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Trial record 2 of 2 for:    efc12492

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 (ODYSSEY FH I)

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ClinicalTrials.gov Identifier: NCT01623115
Recruitment Status : Completed
First Posted : June 19, 2012
Results First Posted : November 4, 2015
Last Update Posted : February 8, 2016
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hypercholesterolemia
Interventions Drug: Alirocumab
Drug: Placebo (for alirocumab)
Drug: Lipid Modifying Therapy (LMT)
Enrollment 486
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description Placebo for alirocumab subcutaneous (SC) injection every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks. 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.
Period Title: Overall Study
Started 163 [1] 323 [1]
Treated 163 322
Completed 130 246
Not Completed 33 77
Reason Not Completed
Randomized but not treated             0             1
Physician Decision             1             0
Participants moved             1             5
Adverse Event             10             13
Poor compliance to protocol             4             10
Consent withdrawn by participant             2             6
Related to study drug administration             0             2
Last visit outside protocol visit window             14             26
Site closure             1             7
Death             0             4
Other than specified above             0             3
[1]
Randomized
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W Total
Hide Arm/Group Description Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks. 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 of all reporting groups
Overall Number of Baseline Participants 163 323 486
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 163 participants 323 participants 486 participants
51.7  (12.3) 52.1  (12.9) 51.9  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 323 participants 486 participants
Female
69
  42.3%
143
  44.3%
212
  43.6%
Male
94
  57.7%
180
  55.7%
274
  56.4%
Calculated LDL-C in mg/dL   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 163 participants 323 participants 486 participants
144.4  (46.8) 144.8  (51.1) 144.6  (49.7)
[1]
Measure Description: Calculated LDL-C from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).
Calculated LDL-C in mmol/L  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 163 participants 323 participants 486 participants
3.739  (1.213) 3.749  (1.325) 3.746  (1.287)
1.Primary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
Hide Description 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).
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on­ or off-treatment.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
9.1  (2.2) -48.8  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Alirocumab group was compared to placebo group using an appropriate contrast statement.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -57.9
Confidence Interval (2-Sided) 95%
-63.3 to -52.6
Estimation Comments Alirocumab vs Placebo
2.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Hide Description 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).
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 321
Least Squares Mean (Standard Error)
Unit of Measure: percent change
8.8  (2.2) -49.3  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -58.1
Confidence Interval (2-Sided) 95%
-63.5 to -52.7
Estimation Comments Alirocumab vs Placebo
3.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 12 from MMRM including all available post­baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.7  (2) -43.5  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -49.2
Confidence Interval (2-Sided) 95%
-53.9 to -44.5
Estimation Comments Alirocumab vs Placebo
4.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Hide Description 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).
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 321
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.7  (2) -43.9  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -49.5
Confidence Interval (2-Sided) 95%
-54.2 to -44.8
Estimation Comments Alirocumab vs Placebo
5.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 from MMRM model including all available post­baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 160 309
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.7  (1.6) -41.1  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -45.8
Confidence Interval (2-Sided) 95%
-49.8 to -41.8
Estimation Comments Alirocumab vs Placebo
6.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
Hide Description 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).
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment (Apo B mITT population).
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 159 308
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.5  (1.7) -41.4  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -45.9
Confidence Interval (2-Sided) 95%
-49.9 to -41.8
Estimation Comments Alirocumab vs Placebo
7.Secondary Outcome
Title Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
9.6  (2) -42.8  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -52.4
Confidence Interval (2-Sided) 95%
-57.2 to -47.6
Estimation Comments Alirocumab vs Placebo
8.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
Hide Description 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).
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants of the mITT population with one baseline and at least one post-baseline non-HDL­C value on-treatment (non-HDL-C mITT population).
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 321
Least Squares Mean (Standard Error)
Unit of Measure: percent change
9.4  (2) -43.3  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -52.6
Confidence Interval (2-Sided) 95%
-57.5 to -47.8
Estimation Comments Alirocumab vs Placebo
9.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
7.3  (1.5) -31.4  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -38.7
Confidence Interval (2-Sided) 95%
-42.4 to -35
Estimation Comments Alirocumab vs Placebo
10.Secondary Outcome
Title Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Apo B ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 160 309
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.1  (1.5) -34.5  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -37.5
Confidence Interval (2-Sided) 95%
-41.2 to -33.9
Estimation Comments Alirocumab vs Placebo
11.Secondary Outcome
Title Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
non-HDL-C ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.3  (1.8) -38.4  (1.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -43.7
Confidence Interval (2-Sided) 95%
-48 to -39.4
Estimation Comments Alirocumab vs Placebo
12.Secondary Outcome
Title Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.1  (1.4) -28.3  (1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -32.5
Confidence Interval (2-Sided) 95%
-35.7 to -29.2
Estimation Comments Alirocumab vs Placebo
13.Secondary Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
9  (2.6) -47.1  (1.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -56.2
Confidence Interval (2-Sided) 95%
-62.4 to -50
Estimation Comments Alirocumab vs Placebo
14.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Measure Type: Number
Unit of Measure: percentage of participants
2.4 72.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 156
Confidence Interval (2-Sided) 95%
48.9 to 498.1
Estimation Comments Alirocumab vs Placebo
15.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 321
Measure Type: Number
Unit of Measure: percentage of participants
2.4 73
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 156.6
Confidence Interval (2-Sided) 95%
49.7 to 493.7
Estimation Comments Alirocumab vs Placebo
16.Secondary Outcome
Title Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Hide Description 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.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Measure Type: Number
Unit of Measure: percentage of participants
0.8 59.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 244.9
Confidence Interval (2-Sided) 95%
34.4 to 1744.4
Estimation Comments Alirocumab vs Placebo
17.Secondary Outcome
Title Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Hide Description 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.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 321
Measure Type: Number
Unit of Measure: percentage of participants
0.8 60.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 240
Confidence Interval (2-Sided) 95%
33.9 to 1700.7
Estimation Comments Alirocumab vs Placebo
18.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Mean (Standard Error)
Unit of Measure: percent change
-7.5  (2) -25.2  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -17.7
Confidence Interval (2-Sided) 95%
-22.6 to -12.9
Estimation Comments Alirocumab vs Placebo
19.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.8  (1.2) 8.8  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 8
Confidence Interval (2-Sided) 95%
5 to 11
Estimation Comments Alirocumab vs Placebo
20.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Mean (Standard Error)
Unit of Measure: percent change
6.3  (2.2) -9.6  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance was ≤ 0.05.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -16
Confidence Interval (2-Sided) 95%
-21.3 to -10.6
Estimation Comments Alirocumab vs Placebo
21.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 160 309
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.3  (1) 5  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0002
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
2.3 to 7.2
Estimation Comments Alirocumab vs Placebo
22.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Mean (Standard Error)
Unit of Measure: percent change
-3.9  (1.8) -21.2  (1.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance ≤ 0.05.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -17.3
Confidence Interval (2-Sided) 95%
-21.5 to -13
Estimation Comments Alirocumab vs Placebo
23.Secondary Outcome
Title Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
HDL-C ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.1  (1.2) 6.4  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
1.5 to 7.2
Estimation Comments Alirocumab vs Placebo
24.Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Mean (Standard Error)
Unit of Measure: percent change
1.7  (2.2) -8  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments Threshold for significance ≤ 0.05.
Method Regression, Robust
Comments Multiple imputation approach followed by robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -9.7
Confidence Interval (2-Sided) 95%
-15 to -4.4
Estimation Comments Alirocumab vs Placebo
25.Secondary Outcome
Title Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Apo A-1 ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 160 309
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.1  (1) 2.9  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alirocumab 75 mg/Up to 150 mg Q2W
Comments Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0187
Comments Threshold for significance ≤ 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
0.5 to 5.2
Estimation Comments Alirocumab vs Placebo
26.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis
Hide Description 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).
Time Frame From Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 321
Least Squares Mean (Standard Error)
Unit of Measure: percent change
9.1  (2.6) -48.1  (1.9)
27.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis
Hide Description 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.
Time Frame From Baseline to Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 322
Least Squares Mean (Standard Error)
Unit of Measure: percent change
11.5  (2.8) -40.3  (2.0)
28.Other Pre-specified Outcome
Title Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis
Hide Description 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).
Time Frame From Baseline to Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Alirocumab 75 mg/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo for alirocumab SC injection Q2W on top of stable LMT for 78 weeks.
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.
Overall Number of Participants Analyzed 163 321
Least Squares Mean (Standard Error)
Unit of Measure: percent change
14.0  (2.8) -43.7  (2.0)
Time Frame 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.
Adverse Event Reporting Description 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).
 
Arm/Group Title Placebo Alirocumab 75/Up to 150 mg Q2W
Hide Arm/Group Description Participants exposed to placebo Q2W on top of stable LMT (mean exposure of 72 weeks). Participants exposed to Alirocumab 75 mg/Up to 150 mg Q2W on top of stable LMT (mean exposure of 72 weeks).
All-Cause Mortality
Placebo Alirocumab 75/Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Alirocumab 75/Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   22/163 (13.50%)   44/322 (13.66%) 
Blood and lymphatic system disorders     
Lymphoid tissue hyperplasia  1  0/163 (0.00%)  1/322 (0.31%) 
Cardiac disorders     
Angina pectoris  1  1/163 (0.61%)  2/322 (0.62%) 
Coronary artery disease  1  0/163 (0.00%)  4/322 (1.24%) 
Acute myocardial infarction  1  1/163 (0.61%)  3/322 (0.93%) 
Cardiac failure congestive  1  1/163 (0.61%)  2/322 (0.62%) 
Ventricular extrasystoles  1  1/163 (0.61%)  0/322 (0.00%) 
Angina unstable  1  2/163 (1.23%)  2/322 (0.62%) 
Atrial fibrillation  1  2/163 (1.23%)  1/322 (0.31%) 
Bradycardia  1  0/163 (0.00%)  2/322 (0.62%) 
Atrial flutter  1  0/163 (0.00%)  1/322 (0.31%) 
Atrioventricular block  1  0/163 (0.00%)  1/322 (0.31%) 
Cardiac failure chronic  1  0/163 (0.00%)  1/322 (0.31%) 
Myocardial infarction  1  0/163 (0.00%)  1/322 (0.31%) 
Cardio-respiratory arrest  1  1/163 (0.61%)  0/322 (0.00%) 
Coronary artery occlusion  1  1/163 (0.61%)  0/322 (0.00%) 
Intracardiac thrombus  1  1/163 (0.61%)  0/322 (0.00%) 
Left ventricular dysfunction  1  1/163 (0.61%)  0/322 (0.00%) 
Mitral valve incompetence  1  1/163 (0.61%)  0/322 (0.00%) 
Ventricular fibrillation  1  1/163 (0.61%)  0/322 (0.00%) 
Eye disorders     
Cataract  1  0/163 (0.00%)  1/322 (0.31%) 
Retinal artery embolism  1  0/163 (0.00%)  1/322 (0.31%) 
Retinal degeneration  1  0/163 (0.00%)  1/322 (0.31%) 
Gastrointestinal disorders     
Gastrooesophageal reflux disease  1  0/163 (0.00%)  1/322 (0.31%) 
Colonic pseudo-obstruction  1  0/163 (0.00%)  1/322 (0.31%) 
Umbilical hernia  1  0/163 (0.00%)  1/322 (0.31%) 
Gastrointestinal haemorrhage  1  1/163 (0.61%)  0/322 (0.00%) 
Pancreatitis  1  1/163 (0.61%)  0/322 (0.00%) 
General disorders     
Non-cardiac chest pain  1  0/163 (0.00%)  1/322 (0.31%) 
Pyrexia  1  1/163 (0.61%)  0/322 (0.00%) 
Gait disturbance  1  1/163 (0.61%)  0/322 (0.00%) 
Hepatobiliary disorders     
Hepatitis alcoholic  1  0/163 (0.00%)  1/322 (0.31%) 
Bile duct stone  1  1/163 (0.61%)  0/322 (0.00%) 
Cholecystitis acute  1  1/163 (0.61%)  0/322 (0.00%) 
Infections and infestations     
Influenza  1  1/163 (0.61%)  0/322 (0.00%) 
Pneumonia  1  0/163 (0.00%)  1/322 (0.31%) 
Cellulitis  1  1/163 (0.61%)  0/322 (0.00%) 
Pilonidal cyst  1  0/163 (0.00%)  1/322 (0.31%) 
Pyelonephritis  1  0/163 (0.00%)  1/322 (0.31%) 
Septic shock  1  0/163 (0.00%)  1/322 (0.31%) 
Clostridium difficile colitis  1  1/163 (0.61%)  0/322 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  1/163 (0.61%)  0/322 (0.00%) 
Post lumbar puncture syndrome  1  0/163 (0.00%)  1/322 (0.31%) 
Radius fracture  1  0/163 (0.00%)  1/322 (0.31%) 
Thoracic vertebral fracture  1  0/163 (0.00%)  1/322 (0.31%) 
Toxicity to various agents  1  0/163 (0.00%)  1/322 (0.31%) 
Spinal compression fracture  1  1/163 (0.61%)  0/322 (0.00%) 
Investigations     
Hepatic enzyme increased  1  0/163 (0.00%)  1/322 (0.31%) 
International normalised ratio increased  1  0/163 (0.00%)  1/322 (0.31%) 
Metabolism and nutrition disorders     
Fluid retention  1  1/163 (0.61%)  0/322 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  0/163 (0.00%)  1/322 (0.31%) 
Osteoarthritis  1  0/163 (0.00%)  3/322 (0.93%) 
Bursitis  1  0/163 (0.00%)  1/322 (0.31%) 
Tendonitis  1  1/163 (0.61%)  0/322 (0.00%) 
Arthritis  1  0/163 (0.00%)  1/322 (0.31%) 
Lumbar spinal stenosis  1  0/163 (0.00%)  1/322 (0.31%) 
Musculoskeletal chest pain  1  1/163 (0.61%)  1/322 (0.31%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acinic cell carcinoma of salivary gland  1  0/163 (0.00%)  1/322 (0.31%) 
Bladder transitional cell carcinoma  1  0/163 (0.00%)  1/322 (0.31%) 
Lung neoplasm  1  0/163 (0.00%)  1/322 (0.31%) 
Non-small cell lung cancer metastatic  1  0/163 (0.00%)  1/322 (0.31%) 
Pancreatic carcinoma metastatic  1  0/163 (0.00%)  1/322 (0.31%) 
Prostate cancer recurrent  1  0/163 (0.00%)  1/322 (0.31%) 
Renal cancer metastatic  1  0/163 (0.00%)  1/322 (0.31%) 
Thyroid adenoma  1  0/163 (0.00%)  1/322 (0.31%) 
Benign neoplasm of thyroid gland  1  1/163 (0.61%)  0/322 (0.00%) 
Breast cancer  1  1/163 (0.61%)  0/322 (0.00%) 
Prostate cancer  1  1/163 (0.61%)  0/322 (0.00%) 
Nervous system disorders     
Presyncope  1  0/163 (0.00%)  1/322 (0.31%) 
Syncope  1  1/163 (0.61%)  2/322 (0.62%) 
Carotid artery stenosis  1  1/163 (0.61%)  0/322 (0.00%) 
Cerebrovascular accident  1  0/163 (0.00%)  1/322 (0.31%) 
Transient ischaemic attack  1  1/163 (0.61%)  0/322 (0.00%) 
Psychiatric disorders     
Depression  1  0/163 (0.00%)  1/322 (0.31%) 
Renal and urinary disorders     
Urinary bladder polyp  1  0/163 (0.00%)  1/322 (0.31%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  0/163 (0.00%)  1/322 (0.31%) 
Asthma  1  1/163 (0.61%)  0/322 (0.00%) 
Chronic obstructive pulmonary disease  1  1/163 (0.61%)  0/322 (0.00%) 
Hyperventilation  1  1/163 (0.61%)  0/322 (0.00%) 
Skin and subcutaneous tissue disorders     
Eczema nummular  1  0/163 (0.00%)  1/322 (0.31%) 
Social circumstances     
Pregnancy of partner  1  0/163 (0.00%)  1/322 (0.31%) 
Miscarriage of partner  1  0/163 (0.00%)  2/322 (0.62%) 
Vascular disorders     
Arteriovenous fistula  1  0/163 (0.00%)  1/322 (0.31%) 
Trousseau's syndrome  1  0/163 (0.00%)  1/322 (0.31%) 
Aortic stenosis  1  1/163 (0.61%)  0/322 (0.00%) 
Hypertensive crisis  1  1/163 (0.61%)  0/322 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Alirocumab 75/Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   70/163 (42.94%)   142/322 (44.10%) 
General disorders     
Injection site reaction  1  18/163 (11.04%)  40/322 (12.42%) 
Infections and infestations     
Nasopharyngitis  1  12/163 (7.36%)  36/322 (11.18%) 
Upper respiratory tract infection  1  14/163 (8.59%)  22/322 (6.83%) 
Influenza  1  9/163 (5.52%)  20/322 (6.21%) 
Sinusitis  1  7/163 (4.29%)  17/322 (5.28%) 
Bronchitis  1  9/163 (5.52%)  10/322 (3.11%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/163 (5.52%)  20/322 (6.21%) 
Back pain  1  7/163 (4.29%)  18/322 (5.59%) 
Myalgia  1  11/163 (6.75%)  6/322 (1.86%) 
Nervous system disorders     
Headache  1  9/163 (5.52%)  15/322 (4.66%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report form (eCRF).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01623115     History of Changes
Other Study ID Numbers: EFC12492
U1111-1121-4275 ( Other Identifier: UTN )
2011-005109-56 ( EudraCT Number )
First Submitted: June 15, 2012
First Posted: June 19, 2012
Results First Submitted: August 20, 2015
Results First Posted: November 4, 2015
Last Update Posted: February 8, 2016