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Trial record 1 of 1 for:    EFC14074 | Studies With Results | Phase 3
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Evaluation of Alirocumab in Addition to Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia in South Korea and Taiwan

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ClinicalTrials.gov Identifier: NCT02289963
Recruitment Status : Completed
First Posted : November 13, 2014
Results First Posted : June 26, 2017
Last Update Posted : June 26, 2017
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: Placebo (for Alirocumab)
Drug: Alirocumab
Drug: Lipid-Modifying Therapy (LMT)
Enrollment 199
Recruitment Details The study was conducted at 27 centers in South Korea and Taiwan. Overall 316 participants were screened between January and September 2015, of whom 117 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke, intensity of statin treatment and country. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1 ratio (Placebo:Alirocumab). A total of 199 participants were randomized.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W 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 102 [1] 97 [1]
Treated 102 97
Completed 97 87
Not Completed 5 10
Reason Not Completed
Adverse Event             1             2
Poor compliance to protocol             1             0
Withdrawal by Subject             1             0
Last injection missed             2             2
End treatment visit outside visit window             0             4
Other than specified above             0             2
[1]
Randomized
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W Total
Hide Arm/Group Description Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks. Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W 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 102 97 199
Hide Baseline Analysis Population Description
Baseline population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 102 participants 97 participants 199 participants
60.1  (9.1) 61.2  (10.4) 60.6  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 102 participants 97 participants 199 participants
Female
21
  20.6%
14
  14.4%
35
  17.6%
Male
81
  79.4%
83
  85.6%
164
  82.4%
Calculated LDL-C in mmol/L   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 102 participants 97 participants 199 participants
2.572  (0.653) 2.513  (0.721) 2.543  (0.686)
[1]
Measure Description: Calculated LDL-C in mmol/L from Friedewald formula (LDL-C = Total cholesterol - High-density lipoprotein cholesterol [HDL-C] - [Triglyceride/2.2]).
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 up to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population that included all randomized participants with one baseline and at least one post-baseline calculated LDL-C on- or off-treatment.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Error)
Unit of Measure: percent change
6.3  (2.9) -57.1  (3.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Comments Alirocumab group was compared to placebo group using an appropriate contrast statement.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean Difference
Estimated Value -63.4
Confidence Interval (2-Sided) 95%
-71.6 to -55.2
Estimation Comments Alirocumab 75 mg Q2W/ Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT (mITT) population that included all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 97
Least Squares Mean (Standard Error)
Unit of Measure: Percent Change
6.0  (2.7) -60.2  (2.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance was at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -66.2
Confidence Interval (2-Sided) 95%
-73.9 to -58.4
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.7  (2.2) -57.9  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -62.5
Confidence Interval (2-Sided) 95%
-68.8 to -56.3
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 97
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.7  (2.2) -58.4  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -63.1
Confidence Interval (2-Sided) 95%
-69.2 to -57.0
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
5.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
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 Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 96
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.1  (2.3) -42.3  (2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -46.3
Confidence Interval (2-Sided) 95%
-53.0 to -39.7
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).
Time Frame From Baseline to Week 24
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 Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 99 95
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.8  (2.1) -45.4  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -49.2
Confidence Interval (2-Sided) 95%
-55.3 to -43.1
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
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 Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Error)
Unit of Measure: percent change
4.3  (2.4) -47.2  (2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -51.5
Confidence Interval (2-Sided) 95%
-58.4 to -44.6
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 97
Least Squares Mean (Standard Deviation)
Unit of Measure: percent change
4.1  (2.2) -50.1  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -54.2
Confidence Interval (2-Sided) 95%
-60.6 to -47.8
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
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 Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Deviation)
Unit of Measure: percent change
4.0  (1.8) -31.2  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.2
Confidence Interval (2-Sided) 95%
-40.3 to -30.1
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Apo B ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 96
Least Squares Mean (Standard Error)
Unit of Measure: percent change
5.2  (1.8) -40.9  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -46.1
Confidence Interval (2-Sided) 95%
-51.2 to -41.0
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Non-HDL-C ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Deviation)
Unit of Measure: percent change
3.9  (1.8) -47.3  (1.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -51.2
Confidence Interval (2-Sided) 95%
-56.4 to -46.1
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Total-C ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.8  (1.4) -32.9  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.8
Confidence Interval (2-Sided) 95%
-39.7 to -31.9
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
13.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Hide Description Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data up to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Measure Type: Number
Unit of Measure: percentage of participants
14.2 85.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 46.9
Confidence Interval (2-Sided) 95%
18.4 to 119.4
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
14.Secondary Outcome
Title Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis
Hide Description Adjusted percentages at Week 24 were obtained from multiple imputation approach model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 97
Measure Type: Number
Unit of Measure: percentage of participants
14.1 88.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Regression, Logistic
Comments Multiple imputation approach followed by logistic regression model
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 70.0
Confidence Interval (2-Sided) 95%
23.3 to 210.8
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
15.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 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data up to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Mean (Standard Error)
Unit of Measure: percent change
-2.251  (2.962) -35.862  (3.011)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Threshold for significance at 0.05 level.
Method Regression, Robust
Comments Multiple imputation approach followed by a robust regression model.
Method of Estimation Estimation Parameter Adjusted Mean Difference
Estimated Value -33.611
Confidence Interval (2-Sided) 95%
-41.883 to -25.338
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
16.Secondary Outcome
Title Percent Change From Baseline in High Density Lipoprotein (HDL-C) at Week 24 - ITT Analysis
Hide Description Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
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 Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Error)
Unit of Measure: percent change
6.2  (1.7) 13.8  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
2.6 to 12.4
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
17.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 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Mean (Standard Error)
Unit of Measure: percent change
-3.627  (3.111) -8.143  (3.204)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Alirocumab 75 mg Q2W/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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3110
Comments Threshold for significance at 0.05 level.
Method Regression, Robust
Comments Multiple imputation approach followed by a robust regression model.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.515
Confidence Interval (2-Sided) 95%
-13.250 to 4.219
Estimation Comments Alirocumab 75 mg Q2W/Up to 150 mg Q2W vs. Placebo Q2W
18.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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
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 Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 96
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.2  (1.2) 4.5  (1.2)
19.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 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Mean (Standard Error)
Unit of Measure: percent change
-1.676  (2.732) -33.601  (2.778)
20.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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HDL-C ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.0  (1.5) 7.1  (1.6)
21.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 were obtained from multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 102 97
Mean (Standard Error)
Unit of Measure: percent change
2.113  (3.192) -6.999  (3.252)
22.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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Apo A-1 ITT population.
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description:
Placebo (for alirocumab) SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Overall Number of Participants Analyzed 100 96
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.5  (1.1) 4.5  (1.1)
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 32 post-treatment follow-up visit) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘treatment emergent period’ (the time from the first dose of study drug up to the last dose of study drug +70 days).
 
Arm/Group Title Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Hide Arm/Group Description Participants exposed to Placebo (for Alirocumab) SC injection Q2W added to stable LMT (mean exposure of 23 weeks). Participants exposed to Alirocumab 75 mg Q2W/up to 150 mg Q2W SC injection added to stable LMT (mean exposure of 24 weeks).
All-Cause Mortality
Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   0/102 (0.00%)   1/97 (1.03%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   10/102 (9.80%)   17/97 (17.53%) 
Cardiac disorders     
Angina pectoris  1  0/102 (0.00%)  2/97 (2.06%) 
Coronary artery disease  1  1/102 (0.98%)  2/97 (2.06%) 
Angina unstable  1  1/102 (0.98%)  1/97 (1.03%) 
Supraventricular tachycardia  1  0/102 (0.00%)  1/97 (1.03%) 
Acute myocardial infarction  1  1/102 (0.98%)  0/97 (0.00%) 
Coronary artery stenosis  1  1/102 (0.98%)  0/97 (0.00%) 
Infections and infestations     
Influenza  1  0/102 (0.00%)  1/97 (1.03%) 
Diarrhoea infectious  1  1/102 (0.98%)  0/97 (0.00%) 
Pulmonary tuberculosis  1  1/102 (0.98%)  0/97 (0.00%) 
Injury, poisoning and procedural complications     
Ligament sprain  1  0/102 (0.00%)  1/97 (1.03%) 
Loss of anatomical alignment after fracture reduction  1  0/102 (0.00%)  1/97 (1.03%) 
Muscle strain  1  0/102 (0.00%)  1/97 (1.03%) 
Patella fracture  1  0/102 (0.00%)  1/97 (1.03%) 
Post procedural haematoma  1  0/102 (0.00%)  1/97 (1.03%) 
Radius fracture  1  0/102 (0.00%)  1/97 (1.03%) 
Road traffic accident  1  1/102 (0.98%)  0/97 (0.00%) 
Traumatic fracture  1  0/102 (0.00%)  1/97 (1.03%) 
Arterial injury  1  1/102 (0.98%)  0/97 (0.00%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  0/102 (0.00%)  1/97 (1.03%) 
Myopathy  1  0/102 (0.00%)  1/97 (1.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign neoplasm of spinal cord  1  0/102 (0.00%)  1/97 (1.03%) 
Rectal adenocarcinoma  1  0/102 (0.00%)  1/97 (1.03%) 
Nervous system disorders     
Cerebellar haemorrhage  1  0/102 (0.00%)  1/97 (1.03%) 
Cervical myelopathy  1  0/102 (0.00%)  1/97 (1.03%) 
Ischaemic stroke  1  1/102 (0.98%)  1/97 (1.03%) 
Neuromuscular pain  1  1/102 (0.98%)  0/97 (0.00%) 
Product Issues     
Device failure  1  0/102 (0.00%)  1/97 (1.03%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  1/102 (0.98%)  0/97 (0.00%) 
Vascular disorders     
Brachiocephalic artery stenosis  1  0/102 (0.00%)  1/97 (1.03%) 
Peripheral arterial occlusive disease  1  1/102 (0.98%)  0/97 (0.00%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Q2W Alirocumab 75 mg Q2W/Up to 150 mg Q2W
Affected / at Risk (%) Affected / at Risk (%)
Total   15/102 (14.71%)   19/97 (19.59%) 
Gastrointestinal disorders     
Diarrhoea  1  1/102 (0.98%)  5/97 (5.15%) 
Infections and infestations     
Nasopharyngitis  1  4/102 (3.92%)  6/97 (6.19%) 
Upper respiratory tract infection  1  6/102 (5.88%)  3/97 (3.09%) 
Nervous system disorders     
Dizziness  1  3/102 (2.94%)  6/97 (6.19%) 
Headache  1  3/102 (2.94%)  5/97 (5.15%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
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: NCT02289963     History of Changes
Other Study ID Numbers: EFC14074
U1111-1157-3294 ( Other Identifier: UTN )
First Submitted: November 10, 2014
First Posted: November 13, 2014
Results First Submitted: April 24, 2017
Results First Posted: June 26, 2017
Last Update Posted: June 26, 2017