Trial Outcomes & Findings for Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN) (NCT NCT02107898)

Results Overview

Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

216 participants

Primary outcome timeframe

From Baseline to Week 24

Results posted on

2016-10-04

Participant Flow

The study was conducted at 31 centers in Japan. A total of 319 participants were screened between March 2014 and July 2014, 103 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.

Randomization was stratified according to heterozygous familial hypercholesterolemia (heFH) population. Assignment to treatment arms was done using an Interactive Web Response System in 1:2 (Placebo: Alirocumab) ratio after confirmation of selection criteria. 216 participants were randomized.

Participant milestones

Participant milestones
Measure	Placebo Q2W Placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) added to stable lipid-modifying therapy (LMT) for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Study STARTED	72	144
Overall Study Treated	72	143
Overall Study COMPLETED	66	132
Overall Study NOT COMPLETED	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Q2W Placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) added to stable lipid-modifying therapy (LMT) for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Overall Study Adverse Event	4	7
Overall Study Poor compliance to protocol	0	1
Overall Study Participant moved	0	2
Overall Study Consent withdrawn by participant	2	1
Overall Study Randomized but not treated	0	1

Baseline Characteristics

Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=144 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.	Total n=216 Participants Total of all reporting groups
Age, Continuous	61.8 years STANDARD_DEVIATION 9.0 • n=5 Participants	60.3 years STANDARD_DEVIATION 9.7 • n=7 Participants	60.8 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	60 Participants n=7 Participants	85 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	84 Participants n=7 Participants	131 Participants n=5 Participants
Calculated LDL-C in mg/dL	141.6 mg/dL STANDARD_DEVIATION 26.7 • n=5 Participants	140.9 mg/dL STANDARD_DEVIATION 26.8 • n=7 Participants	141.2 mg/dL STANDARD_DEVIATION 26.7 • n=5 Participants
Calculated LDL-C in mmol/L	3.668 mmol/L STANDARD_DEVIATION 0.691 • n=5 Participants	3.650 mmol/L STANDARD_DEVIATION 0.693 • n=7 Participants	3.656 mmol/L STANDARD_DEVIATION 0.691 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.

Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)	1.6 percent change Standard Error 1.8	-62.5 percent change Standard Error 1.3

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	1.7 percent change Standard Error 1.7	-63.7 percent change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	-2.7 percent change Standard Error 1.6	-64.2 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: mITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis	-2.8 percent change Standard Error 1.5	-64.8 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=141 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis	-1.6 percent change Standard Error 1.7	-55.0 percent change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the mITT population with one baseline and at least one post-baseline Apo-B value on-treatment (Apo B mITT population).

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=70 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=140 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis	-2.1 percent change Standard Error 1.7	-55.9 percent change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	2.6 percent change Standard Error 1.6	-54.9 percent change Standard Error 1.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the mITT population with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis	2.6 percent change Standard Error 1.6	-56.0 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	2.0 percent change Standard Error 1.3	-39.5 percent change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo B ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=141 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	-3.3 percent change Standard Error 1.5	-54.6 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Non-HDL-C ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	-1.7 percent change Standard Error 1.4	-56.3 percent change Standard Error 1.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Total-C ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	-2.1 percent change Standard Error 1.1	-41.1 percent change Standard Error 0.8

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population.

Calculated LDL-C goal was defined as: * \<100 mg/dL (2.59 mmol/L) for heFH or non-FH participants who had a history of documented congestive heart disease (CHD), or * \<120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases (ischemic stroke, peripheral artery disease, chronic kidney disease or diabetes) or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in imputation model.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - ITT Analysis	10.2 percentage of participants	96.7 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population.

Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - On-Treatment Analysis	10.6 percentage of participants	97.9 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment were included in the imputation model.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis	2.5 percent change Standard Error 2.5	-39.5 percent change Standard Error 1.8

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	6.7 percent change Standard Error 3.7	-15.3 percent change Standard Error 2.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	2.1 percent change Standard Error 1.5	7.9 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=141 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis	-2.6 percent change Standard Error 1.6	1.4 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis	-0.5 percent change Standard Error 2.4	-41.9 percent change Standard Error 1.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	2.4 percent change Standard Error 3.7	-13.1 percent change Standard Error 2.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: HDL-C ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	-1.8 percent change Standard Error 1.2	4.7 percent change Standard Error 0.8

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo A1 ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=141 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis	-4.8 percent change Standard Error 1.1	1.5 percent change Standard Error 0.8

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted LS means and standard errors at Week 52 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=72 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis	-3.6 Percent change Standard Error 1.9	-62.5 Percent change Standard Error 1.4

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 52

Population: mITT population.

Adjusted LS means and standard errors at Week 52 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=71 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=143 Participants Alirocumab 75 mg SC injection Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 100 mg/dL (2.59 mmol/L) or ≥ 120 mg/dL (3.10 mmol/L) at Week 8 according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis	-3.4 Percent change Standard Error 1.7	-64.6 Percent change Standard Error 1.2

Adverse Events

Placebo Q2W

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Alirocumab 75 mg/ Up to 150 mg Q2W

Serious events: 10 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo Q2W n=72 participants at risk Participants exposed to placebo (for alirocumab) SC injection Q2W added to stable LMT (mean exposition of 50 weeks).	Alirocumab 75 mg/ Up to 150 mg Q2W n=143 participants at risk Participants exposed to alirocumab 75 mg /up to 150 mg SC injection Q2W added to stable LMT (mean exposition of 50 weeks).
Infections and infestations Nasopharyngitis	36.1% 26/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	45.5% 65/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Infections and infestations Pharyngitis	5.6% 4/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	6.3% 9/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Infections and infestations Influenza	8.3% 6/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	0.70% 1/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Immune system disorders Seasonal allergy	6.9% 5/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	0.70% 1/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Metabolism and nutrition disorders Diabetes mellitus	5.6% 4/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	8.4% 12/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Vascular disorders Hypertension	6.9% 5/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	6.3% 9/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Gastrointestinal disorders Dental caries	1.4% 1/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	6.3% 9/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Gastrointestinal disorders Abdominal pain upper	5.6% 4/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	2.8% 4/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Musculoskeletal and connective tissue disorders Back pain	5.6% 4/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	12.6% 18/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 6/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	2.8% 4/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.6% 4/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	0.70% 1/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
General disorders Injection site reaction	4.2% 3/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	12.6% 18/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Injury, poisoning and procedural complications Fall	6.9% 5/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	7.7% 11/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.
Injury, poisoning and procedural complications Contusion	4.2% 3/72 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.	5.6% 8/143 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Analysis was done on safety population that included randomized participants who actually received at least 1 dose or part of a dose of double-blind investigational medicinal product (IMP) injection.

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER