Back to results

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

Primary Purpose

Hypercholesterolemia, Acute Coronary Syndrome

Status

Completed

Phase

Phase 4

Locations

Japan

Study Type

Interventional

Intervention

Alirocumab SAR236553

Atorvastatin

Rosuvastatin

Fenofibrate

Bezafibrate

Ezetimibe

Antiplatelets

Anticoagulants

About this trial

This is an interventional treatment trial for Hypercholesterolemia

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care

Alirocumab

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at 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

Absolute Change From Baseline in Percent Atheroma Volume (PAV) at 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

Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at 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

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

Percent Change From Baseline in Lumen Volume at 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

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

Absolute Change From Baseline in Apolipoprotein B (Apo B) at 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

Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at 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

Absolute Change From Baseline in Total Cholesterol (TC) at 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

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

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

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

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

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

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

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

Percent Change From Baseline in Apolipoprotein A-1 at Week 36

Number of Participants With Cardiovascular (CV) Adverse Events

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.

Full Information

NCT ID

NCT02984982

First Posted

December 5, 2016

Last Updated

July 26, 2019

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02984982

Brief Title

Evaluation of Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia

Acronym

ODYSSEY J-IVUS

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

November 15, 2016 (Actual)

Primary Completion Date

July 27, 2018 (Actual)

Study Completion Date

July 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia, Acute Coronary Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

206 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Standard of Care

Arm Type

Active Comparator

Arm Description

Arm Title

Alirocumab

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Alirocumab SAR236553

Other Intervention Name(s)

Praluent

Intervention Description

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Intervention Type

Drug

Intervention Name(s)

Atorvastatin

Intervention Description