Trial Outcomes & Findings for Evaluation of Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia (NCT NCT02984982)

Last Updated: 2019-09-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

206 participants

Primary outcome timeframe

Baseline, Week 36

Results posted on

2019-09-09

Participant Flow

The study was conducted at 39 active centers in Japan. Overall 214 participants were screened between 15 November 2016 and 02 November 2017, of whom 8 were screen failure and 206 were randomized to either alirocumab arm or standard of care (SoC) arm.

Randomization was stratified by 'on statin therapy' or 'not on statin therapy' at the time of acute coronary syndrome (ACS) onset.

Participant milestones

Participant milestones
Measure	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.	Alirocumab Alirocumab (Praluent®) 75 mg subcutaneous (SC) injection every 2 weeks (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.
Overall Study STARTED	102	104
Overall Study Treated	102	103
Overall Study COMPLETED	94	94
Overall Study NOT COMPLETED	8	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Alirocumab Alirocumab (Praluent®) 75 mg subcutaneous (SC) injection every 2 weeks (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.
Overall Study Adverse Event	2	5
Overall Study Poor Compliance to Protocol	4	4
Overall Study Withdrawal by Subject	2	0
Overall Study Randomized but not treated	0	1

Baseline Characteristics

"Number analyzed" = Number of participants evaluable for the specified baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care n=102 Participants 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.	Alirocumab n=104 Participants 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.	Total n=206 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 11.9 • n=102 Participants	61.7 years STANDARD_DEVIATION 10.9 • n=104 Participants	60.9 years STANDARD_DEVIATION 11.4 • n=206 Participants
Sex: Female, Male Female	19 Participants n=102 Participants	21 Participants n=104 Participants	40 Participants n=206 Participants
Sex: Female, Male Male	83 Participants n=102 Participants	83 Participants n=104 Participants	166 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=102 Participants	0 Participants n=104 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	102 Participants n=102 Participants	104 Participants n=104 Participants	206 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=102 Participants	0 Participants n=104 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=102 Participants	0 Participants n=104 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	0 Participants n=102 Participants	0 Participants n=104 Participants	0 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=102 Participants	0 Participants n=104 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=102 Participants	0 Participants n=104 Participants	0 Participants n=206 Participants
Calculated LDL-C in mg/dL	95.2 mg/dL STANDARD_DEVIATION 22.6 • n=98 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	98.5 mg/dL STANDARD_DEVIATION 22.9 • n=103 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.	96.9 mg/dL STANDARD_DEVIATION 22.8 • n=201 Participants • "Number analyzed" = Number of participants evaluable for the specified baseline measure.

PRIMARY outcome

Timeframe: Baseline, Week 36

Population: Modified intent-to-treat (mITT) population: all participants who were allocated to a randomized treatment, recorded in the registration center database, had at least one dose or part of dose of study drug and had 2 analyzable normalized TAV values, 1 assessed before randomization, and one assessed after 24 weeks of treatment.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36	-3.14 percent change Standard Error 0.97	-4.79 percent change Standard Error 0.95

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: mITT population.

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36	-1.28 percent atheroma volume Standard Error 0.39	-1.42 percent atheroma volume Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: mITT population.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36	-4.73 cubic millimeter (mm^3) Standard Error 1.02	-5.77 cubic millimeter (mm^3) Standard Error 1.00

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: mITT population.

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36	-8.23 mm^3 Standard Error 1.85	-10.01 mm^3 Standard Error 1.81

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: mITT population.

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in External Elastic Membrane Volume at Week 36	-0.86 percent change Standard Error 0.93	-3.18 percent change Standard Error 0.91

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: mITT population.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in Lumen Volume at Week 36	-1.25 mm^3 Standard Error 1.38	-0.93 mm^3 Standard Error 1.35

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: mITT population.

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in Lumen Volume at Week 36	1.20 percent change Standard Error 1.26	-0.86 percent change Standard Error 1.23

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=85 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 Week 12	-9.6 mg/dL Standard Error 1.7	-62.4 mg/dL Standard Error 1.6
Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 Week 36	-15.5 mg/dL Standard Error 1.8	-63.2 mg/dL Standard Error 1.8

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 36

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

Outcome measures

Outcome measures
Measure	Standard of Care n=85 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 Week 12	-7.57 percent change Standard Error 1.91	-64.53 percent change Standard Error 1.83
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36 Week 36	-13.40 percent change Standard Error 1.99	-63.94 percent change Standard Error 1.91

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=88 Participants 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.	Alirocumab n=92 Participants 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.
Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36	-16.8 mg/dL Standard Error 1.4	-51.0 mg/dL Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline, Week 36

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

Outcome measures

Outcome measures
Measure	Standard of Care n=88 Participants 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.	Alirocumab n=92 Participants 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.
Percent Change From Baseline in Apolipoprotein B at Week 36	-16.61 percent change Standard Error 1.56	-55.13 percent change Standard Error 1.53

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36	-20.3 mg/dL Standard Error 2.0	-69.2 mg/dL Standard Error 2.0

SECONDARY outcome

Timeframe: Baseline, Week 36

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

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36	-14.06 percent change Standard Error 1.71	-54.50 percent change Standard Error 1.67

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in Total Cholesterol (TC) at Week 36	-15.2 mg/dL Standard Error 2.3	-61.7 mg/dL Standard Error 2.2

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in Total Cholesterol at Week 36	-7.59 percent change Standard Error 1.35	-35.43 percent change Standard Error 1.32

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=88 Participants 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.	Alirocumab n=92 Participants 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.
Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36	-10.3 mg/dL Standard Error 0.5	-15.5 mg/dL Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=88 Participants 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.	Alirocumab n=92 Participants 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.
Percent Change From Baseline in Lipoprotein (a) at Week 36	-17.23 percent change Standard Error 2.60	-55.76 percent change Standard Error 2.54

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36	4.7 mg/dL Standard Error 0.9	8.1 mg/dL Standard Error 0.9

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36	12.19 percent change Standard Error 2.30	21.04 percent change Standard Error 2.25

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36	-26.2 mg/dL Standard Error 4.7	-35.3 mg/dL Standard Error 4.5

SECONDARY outcome

Timeframe: Baseline, Week 36

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

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=89 Participants 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.	Alirocumab n=93 Participants 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.
Percent Change From Baseline in Fasting Triglycerides at Week 36	-8.85 percent change Standard Error 3.62	-18.37 percent change Standard Error 3.51

SECONDARY outcome

Timeframe: Baseline, Week 36

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

Outcome measures

Outcome measures
Measure	Standard of Care n=88 Participants 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.	Alirocumab n=92 Participants 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.
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36	3.8 mg/dL Standard Error 1.9	12.0 mg/dL Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline, Week 36

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

Outcome measures

Outcome measures
Measure	Standard of Care n=88 Participants 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.	Alirocumab n=92 Participants 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.
Percent Change From Baseline in Apolipoprotein A-1 at Week 36	4.61 percent change Standard Error 1.62	11.75 percent change Standard Error 1.58

SECONDARY outcome

Timeframe: Up to 36 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=102 Participants 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.	Alirocumab n=103 Participants 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.
Number of Participants With Cardiovascular (CV) Adverse Events Unstable angina requiring hospitalization	0 Participants	0 Participants
Number of Participants With Cardiovascular (CV) Adverse Events Cardiovascular death	0 Participants	0 Participants
Number of Participants With Cardiovascular (CV) Adverse Events Myocardial infarction	3 Participants	2 Participants
Number of Participants With Cardiovascular (CV) Adverse Events Ischemic stroke	0 Participants	2 Participants
Number of Participants With Cardiovascular (CV) Adverse Events Congestive heart failure requiring hospitalization	0 Participants	0 Participants
Number of Participants With Cardiovascular (CV) Adverse Events Ischemia led coronary revascularization procedure	2 Participants	4 Participants

Adverse Events

Standard of Care

Serious events: 17 serious events

Other events: 15 other events

Deaths: 1 deaths

Alirocumab

Serious events: 19 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Standard of Care n=102 participants at risk 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.	Alirocumab n=103 participants at risk 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.
Infections and infestations Nasopharyngitis	14.7% 15/102 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 21 days after last dose of study drug, or end of study, whichever comes first (up to 39 weeks) regardless of seriousness or relationship to investigational product Reported AEs and deaths are treatment-emergent adverse events that developed/worsened during the treatment-emergent period (time from first dose of investigational medicinal product (IMP) up to last dose of IMP +21 days, or end of study, whichever comes first). Analysis was performed on safety population.	26.2% 27/103 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 21 days after last dose of study drug, or end of study, whichever comes first (up to 39 weeks) regardless of seriousness or relationship to investigational product Reported AEs and deaths are treatment-emergent adverse events that developed/worsened during the treatment-emergent period (time from first dose of investigational medicinal product (IMP) up to last dose of IMP +21 days, or end of study, whichever comes first). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/102 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 21 days after last dose of study drug, or end of study, whichever comes first (up to 39 weeks) regardless of seriousness or relationship to investigational product Reported AEs and deaths are treatment-emergent adverse events that developed/worsened during the treatment-emergent period (time from first dose of investigational medicinal product (IMP) up to last dose of IMP +21 days, or end of study, whichever comes first). Analysis was performed on safety population.	5.8% 6/103 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 21 days after last dose of study drug, or end of study, whichever comes first (up to 39 weeks) regardless of seriousness or relationship to investigational product Reported AEs and deaths are treatment-emergent adverse events that developed/worsened during the treatment-emergent period (time from first dose of investigational medicinal product (IMP) up to last dose of IMP +21 days, or end of study, whichever comes first). Analysis was performed on safety population.
General disorders Injection site reaction	0.00% 0/102 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 21 days after last dose of study drug, or end of study, whichever comes first (up to 39 weeks) regardless of seriousness or relationship to investigational product Reported AEs and deaths are treatment-emergent adverse events that developed/worsened during the treatment-emergent period (time from first dose of investigational medicinal product (IMP) up to last dose of IMP +21 days, or end of study, whichever comes first). Analysis was performed on safety population.	6.8% 7/103 • All Adverse Events (AEs) were collected from signature of the informed consent form up to 21 days after last dose of study drug, or end of study, whichever comes first (up to 39 weeks) regardless of seriousness or relationship to investigational product Reported AEs and deaths are treatment-emergent adverse events that developed/worsened during the treatment-emergent period (time from first dose of investigational medicinal product (IMP) up to last dose of IMP +21 days, or end of study, whichever comes first). Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
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