Study of Alirocumab (REGN727/SAR236553) in Patients With... | NCT01709500

NCT01709500

Status Module

Name	Class
Sanofi	INDUSTRY

Label	Type	Description	Intervention Names
Alirocumab 75 mg/up to 150 mg	Experimental	Alirocumab 75 mg every two weeks (Q2W) added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.	Drug: LMT (atorvastatin, simvastatin, or rosuvastatin) Drug: alirocumab
Placebo	Placebo Comparator	Placebo matched to alirocumab SC injection for 78-week treatment duration.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
LMT (atorvastatin, simvastatin, or rosuvastatin)	Drug		Alirocumab 75 mg/up to 150 mg
alirocumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--to--Treat (ITT) Analysis	Calculated LDL-C values were obtained using the Friedewald formula. 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.	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	Calculated LDL-C values were obtained using the Friedewald formula. 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).	From Baseline to Week 52

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients with heFH* who are not adequately controlled** with a maximally-tolerated daily dose*** of statin with or without other LMT, at a stable dose prior to the screening visit (week -2).

*Diagnosis of heFH must be made either by genotyping or by clinical criteria. For those patients not genotyped, the clinical diagnosis may be based on either the Simon Broome criteria for definite FH (Appendix 1) or the WHO/Dutch Lipid Network criteria with a score of >8 points (Appendix 2).

** "Not adequately controlled" is defined as LDL-C ≥70 mg/dL (1.81 mmol/L) at the screening visit (week -2) in patients with a history of documented CVD (Appendix 3), or LDL-C ≥100 mg/dL (2.59 mmol/L) at the screening visit (week -2) in patients without a history of documented CVD.

*** "Maximally-tolerated dose" is defined as (any of the following are acceptable):
- Rosuvastatin 20 mg or 40 mg daily
- Atorvastatin 40 mg or 80 mg daily
- Simvastatin 80 mg daily (if already on this dose for >1 year - see exclusion criterion #7)
Note: Patients who are not able to be on any of the above statin doses should be treated with the dose of daily atorvastatin, rosuvastatin, or simvastatin which is considered appropriate for the patient, according to the investigator's judgment. Some examples of acceptable reasons for a patient taking a lower statin dose include, but are not limited to: adverse effects on higher doses, advanced age, low body mass index, regional practices, local prescribing information, concomitant medications, co-morbid conditions such as impaired glucose tolerance/impaired fasting glucose. The reason(s) will be documented in the case report form (CRF).
Provide signed informed consent

Exclusion Criteria:

Patient without diagnosis of heFH made either by genotyping or by clinical criteria
LDL-C <70 mg/dL (<1.81 mmol/L) at the screening visit (week-2) in patients with history of documented cardiovascular disease
LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (week -2) in patients without history of documented cardiovascular disease
Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit (week -2) and from screening to randomization
Currently taking another statin than simvastatin, atorvastatin, or rosuvastatin
Simvastatin, atorvastatin, or rosuvastatin is not taken daily or not taken at a registered dose
Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for patients on simvastatin 80 mg for more than 1 year, who are eligible)
Use of fibrates, other than fenofibrate within 6 weeks of the screening visit (week-2) or between screening and randomization visits
Use of nutraceutical products or over-the-counter therapies that may affect lipids which have not been at a stable dose/amount for at least 4 weeks prior to the screening visit (week -2) or between screening and randomization visits
Use of red yeast rice products within 4 weeks of the screening visit (week-2), or between screening and randomization visits
Patient who has received plasmapheresis treatment within 2 months prior to the screening visit (week -2), or has plans to receive it during the study
Recent (within 3 months prior to the screening visit [week -2] or between screening and randomization visits) MI, unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack (TIA), carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease

(The inclusion/exclusion criteria provided above is not intended to contain all considerations relevant to a participant's potential participation in this clinical trial).

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

PubMed Identifier	Type	Citation	Retractions
34298554	Derived	Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.
30183102

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection every two weeks (Q2W) added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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 - Intent--to--Treat (ITT) Analysis

Calculated LDL-C values were obtained using the Friedewald formula. 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 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	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000166 OG00181

Title

Denominators

Categories

Title	Measurements
	OG000-48.7± 1.9 OG0012.8± 2.8

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 the placebo group using an appropriate contrast statement.	Mixed Models Analysis		<0.0001	Threshold for significance ≤ 0.05.	LS Mean Difference	-51.4			2-Sided	95	-58.1	-44.8				No	Superiority or Other

Secondary

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

Calculated LDL-C values were obtained using the Friedewald formula. 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).

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	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants

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 analysis).

ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

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

Calculated LDL-C values were obtained using the Friedewald formula. Adjusted LS means and standard errors at Week 12 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).

mITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein (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 analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 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).

mITT population

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 analyzed: participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 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).

mITT population

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 analyzed: participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

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

Calculated LDL-C values were obtained using the Friedewald formula. 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 analysis).

ITT population.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis

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 analysis).

ITT population.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

Percentage of Very High CV Risk Participants Reaching Calculated LDL--C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL--C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis

Adjusted percentages at Week 24 were obtained 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 (on-treatment analysis).

mITT population.

Posted

Number

percentage of participants

Up to week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

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

ITT population.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Reaching Calculated LDL--C <70 mg/dL (1.81 mmol/L) at Week 52 - On-Treatment Analysis

Adjusted percentages at Week 52 were obtained 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 (on-treatment analysis).

mITT population.

Posted

Number

percentage of participants

Up to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Participants analyzed: participants of the ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Participants analyzed: participants of the ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in 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 analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment.

Posted

Least Squares Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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 a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Lipoprotein (a) ITT population.

Posted

Mean

Standard Deviation

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Secondary

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

Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.

Fasting triglycerides ITT population.

Posted

Mean

Standard Error

percent change

From Baseline to Week 52

ID	Title	Description
OG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

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	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
OG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	meddra (17.0)	Systematic Assessment	EG0000 events0 affected167 at risk EG0011 affected81 at risk
Angina pectoris	Cardiac disorders	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk
Angina unstable	Cardiac disorders	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Cardiogenic shock	Cardiac disorders	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Coronary artery stenosis	Cardiac disorders	meddra (17.0)	Systematic Assessment	EG0001 events1 affected167 at risk EG0010 affected81 at risk
Myocardial infarction	Cardiac disorders	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Device dislocation	General disorders	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk
Non-Cardiac chest pain	General disorders	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Appendicitis	Infections and infestations	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk
Endocarditis	Infections and infestations	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Hepatitis a	Infections and infestations	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk
Lower respiratory tract infection	Infections and infestations	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Viral infection	Infections and infestations	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0011 affected81 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk
Syncope	Nervous system disorders	meddra (17.0)	Systematic Assessment	EG0000 affected167 at risk EG0011 affected81 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	meddra (17.0)	Systematic Assessment	EG0001 affected167 at risk EG0010 affected81 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Hradec Králové			Czechia

ID	Term
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006538	Heptanoic Acids
D005227	Fatty Acids
D008055	Lipids
D008148	Lovastatin
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D011083	Polycyclic Compounds
D013449	Sulfonamides
D000577	Amides
D005464	Fluorobenzenes
D006845	Hydrocarbons, Fluorinated
D006846	Hydrocarbons, Halogenated
D013450	Sulfones
D013457	Sulfur Compounds
D011743	Pyrimidines

ID	Title	Description
BG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
BG001	Placebo	Placebo matched to alirocumab SC injection for 78--week treatment duration.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Alirocumab 75 mg/up to 150 mg	Alirocumab 75 mg SC injection every two weeks (Q2W) added to stable dose of statin with or without LMT for 76 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.			10	167	65	167
EG001	Placebo	Placebo matched to alirocumab SC injection for 78-week treatment duration.			7	81	35	81

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	meddra (17.0)	Systematic Assessment	EG0009 affected167 at risk EG0011 affected81 at risk
Injection site reaction	General disorders	meddra (17.0)	Systematic Assessment	EG00018 affected167 at risk EG0016 affected81 at risk
Influenza	Infections and infestations	meddra (17.0)	Systematic Assessment	EG00024 affected167 at risk EG0016 affected81 at risk
Nasopharyngitis	Infections and infestations	meddra (17.0)	Systematic Assessment	EG00018 affected167 at risk EG00116 affected81 at risk
Myalgia	Musculoskeletal and connective tissue disorders	meddra (17.0)	Systematic Assessment	EG00010 affected167 at risk EG0015 affected81 at risk
Headache	Nervous system disorders	meddra (17.0)	Systematic Assessment	EG00014 affected167 at risk EG0017 affected81 at risk

ID	Term
D000069059	Atorvastatin
D019821	Simvastatin
D000068718	Rosuvastatin Calcium
C571059	alirocumab