Efficacy and Safety of Alirocumab (SAR236553/REGN727) Ver... | NCT01617655

ID	Type	Description	Link
U1111-1128-5459	Other Identifier	UTN
2012-001096-37	EudraCT Number

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Ver... | NCT01617655 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo Q2W	Placebo Comparator	Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.	Drug: Placebo (for alirocumab) Drug: Lipid Modifying Therapy (LMT)
Alirocumab 150 mg Q2W	Experimental	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.	Drug: Alirocumab Drug: Lipid Modifying Therapy (LMT)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Alirocumab	Drug	Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis	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).	From Baseline to Week 52

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	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).	From Baseline to Week 52

Other Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis	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.	From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis

Contacts/Locations Module

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840742		Bell Gardens	California	90201	United States
Investigational Site Number 840703

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24842558	Background	Kastelein JJ, Robinson JG, Farnier M, Krempf M, Langslet G, Lorenzato C, Gipe DA, Baccara-Dinet MT. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther. 2014 Jun;28(3):281-9. doi: 10.1007/s10557-014-6523-z.
27618825

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo Q2W	Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.
FG001	Alirocumab 150 mg Q2W

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Adverse Event		FG0002 subjects FG0013 subjects
Poor compliance to protocol		FG0001 subjects FG0014 subjects
Participants moved		FG0000 subjects FG0014 subjects
Consent withdrawn by participant		FG0001 subjects FG0011 subjects
Last visit outside protocol visit window		FG0001 subjects FG00110 subjects
Site closure		FG0003 subjects FG0015 subjects
Other than specified above		FG0001 subjects FG0012 subjects

Arm/Group Information

ID	Title	Description
BG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
BG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00052.1± 11.2 BG00149.8± 14.2 BG00250.6± 13.3

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00013 BG00137 BG002

Calculated LDL-C in mg/dL

Calculated LDL-C from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000201± 43.4 BG001196.3± 57.9

Calculated low density lipoprotein cholesterol (LDL-C) in mmol/L

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0005.205± 1.125 BG0015.083± 1.499 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis

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).

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

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG00035 OG00171

Title

Denominators

Categories

Title	Measurements
	OG000-6.6± 4.9 OG001-45.7± 3.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Alirocumab group was compared to placebo group using an appropriate contrast statement.	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-39.1			2-Sided	95	-51.1	-27.1			Alirocumab vs Placebo	No	Superiority or Other

Secondary

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

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).

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

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

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.

ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

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.

mITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis

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.

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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis

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).

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

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis

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.

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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis

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).

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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

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.

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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apo B at Week 12 - ITT Analysis

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.

Apo B ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis

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.

Non-HDL-C ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total-C at Week 12 - ITT Analysis

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.

Total-C ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis

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.

ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

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 a 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.

ITT population.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Secondary

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

Adjusted percentages at Week 24 from a 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.

mITT population.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis

Adjusted means and standard errors at Week 24 from a 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.

ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis

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.

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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

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.

ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis

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.

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).

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis

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.

ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis

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.

HDL-C ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis

ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis

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.

Apo A-1 ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis

Adjusted percentages at Week 24 from multiple imputation approach including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

ITT population.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis

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.

mITT population.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis

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.

mITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis

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.

ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 78

ID	Title	Description
OG000	Placebo Q2W	Participants exposed to placebo Q2W on top of stable LMT (mean exposure of 78 weeks).
OG001	Alirocumab 150 Q2W	Participants exposed to Alirocumab 150 mg Q2W on top of stable LMT (mean exposure of 78 weeks).

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis

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.

mITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 78

ID	Title	Description
OG000	Placebo Q2W	Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
OG001	Alirocumab 150 mg Q2W	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Q2W	Participants exposed to placebo Q2W on top of stable LMT (mean exposure of 71 weeks).			4	35	20	35
EG001	Alirocumab 150 Q2W	Participants exposed to Alirocumab 150 mg Q2W on top of stable LMT (mean exposure of 68 weeks).			10	72	39	72

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Diverticulitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected35 at risk EG0010 affected72 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0012 affected72 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Angina pectoris	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected35 at risk EG0011 affected72 at risk
Cardiac failure	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Biliary colic	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected35 at risk EG0010 affected72 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected35 at risk EG0010 affected72 at risk
Renal failure	Renal and urinary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0011 affected72 at risk
Renal colic	Renal and urinary disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected35 at risk EG0010 affected72 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0004 affected35 at risk EG00110 affected72 at risk
Influenza	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 affected35 at risk EG0019 affected72 at risk
Bronchitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0002 affected35 at risk EG0014 affected72 at risk
Urinary tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0015 affected72 at risk
Sinusitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0002 affected35 at risk EG0014 affected72 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0014 affected72 at risk
Dizziness	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0015 affected72 at risk
Headache	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0015 affected72 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 17.1	Systematic Assessment	EG0002 affected35 at risk EG0011 affected72 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0003 affected35 at risk EG0014 affected72 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0014 affected72 at risk
Nausea	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0002 affected35 at risk EG0012 affected72 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0002 affected35 at risk EG0010 affected72 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0003 affected35 at risk EG0014 affected72 at risk
Injection site reaction	General disorders	MedDRA 17.1	Systematic Assessment	EG0002 affected35 at risk EG0016 affected72 at risk
Fatigue	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected35 at risk EG0015 affected72 at risk
Blood uric acid increased	Investigations	MedDRA 17.1	Systematic Assessment	EG0002 affected35 at risk EG0010 affected72 at risk

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-38.9			2-Sided	95	-51	-26.9			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-40.3			2-Sided	95	-51.4	-29.3			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-40.3			2-Sided	95	-51.4	-29.2			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-30.3			2-Sided	95	-39.7	-20.9			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-30.2			2-Sided	95	-39.7	-20.7			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-35.8			2-Sided	95	-46.3	-25.3			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-35.5			2-Sided	95	-46.2	-24.9			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-28.4			2-Sided	95	-37.3	-19.6			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-30.2			2-Sided	95	-39.2	-21.1			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-34.5			2-Sided	95	-44.8	-24.1			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-27.8			2-Sided	95	-36.2	-19.4			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS mean difference	-39.1			2-Sided	95	-53.6	-24.6			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Regression, Logistic	Multiple imputation approach followed by logistic regression model.	0.0016	Threshold for significance ≤ 0.05.	Odds Ratio (OR)	11.7			2-Sided	95	2.5	53.5			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Regression, Logistic	Multiple imputation approach followed by logistic regression model.	0.0014	Threshold for significance ≤ 0.05.	Odds Ratio (OR)	11.9			2-Sided	95	2.6	54.9			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Regression, Robust	Multiple imputation approach followed by robust regression model.	0.0164	Threshold for significance ≤ 0.05.	Adjusted Mean Difference	-14.8			2-Sided	95	-26.9	-2.7			Alirocumab vs Placebo	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).	Mixed Models Analysis		0.2745	Threshold for significance ≤ 0.05.	LS mean difference	3.7			2-Sided	95	-2.9	10.2			Alirocumab vs Placebo	No	Superiority or Other

ID	Term
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases