Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia (ODYSSEY J-IVUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02984982
Recruitment Status : Completed
First Posted : December 7, 2016
Results First Posted : September 9, 2019
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To compare the efficacy of alirocumab (Praluent®) with standard of care (SoC) on coronary atheroma progression (percent change in normalized total atheroma volume [TAV]) after 9 months of treatment in participants who had acute coronary syndrome (ACS) within 4 weeks prior to randomization, with hypercholesterolemia treated with statin.

Secondary Objectives:

  • To compare the efficacy of alirocumab (Praluent®) with SoC on secondary endpoints including absolute change in percent atheroma volume and normalized TAV after 9 months of treatment.
  • To evaluate the efficacy of alirocumab (Praluent®) on low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, triglycerides, non-high-density lipoprotein cholesterol and lipoprotein (a) after 9 months treatment.
  • To evaluate the safety of alirocumab (Praluent®) including the occurrence of cardiovascular events (coronary heart disease death, non-fatal myocardial infarction, fatal and non-fatal ischemic stroke, unstable angina requiring hospitalization) throughout the study.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Acute Coronary Syndrome Drug: Alirocumab SAR236553 Drug: Atorvastatin Drug: Rosuvastatin Drug: Fenofibrate Drug: Bezafibrate Drug: Ezetimibe Drug: Antiplatelets Drug: Anticoagulants Phase 4

Detailed Description:
The duration of study per participant was 9 months.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 206 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Blinded Intravascular Ultrasound Analysis, Parallel Group, Multicenter Study to Evaluate the Effect of Praluent® (Alirocumab) on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia Not Adequately Controlled With Statin
Actual Study Start Date : November 15, 2016
Actual Primary Completion Date : July 27, 2018
Actual Study Completion Date : July 27, 2018


Arm Intervention/treatment
Active Comparator: Standard of Care
Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level <100 milligrams per deciliter (mg/dL).
Drug: Atorvastatin

Pharmaceutical form: tablet

Route of administration: oral


Drug: Rosuvastatin

Pharmaceutical form: tablet

Route of administration: oral


Drug: Fenofibrate

Pharmaceutical form: tablet

Route of administration: oral


Drug: Bezafibrate

Pharmaceutical form: tablet

Route of administration: oral


Drug: Ezetimibe

Pharmaceutical form: tablet

Route of administration: oral


Drug: Antiplatelets

Pharmaceutical form: tablet or capsule

Route of administration: oral


Drug: Anticoagulants

Pharmaceutical form: tablet or capsule

Route of administration: oral


Experimental: Alirocumab
Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs.
Drug: Alirocumab SAR236553

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Other Name: Praluent

Drug: Atorvastatin

Pharmaceutical form: tablet

Route of administration: oral


Drug: Rosuvastatin

Pharmaceutical form: tablet

Route of administration: oral


Drug: Fenofibrate

Pharmaceutical form: tablet

Route of administration: oral


Drug: Bezafibrate

Pharmaceutical form: tablet

Route of administration: oral


Drug: Ezetimibe

Pharmaceutical form: tablet

Route of administration: oral


Drug: Antiplatelets

Pharmaceutical form: tablet or capsule

Route of administration: oral


Drug: Anticoagulants

Pharmaceutical form: tablet or capsule

Route of administration: oral





Primary Outcome Measures :
  1. Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36 [ Time Frame: Baseline, Week 36 ]
    Least-squares (LS) means and standard errors (SE) at Week 36 were obtained from analysis of covariance (ANCOVA) model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate.


Secondary Outcome Measures :
  1. Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36 [ Time Frame: Baseline, Week 36 ]
    LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and the baseline PAV as continuous fixed covariate.

  2. Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36 [ Time Frame: Baseline, Week 36 ]
    LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate.

  3. Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE at Week 36 were obtained from robust regression model with treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]), as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate.

  4. Percent Change From Baseline in External Elastic Membrane Volume at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and the baseline EEM volume value as continuous fixed covariate.

  5. Absolute Change From Baseline in Lumen Volume at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and the baseline lumen volume value as continuous fixed covariate.

  6. Percent Change From Baseline in Lumen Volume at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effect, and the baseline lumen volume value as continuous fixed covariate.

  7. Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 [ Time Frame: Baseline, Week 12, Week 36 ]
    Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates.

  8. Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 [ Time Frame: Baseline, Week 12, Week 36 ]
    Adjusted LS mean and SE at Week 12 and Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated LDL-C value and baseline calculated LDL-C value-by-time point interaction as continuous fixed covariates.

  9. Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate.

  10. Percent Change From Baseline in Apolipoprotein B at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and baseline Apo B value as continuous fixed covariate.

  11. Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates.

  12. Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates.

  13. Absolute Change From Baseline in Total Cholesterol (TC) at Week 36 [ Time Frame: Baseline, Week 36 ]
    LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline calculated TC value and baseline calculated TC value-by-time point interaction as continuous fixed covariates.

  14. Percent Change From Baseline in Total Cholesterol at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline TC value and baseline TC value-by-time point interaction as continuous fixed covariates.

  15. Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate.

  16. Percent Change From Baseline in Lipoprotein (a) at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE at Week 36 were obtained from robust regression model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effect, and baseline Lp(a) value as continuous fixed covariate.

  17. Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates.

  18. Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from mixed-effect model including all available post-baseline data from Week 4 to Week 36. Model included treatment arm (SoC arm, alirocumab arm), randomization strata (statin at ACS onset [Yes / No]), time point, treatment-by-time point and randomization strata-by-time point interaction as fixed categorical effects, and baseline HDL-C value and baseline HDL-C value-by-time point interaction as continuous fixed covariates.

  19. Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE were obtained from multiple imputation approach followed by robust regression model including fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) and the continuous fixed covariate of baseline fasting TGs value.

  20. Percent Change From Baseline in Fasting Triglycerides at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted mean and SE were obtained by multiple imputation approach followed by robust regression model included fixed categorical effect of treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) and the continuous fixed covariate of baseline fasting TGs value.

  21. Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate.

  22. Percent Change From Baseline in Apolipoprotein A-1 at Week 36 [ Time Frame: Baseline, Week 36 ]
    Adjusted LS mean and SE at Week 36 were obtained from ANCOVA model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset [Yes / No]) as fixed categorical effects, and baseline Apo A-1 value as continuous fixed covariate.

  23. Number of Participants With Cardiovascular (CV) Adverse Events [ Time Frame: Up to 36 weeks ]
    The suspected or confirmed CV events that occurred from randomization until end of the study visit were collected and reported. The various CV events included CV death, myocardial infarction, ischemic stroke, unstable angina requiring hospitalization , congestive heart failure requiring hospitalization, congestive heart failure requiring hospitalization, ischemia-driven coronary revascularization procedure.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Participants hospitalized for ACS (Acute ST-segment elevation myocardial infarction [STEMI], Acute non-ST-segment elevation myocardial infarction [NSTEMI], and unstable angina.
  • LDL-C >=100 mg/dL at ACS diagnosis.
  • Participants who has stenosis with at least >50% stenosis angiographically within 1 week after the ACS onset, and has analyzable coronary intravascular Ultrasound image.
  • Participants aged >=20 years old at ACS diagnosis.
  • Negative Hepatitis B surface antigen, negative Hepatitis B core antibody, and negative Hepatitis C antibody. Or, negative Hepatitis B surface antigen, positive Hepatitis B core antibody, negative Hepatitis B deoxyribonucleic acid, and negative Hepatitis C antibody.
  • Written informed consent.

Exclusion criteria:

  • Participants who had previously treated with at least one dose of any anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody.
  • Uncontrolled hypertension (multiple reading with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) between ACS diagnosis and randomization visit.
  • Known history of hemorrhagic stroke.
  • Currently under treatment for cancer.
  • Participants on LDL apheresis.
  • Any clinically significant abnormality identified that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, participants with short life expectancy.
  • Considered by the Investigator or any sub-Investigator as inappropriate for this study for any reason, including:

    • Unable to meet specific protocol requirements, such as scheduled visits;
    • Investigator or any sub-Investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc;
    • Presence of any other conditions (eg, geographic, social, etc.) actual or anticipated, that the Investigator feels would restrict or limit the participant's participation for the duration of the study.
  • Laboratory findings measured within 4 weeks after the ACS diagnosis (positive serum or urine pregnancy test in females of childbearing potential).

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02984982


Locations
Show Show 39 study locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] November 21, 2017
Statistical Analysis Plan  [PDF] October 11, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02984982    
Other Study ID Numbers: ALIROL08069
U1111-1184-8764 ( Other Identifier: UTN )
First Posted: December 7, 2016    Key Record Dates
Results First Posted: September 9, 2019
Last Update Posted: September 9, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Not available for request.

Layout table for additional information
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Acute Coronary Syndrome
Coronary Artery Disease
Myocardial Ischemia
Hypercholesterolemia
Syndrome
Plaque, Atherosclerotic
Disease
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Pathological Conditions, Anatomical
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Atorvastatin
Rosuvastatin Calcium
Ezetimibe
Fenofibrate
Bezafibrate
Anticoagulants
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action