Evaluation of Effect of Alirocumab on Coronary Atheroma V... | NCT02984982

ID	Type	Description	Link
U1111-1184-8764	Other Identifier	UTN

Status Module

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Standard of Care	Active Comparator	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 Drug: Rosuvastatin Drug: Fenofibrate Drug: Bezafibrate Drug: Ezetimibe Drug: Antiplatelets Drug: Anticoagulants
Alirocumab	Experimental	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 Drug: Atorvastatin Drug: Rosuvastatin Drug: Fenofibrate Drug: Bezafibrate Drug: Ezetimibe Drug: Antiplatelets Drug: Anticoagulants

Name	Type	Description	Arm Group Labels	Other Names
Alirocumab SAR236553	Drug	Pharmaceutical form: Solution for injection Route of administration: Subcutaneous	Alirocumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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

Eligibility Module

Eligibility 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.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 392026		Bunkyō City			Japan
Investigational Site Number 392022

PubMed Identifier	Type	Citation	Retractions
31434809	Derived	Ako J, Hibi K, Tsujita K, Hiro T, Morino Y, Kozuma K, Shinke T, Otake H, Uno K, Louie MJ, Takagi Y, Miyauchi K. Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients With Acute Coronary Syndrome - The ODYSSEY J-IVUS Trial. Circ J. 2019 Sep 25;83(10):2025-2033. doi: 10.1253/circj.CJ-19-0412. Epub 2019 Aug 20.
29606415

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin greater than or equal to [>=] 10 milligram per day [mg/day] or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-proprotein convertase subtilisin kexin type 9 (non-PCSK9) inhibitor lipid modifying therapies (LMTs) could be added by the investigators, if low-density lipoprotein cholesterol (LDL-C) target level less than (<) 100 milligrams per deciliter (mg/dL) could not be achieved.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 21, 2017	Jul 25, 2019

Arm/Group Information

ID	Title	Description
BG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
BG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-3.14± 0.97 OG001-4.79± 0.95

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis was performed using ANCOVA model which included fixed categorical effects of treatment arm and randomization strata, as well as the continuous fixed covariate of baseline normalized TAV.	ANCOVA		0.2279	Threshold for significance at 0.05 level.	LS mean difference	-1.64	Standard Error of the Mean	1.36	2-Sided	95	-4.32	1.04			Standard of Care vs Alirocumab		Superiority

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.

mITT population.

Posted

Least Squares Mean

Standard Error

percent atheroma volume

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Secondary

Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36

mITT population.

Posted

Least Squares Mean

Standard Error

cubic millimeter (mm^3)

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

mITT population.

Posted

Mean

Standard Error

mm^3

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

mITT population.

Posted

Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 milligram per day [mg/day] or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor lipid modifying therapies (LMTs) could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Secondary

Absolute Change From Baseline in Lumen Volume at Week 36

mITT population.

Posted

Mean

Standard Error

mm^3

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

mITT population.

Posted

Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline calculated LDL-C values.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 12, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Secondary

Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36

mITT population with one baseline and at least one post-baseline calculated LDL-C values.

Posted

Least Squares Mean

Standard Error

percent change

Baseline, Week 12, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and one post-baseline Apo B values.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Secondary

Percent Change From Baseline in Apolipoprotein B at Week 36

Participants of the mITT population with one baseline and one post-baseline Apo B values.

Posted

Least Squares Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C values.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Secondary

Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36

Participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C values.

Posted

Least Squares Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline TC values.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline TC values.

Posted

Least Squares Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and post-baseline Lp(a) values.

Posted

Mean

Standard Error

mg/dL

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and one post-baseline Lp(a) values.

Posted

Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline HDL-C values.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline HDL-C values.

Posted

Least Squares Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline fasting TGs values.

Posted

Mean

Standard Error

mg/dL

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Participants of the mITT population with one baseline and at least one post-baseline fasting TGs values.

Posted

Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Secondary

Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36

Participants of the mITT population with one baseline and one post-baseline Apo A-1 values.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Secondary

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

Participants of the mITT population with one baseline and one post-baseline Apo A-1 values.

Posted

Least Squares Mean

Standard Error

percent change

Baseline, Week 36

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

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.

Safety population: all participants who actually received at least 1 dose or part of a dose of the study drug, and analyzed according to the treatment actually received.

Posted

Count of Participants

Participants

Up to 36 weeks

ID	Title	Description
OG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.
OG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Standard of Care	During the study period, participants randomized to the SoC arm, in a non-blinded manner, received orally, stable dose of statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) with optional dose adjustment (within the range approved by health authority). In participants receiving statin monotherapy, non-statin, non-PCSK9 inhibitor LMTs could be added by the investigators, if LDL-C target level <100 mg/dL could not be achieved.	1	102	17	102	15	102
EG001	Alirocumab	Alirocumab (Praluent®) 75 mg SC injection Q2W on top of stable dose statin therapy (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day). Statin (atorvastatin >=10 mg/day or rosuvastatin >=5 mg/day) and non-statin LMTs were continued at the same doses after ACS diagnosis unless modifications were necessary. Alirocumab (Praluent®) dose was increased to 150 mg Q2W at Week 14, if the Week 12 LDL-C was >=100 mg/dL.	0	103	19	103	33	103

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anal abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Gastroenteritis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected102 at risk EG0011 affected103 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Lung adenocarcinoma stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Cerebral infarction	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0012 affected103 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0011 affected103 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected102 at risk EG0012 affected103 at risk
Angina unstable	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Cardiac failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Coronary artery dissection	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0013 affected103 at risk
Myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected102 at risk EG0011 affected103 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected102 at risk EG0011 affected103 at risk
Prinzmetal angina	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk
Incarcerated inguinal hernia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Liver disorder	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Nephropathy toxic	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Vascular stent stenosis	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Coronary artery reocclusion	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0011 affected103 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected102 at risk EG0010 affected103 at risk

Ancestor Terms

ID	Term
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006538	Heptanoic Acids
D005227	Fatty Acids
D008055	Lipids
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D005464	Fluorobenzenes
D006845	Hydrocarbons, Fluorinated
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D013450	Sulfones
D013457	Sulfur Compounds
D011743	Pyrimidines
D058607	Fibric Acids
D058610	Isobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D010647	Phenyl Ethers
D004987	Ethers
D001577	Benzophenones
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D010636	Phenols
D007659	Ketones
D001549	Benzamides
D001565	Benzoates
D000146	Acids, Carbocyclic
D002723	Chlorobenzoates
D001384	Azetidines
D001385	Azetines
D006401	Hematologic Agents
D045506	Therapeutic Uses
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses

ID	Term
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D014652	Vascular Diseases

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00015 affected102 at risk EG00127 affected103 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0016 affected103 at risk
Injection site reaction	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected102 at risk EG0017 affected103 at risk

ID	Term
C571059	alirocumab
D000069059	Atorvastatin
D000068718	Rosuvastatin Calcium
D011345	Fenofibrate
D001629	Bezafibrate
D000069438	Ezetimibe
D000925	Anticoagulants