.
  • Age <20 years at the screening visit.

The above information is not intended to contain all considerations relevant to a participants' 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 an auto-injector.

Alirocumab

Drug

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Other names: SAR236553, REGN727, Praluent

Lipid-Modifying Therapy (LMT)

Drug

Statin (pravastatin, simvastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin) 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 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 outcomes

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

    Time frame: 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 from Week 4 to Week 24 (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 24

    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 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 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).

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

    Time frame: From baseline to Week 24

    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 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 24

    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 24 (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 24

    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 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 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).

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

    Time frame: From Baseline to Week 24

    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 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 24

    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 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 24

    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 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 24

    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  12. Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - ITT Analysis

    Time frame: Up to Week 24

    Calculated LDL-C goal was defined as:

    • <100 mg/dL (2.59 mmol/L) for heFH or non-FH participants who had a history of documented congestive heart disease (CHD), or
    • <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases (ischemic stroke, peripheral artery disease, chronic kidney disease or diabetes) or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

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

  13. Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - On-Treatment Analysis

    Time frame: Up to Week 24

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

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

    Time frame: From Baseline to Week 24

    Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression 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 in the imputation model.

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

    Time frame: From Baseline to Week 24

    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 24 regardless of status on-or off-treatment.

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

    Time frame: From Baseline to Week 24

    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

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

    Time frame: From Baseline to Week 24

    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

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

    Time frame: From Baseline to Week 24

    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 24 regardless of status on-or off-treatment.

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

    Time frame: From Baseline to Week 24

    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 24 regardless of status on-or off-treatment.

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

    Time frame: From Baseline to Week 24

    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

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

    Time frame: From Baseline to Week 24

    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 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 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 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).

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Alirocumab in Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid Modifying Therapy

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Apr 8, 2014
Registry last updated
Oct 4, 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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