Trial Outcomes & Findings for Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy (NCT NCT01623115)

Last Updated: 2016-02-08

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

486 participants

Primary outcome timeframe

From Baseline to Week 52

Results posted on

2016-02-08

Participant Flow

The study was conducted at 89 centers in 14 countries. A total of 597 participants were screened between July 2012 and April 2013, 111 of whom were screen failures.

Randomization was stratified according to prior history of myocardial infarction or ischemic stroke, intensity of statin treatment \& geographic region. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in 1:2 (placebo:alirocumab) after confirmation of selection criteria. 486 participants were randomized.

Participant milestones

Participant milestones
Measure	Placebo Placebo for alirocumab subcutaneous (SC) injection every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 70 mg/dL (1.81 mmol/L) at Week 8.
Overall Study STARTED	163	323
Overall Study Treated	163	322
Overall Study COMPLETED	130	246
Overall Study NOT COMPLETED	33	77

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo for alirocumab subcutaneous (SC) injection every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 70 mg/dL (1.81 mmol/L) at Week 8.
Overall Study Randomized but not treated	0	1
Overall Study Physician Decision	1	0
Overall Study Participants moved	1	5
Overall Study Adverse Event	10	13
Overall Study Poor compliance to protocol	4	10
Overall Study Consent withdrawn by participant	2	6
Overall Study Related to study drug administration	0	2
Overall Study Last visit outside protocol visit window	14	26
Overall Study Site closure	1	7
Overall Study Death	0	4
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 Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=323 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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=486 Participants Total of all reporting groups
Age, Continuous	51.7 years STANDARD_DEVIATION 12.3 • n=5 Participants	52.1 years STANDARD_DEVIATION 12.9 • n=7 Participants	51.9 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	143 Participants n=7 Participants	212 Participants n=5 Participants
Sex: Female, Male Male	94 Participants n=5 Participants	180 Participants n=7 Participants	274 Participants n=5 Participants
Calculated LDL-C in mg/dL	144.4 mg/dL STANDARD_DEVIATION 46.8 • n=5 Participants	144.8 mg/dL STANDARD_DEVIATION 51.1 • n=7 Participants	144.6 mg/dL STANDARD_DEVIATION 49.7 • n=5 Participants
Calculated LDL-C in mmol/L	3.739 mmol/L STANDARD_DEVIATION 1.213 • n=5 Participants	3.749 mmol/L STANDARD_DEVIATION 1.325 • n=7 Participants	3.746 mmol/L STANDARD_DEVIATION 1.287 • 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	9.1 percent change Standard Error 2.2	-48.8 percent change Standard Error 1.6

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 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=321 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	8.8 percent change Standard Error 2.2	-49.3 percent change Standard Error 1.6

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	5.7 percent change Standard Error 2	-43.5 percent change Standard Error 1.4

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=321 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	5.7 percent change Standard Error 2	-43.9 percent change Standard Error 1.4

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 n=160 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=309 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 B (Apo B) at Week 24 - ITT Analysis	4.7 percent change Standard Error 1.6	-41.1 percent change Standard Error 1.2

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 n=159 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=308 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	4.5 percent change Standard Error 1.7	-41.4 percent change Standard Error 1.2

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	9.6 percent change Standard Error 2	-42.8 percent change Standard Error 1.4

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=321 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	9.4 percent change Standard Error 2	-43.3 percent change Standard Error 1.4

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	7.3 percent change Standard Error 1.5	-31.4 percent change Standard Error 1.1

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 n=160 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=309 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	3.1 percent change Standard Error 1.5	-34.5 percent change Standard Error 1.1

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	5.3 percent change Standard Error 1.8	-38.4 percent change Standard Error 1.3

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	4.1 percent change Standard Error 1.4	-28.3 percent change Standard Error 1

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	9 percent change Standard Error 2.6	-47.1 percent change Standard Error 1.9

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT population.

Very high CV risk participants: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents. High CV risk participants: 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 a family history of premature CHD). Adjusted percentages at Week 24 were obtained from multiple imputation approach 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis	2.4 percentage of participants	72.2 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: mITT population.

Adjusted percentages at Week 24 from multiple imputation approach 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=321 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 Very High CV Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - On- Treatment Analysis	2.4 percentage of participants	73 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT population.

Adjusted percentages at Week 24 from multiple imputation approach 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	0.8 percentage of participants	59.8 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=321 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	0.8 percentage of participants	60.1 percentage of participants

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	-7.5 percent change Standard Error 2	-25.2 percent change Standard Error 1.4

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	0.8 percent change Standard Error 1.2	8.8 percent change Standard Error 0.9

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Outcome measures

Outcome measures
Measure	Placebo n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	6.3 percent change Standard Error 2.2	-9.6 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 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 n=160 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=309 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 (Apo A-1) at Week 24 - ITT Analysis	0.3 percent change Standard Error 1	5 percent change Standard Error 0.7

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	-3.9 percent change Standard Error 1.8	-21.2 percent change Standard Error 1.3

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	2.1 percent change Standard Error 1.2	6.4 percent change Standard Error 0.8

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT population.

Outcome measures

Outcome measures
Measure	Placebo n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	1.7 percent change Standard Error 2.2	-8 percent change Standard Error 1.6

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 n=160 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=309 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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	0.1 percent change Standard Error 1	2.9 percent change Standard Error 0.7

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=321 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 - On-Treatment Analysis	9.1 percent change Standard Error 2.6	-48.1 percent change Standard Error 1.9

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Week 78

Population: ITT population.

Adjusted LS means and standard errors at Week 78 from MMRM 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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=322 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 78 - ITT Analysis	11.5 percent change Standard Error 2.8	-40.3 percent change Standard Error 2.0

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 n=163 Participants Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.	Alirocumab 75 mg/Up to 150 mg Q2W n=321 Participants Alirocumab 75 mg SC injection Q2W on top of stable LMT for 78 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 78 - On-Treatment Analysis	14.0 percent change Standard Error 2.8	-43.7 percent change Standard Error 2.0

Adverse Events

Placebo

Serious events: 22 serious events

Other events: 70 other events

Deaths: 0 deaths

Alirocumab 75/Up to 150 mg Q2W

Serious events: 44 serious events

Other events: 142 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=163 participants at risk Participants exposed to placebo Q2W on top of stable LMT (mean exposure of 72 weeks).	Alirocumab 75/Up to 150 mg Q2W n=322 participants at risk Participants exposed to Alirocumab 75 mg/Up to 150 mg Q2W on top of stable LMT (mean exposure of 72 weeks).
Infections and infestations Nasopharyngitis	7.4% 12/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	11.2% 36/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Upper respiratory tract infection	8.6% 14/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	6.8% 22/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Influenza	5.5% 9/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	6.2% 20/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Sinusitis	4.3% 7/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.3% 17/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Infections and infestations Bronchitis	5.5% 9/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	3.1% 10/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Nervous system disorders Headache	5.5% 9/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	4.7% 15/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Musculoskeletal and connective tissue disorders Arthralgia	5.5% 9/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	6.2% 20/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Musculoskeletal and connective tissue disorders Back pain	4.3% 7/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	5.6% 18/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
Musculoskeletal and connective tissue disorders Myalgia	6.7% 11/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	1.9% 6/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).
General disorders Injection site reaction	11.0% 18/163 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).	12.4% 40/322 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug. Reported adverse events are treatment-emergent that is AEs that developed/worsened during the 'treatment-emergent period' (from the first double-blind injection up to the day of the last injection + 70 days or up to first intake in the extension study, whichever came first).

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