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

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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

Tracking Information
First Submitted Date  ICMJE December 5, 2016
First Posted Date  ICMJE December 7, 2016
Results First Submitted Date  ICMJE July 26, 2019
Results First Posted Date  ICMJE September 9, 2019
Last Update Posted Date September 9, 2019
Actual Study Start Date  ICMJE November 15, 2016
Actual Primary Completion Date July 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2016)
Percent change in normalized total atheroma volume (TAV) [ Time Frame: Baseline to Week 36 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2016)
  • Absolute change in PAV [ Time Frame: Baseline to Week 36 ]
  • Absolute change in normalized TAV [ Time Frame: Baseline to Week 36 ]
  • Absolute change in external elastic membrane (EEM) volume and lumen volume [ Time Frame: Baseline to Week 36 ]
  • Percent change in EEM volume and lumen volume [ Time Frame: Baseline to Week 36 ]
  • Absolute change in calculated LDL-C [ Time Frame: Baseline to Week 12, and at Week 36 ]
  • Percent change in calculated LDL-C [ Time Frame: Baseline to Week 12, and at Week 36 ]
  • Absolute change in other lipid parameters [ Time Frame: Baseline to Week 36 ]
  • Percent change in other lipid parameters [ Time Frame: Baseline to Week 36 ]
  • Cardiovascular adverse events (CHD death, non-fatal MI, fatal and non-fatal ischemic and/or haemorrhagic stroke, unstable angina requiring hospitalization, CHF requiring hospitalization, ischemia-driven coronary revascularization procedure) [ Time Frame: Up to Week 36 ]
  • Incidence of adverse events based on standard and systematic assessment including physical examinations, electrocardiograms (ECGs), vital signs and laboratory tests [ Time Frame: Up to Week 36 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia
Official Title  ICMJE 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
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.
Detailed Description The duration of study per participant was 9 months.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypercholesterolemia
  • Acute Coronary Syndrome
Intervention  ICMJE
  • 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

Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Atorvastatin
    • Drug: Rosuvastatin
    • Drug: Fenofibrate
    • Drug: Bezafibrate
    • Drug: Ezetimibe
    • Drug: Antiplatelets
    • Drug: Anticoagulants
  • 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.
    Interventions:
    • Drug: Alirocumab SAR236553
    • Drug: Atorvastatin
    • Drug: Rosuvastatin
    • Drug: Fenofibrate
    • Drug: Bezafibrate
    • Drug: Ezetimibe
    • Drug: Antiplatelets
    • Drug: Anticoagulants
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 26, 2019)
206
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2016)
200
Actual Study Completion Date  ICMJE July 27, 2018
Actual Primary Completion Date July 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02984982
Other Study ID Numbers  ICMJE ALIROL08069
U1111-1184-8764 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Not available for request.
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP