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

Acute Coronary Syndrome Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02984982
• Other study ID #: ALIROL08069
• Secondary ID: U1111-1184-8764
• Status: Completed
• Phase: Phase 4
• Start date: November 15, 2016
• Est. completion date: July 27, 2018

Study information

• Verified date: July 2019
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The duration of study per participant was 9 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: July 27, 2018
• Est. primary completion date: July 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Coronary Artery Disease
• Hypercholesterolemia
• Myocardial Ischemia
• Plaque, Atherosclerotic
• Syndrome

Intervention

Drug:
• Alirocumab SAR236553
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
• Atorvastatin
Pharmaceutical form: tablet Route of administration: oral
• Rosuvastatin
Pharmaceutical form: tablet Route of administration: oral
• Fenofibrate
Pharmaceutical form: tablet Route of administration: oral
• Bezafibrate
Pharmaceutical form: tablet Route of administration: oral
• Ezetimibe
Pharmaceutical form: tablet Route of administration: oral
• Antiplatelets
Pharmaceutical form: tablet or capsule Route of administration: oral
• Anticoagulants
Pharmaceutical form: tablet or capsule Route of administration: oral

Locations

Country	Name	City	State
Japan	Investigational Site Number 392026	Bunkyo-Ku
Japan	Investigational Site Number 392022	Chiyoda-ku
Japan	Investigational Site Number 392032	Fujisawa-shi
Japan	Investigational Site Number 392004	Fukui-shi
Japan	Investigational Site Number 392007	Fukuoka-shi
Japan	Investigational Site Number 392048	Fukuoka-shi
Japan	Investigational Site Number 392008	Gifu-shi
Japan	Investigational Site Number 392039	Hiroshima-shi
Japan	Investigational Site Number 392028	Isehara-shi
Japan	Investigational Site Number 392036	Itabashi-ku
Japan	Investigational Site Number 392037	Itabashi-ku
Japan	Investigational Site Number 392024	Izumisano-shi
Japan	Investigational Site Number 392013	Izunokuni-shi
Japan	Investigational Site Number 392020	Kawaguchi-shi
Japan	Investigational Site Number 392009	Kitakyushu-shi
Japan	Investigational Site Number 392034	Kitakyushu-shi
Japan	Investigational Site Number 392044	Kochi-shi
Japan	Investigational Site Number 392002	Kumamoto-shi
Japan	Investigational Site Number 392011	Kumamoto-shi
Japan	Investigational Site Number 392003	Kurashiki-shi
Japan	Investigational Site Number 392018	Matsuyama-shi
Japan	Investigational Site Number 392021	Morioka-shi
Japan	Investigational Site Number 392017	Nagakute-shi
Japan	Investigational Site Number 392047	Nagaoka-shi
Japan	Investigational Site Number 392033	Okayama-shi
Japan	Investigational Site Number 392006	Osaka-shi
Japan	Investigational Site Number 392010	Osaka-shi
Japan	Investigational Site Number 392045	Osaka-shi
Japan	Investigational Site Number 392046	Osaka-shi
Japan	Investigational Site Number 392015	Sagamihara-shi
Japan	Investigational Site Number 392019	Sakai-shi
Japan	Investigational Site Number 392035	Sapporo-shi
Japan	Investigational Site Number 392001	Tenri-shi
Japan	Investigational Site Number 392016	Toyoake-shi
Japan	Investigational Site Number 392025	Tsukuba-shi
Japan	Investigational Site Number 392040	Tsukuba-shi
Japan	Investigational Site Number 392005	Wakayama-shi
Japan	Investigational Site Number 392027	Yokohama-shi
Japan	Investigational Site Number 392043	Yokohama-shi

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	Absolute Change From Baseline in Normalized Total Atheroma Volume 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 normalized TAV as continuous fixed covariate.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	Absolute 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 effects, and the baseline lumen volume value as continuous fixed covariate.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 12, Week 36
Secondary	Percent 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.	Baseline, Week 12, Week 36
Secondary	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.	Baseline, Week 36
Secondary	Percent Change From Baseline in Apolipoprotein 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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	Percent Change From Baseline in Non-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 calculated non-HDL-C value and baseline calculated non-HDL-C value-by-time point interaction as continuous fixed covariates.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	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.	Baseline, Week 36
Secondary	Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) 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 A-1 value as continuous fixed covariate.	Baseline, Week 36
Secondary	Percent Change From Baseline in Apolipoprotein A-1 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 A-1 value as continuous fixed covariate.	Baseline, Week 36
Secondary	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.	Up to 36 weeks