Trial Outcomes & Findings for Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I) (NCT NCT01644175)

Last Updated: 2015-11-06

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

316 participants

Primary outcome timeframe

From Baseline to Week 52

Results posted on

2015-11-06

Participant Flow

The study was conducted at 76 centers in the United States of America. Overall, 640 participants were screened between July 2012 and February 2013, 324 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.

Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke, and intensity of statin treatment. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo: alirocumab) after confirmation of selection criteria. 316 participants were randomized.

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 52 weeks.	Alirocumab 75/150 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 LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Study STARTED	107	209
Overall Study Treated	107	207
Overall Study COMPLETED	75	156
Overall Study NOT COMPLETED	32	53

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 52 weeks.	Alirocumab 75/150 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 LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Study Randomized But Not Treated	0	2
Overall Study Adverse Event	8	13
Overall Study Death	1	2
Overall Study Poor compliance to protocol	9	10
Overall Study Physician Decision	1	2
Overall Study Participant Moved	1	2
Overall Study Consent withdrawn by participant	3	4
Overall Study Related to Autoinjector Administration	2	1
Overall Study Last visit outside protocol visit window	4	11
Overall Study Selection criteria finally not met	0	1
Overall Study Site closure	2	2
Overall Study Lost to Follow-up	1	0
Overall Study Other than specified above	0	3

Baseline Characteristics

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Q2W n=107 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=209 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.	Total n=316 Participants Total of all reporting groups
Age, Continuous	63.0 years STANDARD_DEVIATION 8.8 • n=5 Participants	63.0 years STANDARD_DEVIATION 9.5 • n=7 Participants	63.0 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	78 Participants n=7 Participants	108 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	131 Participants n=7 Participants	208 Participants n=5 Participants
Calculated LDL-C in mmol/L	2.746 mmol/L STANDARD_DEVIATION 0.915 • n=5 Participants	2.595 mmol/L STANDARD_DEVIATION 0.764 • n=7 Participants	2.646 mmol/L STANDARD_DEVIATION 0.820 • n=5 Participants
Calculated LDL-C in mg/dL	106.0 mg/dL STANDARD_DEVIATION 35.3 • n=5 Participants	100.2 mg/dL STANDARD_DEVIATION 29.5 • n=7 Participants	102.2 mg/dL STANDARD_DEVIATION 31.6 • n=5 Participants

PRIMARY 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.

Outcome measures

Outcome measures
Measure	Placebo Q2W n=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis	-2.3 percent change Standard Error 2.7	-48.2 percent change Standard Error 1.9

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=105 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=204 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	-0.8 percent change Standard Error 2.6	-50.7 percent change Standard Error 1.9

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: 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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	1.1 percent change Standard Error 2.5	-46.3 percent change Standard Error 1.8

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=105 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=204 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis	1.7 percent change Standard Error 2.5	-47.6 percent change Standard Error 1.8

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=96 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=185 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis	-0.9 percent change Standard Error 2.3	-36.7 percent change Standard Error 1.6

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 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=93 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=181 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis	-0.4 percent change Standard Error 2.3	-37.9 percent change Standard Error 1.6

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	-1.6 percent change Standard Error 2.5	-39.1 percent change Standard Error 1.8

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=105 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=204 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis	-0.5 percent change Standard Error 2.5	-40.9 percent change Standard Error 1.8

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	-2.9 percent change Standard Error 1.8	-27.9 percent change Standard Error 1.3

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=96 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=185 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	3.4 percent change Standard Error 2.3	-34.8 percent change Standard Error 1.6

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	2.6 percent change Standard Error 2.6	-37.4 percent change Standard Error 1.8

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	0.9 percent change Standard Error 2.0	-25.4 percent change Standard Error 1.4

SECONDARY 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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis	0.5 percent change Standard Error 3.6	-42.5 percent change Standard Error 2.5

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	9.0 percentage of participants	75.0 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 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=105 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=204 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
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	77.5 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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis	-5.9 percent change Standard Error 2.8	-20.5 percent change Standard Error 2.0

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	-3.8 percent change Standard Error 1.5	3.5 percent change Standard Error 1.1

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted means and standard errors at Week 24 from multiple imputation approach followed be 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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	-5.4 percent change Standard Error 3.2	-6.0 percent change Standard Error 2.3

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment (Apo A-1 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=96 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=185 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apolipoprotein A-1 at Week 24 - ITT Analysis	-2.5 percent change Standard Error 1.2	3.3 percent change Standard Error 0.9

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis	0.0 percent change Standard Error 2.7	-19.7 percent change Standard Error 1.9

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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	-2.4 percent change Standard Error 1.4	6.7 percent change Standard Error 1.0

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 a 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=106 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=205 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	3.0 percent change Standard Error 2.9	-11.3 percent change Standard Error 2.0

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: Apo A-1 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=96 Participants Placebo (for alirocumab) SC injection Q2W added to stable LMT for 52 weeks.	Alirocumab 75/150 mg Q2W n=185 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 ≥70 mg/dL (1.81 mmol/L) at Week 8.
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis	-1.8 percent change Standard Error 1.3	3.8 percent change Standard Error 0.9

Adverse Events

Placebo Q2W

Serious events: 14 serious events

Other events: 31 other events

Deaths: 0 deaths

Alirocumab 75 /up to 150 mg Q2W

Serious events: 26 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo Q2W n=107 participants at risk Participants exposed to placebo (for alirocumab) SC injection Q2W added to stable LMT (mean exposition of 45 weeks).	Alirocumab 75 /up to 150 mg Q2W n=207 participants at risk Participants exposed to alirocumab 75 mg /up to 150 mg SC injection Q2W added to stable LMT (mean exposition of 46 weeks).
Infections and infestations Upper respiratory tract infection	10.3% 11/107 • 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).	7.7% 16/207 • 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).
Infections and infestations Nasopharyngitis	4.7% 5/107 • 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).	7.2% 15/207 • 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).
Infections and infestations Urinary tract infection	3.7% 4/107 • 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).	6.3% 13/207 • 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).
Infections and infestations Sinusitis	3.7% 4/107 • 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).	5.3% 11/207 • 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).
Nervous system disorders Dizziness	5.6% 6/107 • 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).	5.3% 11/207 • 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).
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 8/107 • 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).	3.9% 8/207 • 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).
General disorders Injection site reaction	2.8% 3/107 • 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).	5.3% 11/207 • 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).

Additional Information

Trial Transparency Team

Sanofi

Email: Contact [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