Trial Outcomes & Findings for Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term) (NCT NCT01507831)

Last Updated: 2015-12-22

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2341 participants

Primary outcome timeframe

Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Results posted on

2015-12-22

Participant Flow

The study was conducted at 320 centers in 27 countries. Overall, 5144 participants were screened between January 2012 and March 2013, 2801 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. In addition 2 participants received study drug but did not undergo randomization. They were excluded from analysis.

Randomization was stratified as per diagnosis of heterozygous familial hypercholesterolemia (heFH), prior history of myocardial infarction (MI) or ischemic stroke, intensity of statin treatment and geographic region. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo:alirocumab).

Participant milestones

Participant milestones
Measure	Placebo Q2W Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable lipid modifying therapy (LMT) for 78 weeks.	Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Study STARTED	788	1553
Overall Study Treated	788	1550
Overall Study COMPLETED	595	1113
Overall Study NOT COMPLETED	193	440

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Q2W Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable lipid modifying therapy (LMT) for 78 weeks.	Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Overall Study Randomized but not treated	0	3
Overall Study Adverse Event	48	113
Overall Study Death	6	2
Overall Study Poor compliance to protocol	38	60
Overall Study Physician Decision	0	4
Overall Study Participant moved	5	19
Overall Study Consent withdrawn by participant	34	72
Overall Study Related to study drug administration	5	14
Overall Study Last visit outside protocol visit window	51	143
Overall Study Selection criteria finally not met	0	1
Overall Study Site closure	0	3
Overall Study Potential lost to follow-up	3	0
Overall Study Other	3	6

Baseline Characteristics

Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Q2W n=788 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1553 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.	Total n=2341 Participants Total of all reporting groups
Age, Continuous	60.6 years STANDARD_DEVIATION 10.4 • n=5 Participants	60.4 years STANDARD_DEVIATION 10.4 • n=7 Participants	60.5 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	314 Participants n=5 Participants	570 Participants n=7 Participants	884 Participants n=5 Participants
Sex: Female, Male Male	474 Participants n=5 Participants	983 Participants n=7 Participants	1457 Participants n=5 Participants
Calculated LDL-C in mg/dL	121.9 mg/dL STANDARD_DEVIATION 41.4 • n=5 Participants	122.7 mg/dL STANDARD_DEVIATION 42.6 • n=7 Participants	122.4 mg/dL STANDARD_DEVIATION 42.2 • n=5 Participants
Calculated LDL-C in mmol/L	3.157 mmol/L STANDARD_DEVIATION 1.073 • n=5 Participants	3.178 mmol/L STANDARD_DEVIATION 1.102 • n=7 Participants	3.171 mmol/L STANDARD_DEVIATION 1.092 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Population: Safety population: all randomized participants who received at least one dose or part of a dose of a study drug (treated).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=788 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1550 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percentage of Participants Who Experienced Adverse Events (AEs) Any AE	82.5 percentage of participants	81.0 percentage of participants
Percentage of Participants Who Experienced Adverse Events (AEs) Any Serious AE	19.5 percentage of participants	18.7 percentage of participants
Percentage of Participants Who Experienced Adverse Events (AEs) Any AE leading to death	1.3 percentage of participants	0.5 percentage of participants
Percentage of Participants Who Experienced Adverse Events (AEs) Any AE leading to treatment discontinuation	5.8 percentage of participants	7.2 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment were used in the model (ITT analysis).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis	0.8 percent change Standard Error 1.0	-61.0 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 (i.e. up to 21 days after last injection) (on-treatment analysis).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=777 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1523 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	0.7 percent change Standard Error 1.0	-62.8 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	1.5 percent change Standard Error 1.0	-63.3 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=777 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1523 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis	1.4 percent change Standard Error 1.0	-64.2 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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

Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 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=652 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1278 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis	3.5 percent change Standard Error 1.1	-57.8 percent change Standard Error 0.8

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=753 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1468 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis	1.2 percent change Standard Error 1.0	-52.8 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=743 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1444 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis	1.2 percent change Standard Error 0.9	-54.3 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	0.7 percent change Standard Error 0.9	-51.6 percent change Standard Error 0.6

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=777 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1523 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis	0.6 percent change Standard Error 0.9	-53.1 percent change Standard Error 0.6

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	-0.3 percent change Standard Error 0.7	-37.8 percent change Standard Error 0.5

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=753 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1468 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	0.5 percent change Standard Error 0.9	-55.5 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	0.9 percent change Standard Error 0.8	-53.7 percent change Standard Error 0.6

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	0.2 percent change Standard Error 0.6	-38.8 percent change Standard Error 0.4

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT population.

Very high CV risk: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents or non- Familial Hypercholesterolemia (FH). High CV risk: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to \<60 ml/minute/1.73 m\^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of \>2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or family history of premature CHD). 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 52 regardless of status on- or off-treatment were included in imputation model.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis	8.5 percentage of participants	80.7 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

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 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=777 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1523 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis	8.5 percentage of participants	82.8 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT population.

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 52 regardless of status on- or off-treatment were included in the imputation model.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	8.0 percentage of participants	79.3 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: mITT population.

Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 52 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=777 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1523 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	8.0 percentage of participants	81.2 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment were included in the imputation model.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis	-3.7 percent change Standard Error 1.0	-29.3 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	-0.6 percent change Standard Error 0.5	4.0 percent change Standard Error 0.4

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	1.8 percent change Standard Error 1.2	-15.6 percent change Standard Error 0.8

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=753 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1468 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis	1.2 percent change Standard Error 0.6	4.0 percent change Standard Error 0.4

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on-or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis	-3.1 percent change Standard Error 1.0	-28.2 percent change Standard Error 0.7

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	0.2 percent change Standard Error 0.5	5.8 percent change Standard Error 0.4

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	1.2 percent change Standard Error 1.1	-16.7 percent change Standard Error 0.8

SECONDARY outcome

Timeframe: From Baseline to Week 52

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 52 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=753 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1468 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis	0.6 percent change Standard Error 0.5	4.6 percent change Standard Error 0.3

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 all 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=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis	4.4 percent change Standard Error 1.2	-56.8 percent change Standard Error 0.8

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 52

Population: mITT population.

Adjusted LS means and standard errors at Week 52 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=777 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1523 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis	4.6 percent change Standard Error 1.1	-59.9 percent change Standard Error 0.8

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 78

Population: ITT population.

Adjusted LS means and standard errors at Week 78 from MMRM model including all available post-baseline data from Week 4 to Week 78 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=780 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1530 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis	3.6 percent change Standard Error 1.3	-52.4 percent change Standard Error 0.9

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 78

Population: mITT population.

Adjusted LS means and standard errors at Week 78 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 78 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=777 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1523 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis	3.9 percent change Standard Error 1.2	-58.0 percent change Standard Error 0.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Population: Safety population.

CV events included coronary heart disease (CHD) death; non-fatal myocardial infarction (MI); fatal and non-fatal ischemic stroke; unstable angina requiring hospitalization; congestive heart failure (CHF) requiring hospitalization; ischemia-driven coronary revascularization procedure. Reported events are CV events as confirmed by an independent Clinical Events Committee (CEC) that occurred during the treatment emergent period ( i.e. from first dose up to the last dose of study drug + 70 days).

Outcome measures

Outcome measures
Measure	Placebo Q2W n=788 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1550 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percentage of Participants Who Experienced Cardiovascular (CV) Events	5.1 percentage of participants	4.6 percentage of participants

POST_HOC outcome

Timeframe: Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Population: Safety population.

Major adverse CV events were defined as all adverse CV events except Congestive heart failure (CHF) requiring hospitalization; and ischemia-driven coronary revascularization procedure.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=788 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1550 Participants Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Percentage of Participants Who Experienced Major Adverse CV Events	3.3 percentage of participants	1.7 percentage of participants

Adverse Events

Placebo Q2W

Serious events: 154 serious events

Other events: 366 other events

Deaths: 0 deaths

Alirocumab 150 mg Q2W

Serious events: 290 serious events

Other events: 707 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo Q2W n=788 participants at risk Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.	Alirocumab 150 mg Q2W n=1550 participants at risk Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Infections and infestations Nasopharyngitis	13.1% 103/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	13.5% 209/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Infections and infestations Upper respiratory tract infection	8.6% 68/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	7.4% 114/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Infections and infestations Urinary tract infection	6.9% 54/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.6% 87/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Infections and infestations Influenza	5.5% 43/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.7% 88/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Infections and infestations Bronchitis	5.1% 40/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.4% 83/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Nervous system disorders Headache	5.6% 44/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	4.9% 76/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Gastrointestinal disorders Diarrhoea	5.7% 45/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.7% 89/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Musculoskeletal and connective tissue disorders Back pain	6.6% 52/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.4% 84/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Musculoskeletal and connective tissue disorders Myalgia	2.9% 23/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.4% 84/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
Musculoskeletal and connective tissue disorders Arthralgia	6.6% 52/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.2% 80/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).
General disorders Injection site reaction	4.2% 33/788 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).	5.9% 91/1550 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 86 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).

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