Hypercholesterolemia
Conditions
Brief summary
Primary Objective: To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by a regimen of Alirocumab including a starting dose of 150 mg every 4 weeks (Q4W) as add-on to non-statin lipid modifying background therapy or as monotherapy in comparison with placebo in participants with primary hypercholesterolemia not treated with a statin. Secondary Objective: * To evaluate the effects on other lipid parameters of Alirocumab 150 mg Q4W versus placebo. * To evaluate the safety and tolerability of Alirocumab 150 mg Q4W. Alirocumab 75 mg Q2W was added as a calibrator arm.
Detailed description
The core study duration was approximately 35 weeks per participant (screening: 3 weeks, double-blind treatment period: 24 weeks; follow-up: 8 weeks). Participants who successfully completed the treatment period had the possibility to participate in an optional open-label treatment period with Alirocumab 150 mg Q4W until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first.
Interventions
DRUGAlirocumab
Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).
Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).
DRUGNon-statin LMT
Ezetimibe or Fenofibrate at stable dose as background therapy.
OTHERDiet Alone
Stable cholesterol-lowering diet as background therapy.
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Masking during the double-blind treatment period
Intervention model description
A double-blind treatment period of 24 weeks (3 parallel arms) followed by an open-label extension period (single arm)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants with primary hypercholesterolemia (heterozygous familial hypercholesterolemia \[heFH\] or non-FH) not adequately controlled with their non-statin LMT (either ezetimibe or fenofibrate) or diet alone.
Exclusion criteria
* LDL-C \<70 mg/dL (1.81 mmol/L) at screening for statin intolerant participants at very high cardiovascular (CV) risk; * LDL-C \<100 mg/dL (\<2.59 mmol/L) at screening for statin intolerant participants at high or moderate CV risk or, participants not fulfilling the statin intolerant definition at moderate CV risk; * LDL-C ≥160 mg/dL (≥4.1 mmol/L) at screening for participants receiving diet only or, participants not fulfilling the statin intolerant definition at moderate CV risk and receiving a non-statin LMT. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) | From Baseline to Week 24 | 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 24 regardless of status on- or off-treatment were used in the model (ITT analysis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). |
| Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). |
| Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points. |
| Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points. |
| Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). |
| Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). |
| Percent Change From Baseline in Total-C at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis | From Baseline to Week 24 | Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and \<5%. High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia. Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion \>50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included. |
| Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis | From Baseline to Week 24 | Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). |
| Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
| Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis | From Baseline to Week 24 | Adjusted percentages at Week 24 from LOCF approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). |
| Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. |
| Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
| Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | From Baseline to Week 24 | Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168 | Mean percent changes (and standard deviations) observed during the open-label extension period are provided. |
Countries
Australia, Belgium, Canada, Denmark, Netherlands, New Zealand, Spain, United States
Participant flow
Recruitment details
The study was conducted at 43 centers in 8 countries. A total of 402 participants were screened between December-2013 and May-2014, of whom 233 were randomized for double-blind (DB) treatment period and 169 were screen failures. Out of 233 randomized for DB period, 205 participants entered the optional open-label (OL) extension period.
Pre-assignment details
Randomization was stratified by statin intolerant status & background therapy (non-statin lipid therapy vs diet). Randomization followed a 1:2:1 ratio for placebo, Alirocumab 75 mg and Alirocumab 150 mg instead of 1:1:2 as initially planned due to systematic error in treatment allocation algorithm discovered after all participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Q2W Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.
Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. | 58 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline.
Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. | 116 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W Period 1: Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline.
Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. | 59 |
| Total | 233 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension Open Label Treatment | Adverse Event | 1 | 7 | 3 |
| Extension Open Label Treatment | Other than specified above | 2 | 7 | 2 |
| Extension Open Label Treatment | Participant moved | 1 | 2 | 0 |
| Extension Open Label Treatment | Poor compliance to protocol | 1 | 1 | 0 |
| Period 1: 24-Week Double-blind Treatment | Adverse Event | 2 | 2 | 5 |
| Period 1: 24-Week Double-blind Treatment | Consent withdrawn by participant | 1 | 0 | 1 |
| Period 1: 24-Week Double-blind Treatment | Other than specified above | 1 | 3 | 1 |
| Period 1: 24-Week Double-blind Treatment | Physician Decision | 0 | 1 | 0 |
| Period 1: 24-Week Double-blind Treatment | Poor compliance to protocol | 0 | 2 | 1 |
| Period 1: 24-Week Double-blind Treatment | Randomized but not treated | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Placebo Q2W | Total |
|---|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 9.9 | 64.2 years STANDARD_DEVIATION 10 | 63.1 years STANDARD_DEVIATION 10.7 | 63.1 years STANDARD_DEVIATION 10.1 |
| Calculated LDL-C in mg/dL | 154.5 mg/dL STANDARD_DEVIATION 44.6 | 163.9 mg/dL STANDARD_DEVIATION 69.1 | 158.5 mg/dL STANDARD_DEVIATION 47.3 | 157.9 mg/dL STANDARD_DEVIATION 52.4 |
| Calculated LDL-C in mmol/L | 4.002 mmol/L STANDARD_DEVIATION 1.154 | 4.245 mmol/L STANDARD_DEVIATION 1.789 | 4.106 mmol/L STANDARD_DEVIATION 1.226 | 4.089 mmol/L STANDARD_DEVIATION 1.356 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 1 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 54 Participants | 57 Participants | 220 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 108 Participants | 55 Participants | 56 Participants | 219 Participants |
| Sex: Female, Male Female | 47 Participants | 29 Participants | 27 Participants | 103 Participants |
| Sex: Female, Male Male | 69 Participants | 30 Participants | 31 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 115 | 0 / 58 | 0 / 51 | 2 / 106 | 1 / 48 |
| other Total, other adverse events | 28 / 58 | 61 / 115 | 29 / 58 | 42 / 51 | 71 / 106 | 31 / 48 |
| serious Total, serious adverse events | 4 / 58 | 7 / 115 | 7 / 58 | 15 / 51 | 28 / 106 | 14 / 48 |
Outcome results
Primary
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)
Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time frame: From Baseline to Week 24
Population: ITT population that included all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) | 4.7 percent change | Standard Error 2.3 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) | -53.5 percent change | Standard Error 1.6 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) | -51.7 percent change | Standard Error 2.3 |
Comparison: Alirocumab 150 mg Q4W/up to 150 mg Q2W was compared to placebo group using an appropriate contrast statement.p-value: <0.000195% CI: [-62.9, -49.9]Mixed Models Analysis
Secondary
Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis
Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis | 0.0 percentage of participants |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis | 60.0 percentage of participants |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis | 50.0 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [20, 9999]Regression, Logistic
Secondary
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis
Adjusted percentages at Week 24 from LOCF approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis | 0.0 percentage of participants |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis | 61.7 percentage of participants |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis | 50.9 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [22.2, 9999]Regression, Logistic
Secondary
Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and \<5%. High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia. Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion \>50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis | 1.8 percentage of participants |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis | 70.3 percentage of participants |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis | 63.9 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [29.1, 2690.1]Regression, Logistic
Secondary
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis | 1.8 percentage of participants |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis | 72.7 percentage of participants |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis | 67.7 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [36.2, 3479.5]Regression, Logistic
Secondary
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 2.6 percent change | Standard Error 1.5 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 5.9 percent change | Standard Error 1.1 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis | 7.6 percent change | Standard Error 1.5 |
Secondary
Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 3.4 percent change | Standard Error 1.5 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 8.2 percent change | Standard Error 1.1 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis | 10.0 percent change | Standard Error 1.5 |
Secondary
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | 7.0 percent change | Standard Error 2.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -38.4 percent change | Standard Error 1.6 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Apo B at Week 12 - ITT Analysis | -31.3 percent change | Standard Error 2.2 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-44.3, -32.1]Mixed Models Analysis
Secondary
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 24
Population: mITT population. Number of participants analyzed = participants of the mITT population with available data at specified time-points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis | 7.7 percent change | Standard Error 2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis | -41.2 percent change | Standard Error 1.4 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis | -40.9 percent change | Standard Error 2.1 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-54.3, -42.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | 7.5 percent change | Standard Error 2.1 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -39.7 percent change | Standard Error 1.5 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis | -38.9 percent change | Standard Error 2.2 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-52.4, -40.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis | 3.6 percent change | Standard Error 1.9 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis | -54.1 percent change | Standard Error 1.3 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis | -55.0 percent change | Standard Error 1.9 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-63.8, -53.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | 3.2 percent change | Standard Error 2.5 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -50.8 percent change | Standard Error 1.7 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis | -41.7 percent change | Standard Error 2.4 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-51.8, -38.1]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | 3.6 percent change | Standard Error 2.3 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -51.5 percent change | Standard Error 1.6 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -44.8 percent change | Standard Error 2.3 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-54.8, -41.9]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).
Time frame: From Baseline to Week 24
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | 5.1 percent change | Standard Error 2.1 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -55.3 percent change | Standard Error 1.5 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis | -54.6 percent change | Standard Error 2.1 |
Comparison: 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.p-value: <0.000195% CI: [-65.6, -53.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis | 3.2 percent change | Standard Error 2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis | -53.6 percent change | Standard Error 1.4 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis | -52.3 percent change | Standard Error 2 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-61.1, -49.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | 2.1 percent change | Standard Error 3.9 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -11.3 percent change | Standard Error 2.7 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis | -3.0 percent change | Standard Error 3.8 |
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | 1.1 percent change | Standard Error 3.8 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -10.6 percent change | Standard Error 2.7 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis | -9.2 percent change | Standard Error 3.9 |
Secondary
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | -0.8 percent change | Standard Error 1.9 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 6.8 percent change | Standard Error 1.3 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis | 8.6 percent change | Standard Error 1.9 |
Secondary
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | -2.4 percent change | Standard Error 1.9 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 7.4 percent change | Standard Error 1.4 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis | 7.7 percent change | Standard Error 2 |
Secondary
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | 2.2 percent change | Standard Error 3.4 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -16.5 percent change | Standard Error 2.4 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis | -5.7 percent change | Standard Error 3.3 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.089295% CI: [-17.1, 1.2]Regression, Robust
Secondary
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis | 4.1 percent change | Standard Error 3.7 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis | -21.8 percent change | Standard Error 2.6 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis | -15.5 percent change | Standard Error 3.7 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.000295% CI: [-29.8, -9.4]Regression, Robust
Secondary
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | 3.0 percent change | Standard Error 2.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -43.4 percent change | Standard Error 1.5 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis | -34.9 percent change | Standard Error 2.2 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-43.9, -31.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis | 4.8 percent change | Standard Error 2.1 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis | -45.3 percent change | Standard Error 1.5 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis | -44.2 percent change | Standard Error 2.1 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-54.9, -43.2]Mixed Models Analysis
Secondary
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 24
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis | 5.0 percent change | Standard Error 1.9 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis | -46.9 percent change | Standard Error 1.3 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis | -46.7 percent change | Standard Error 1.9 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-57.1, -46.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | 1.8 percent change | Standard Error 1.6 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -32.6 percent change | Standard Error 1.2 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Total-C at Week 12 - ITT Analysis | -24.5 percent change | Standard Error 1.6 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-30.9, -21.7]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Time frame: From Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Total-C at Week 24 - ITT Analysis | 3.0 percent change | Standard Error 1.6 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Total-C at Week 24 - ITT Analysis | -34.0 percent change | Standard Error 1.1 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Total-C at Week 24 - ITT Analysis | -32.3 percent change | Standard Error 1.6 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-39.8, -30.8]Mixed Models Analysis
Other Pre-specified
Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase
Mean percent changes (and standard deviations) observed during the open-label extension period are provided.
Time frame: Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168
Population: Open-label extension population included all participants who received at least one dose or part of dose of Alirocumab during the open label extension period. Here, number analyzed signifies the number of participants evaluable for each specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 72 | -50.8 percent change | Standard Deviation 20.6 |
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 36 | -36.1 percent change | Standard Deviation 22 |
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 96 | -49.8 percent change | Standard Deviation 20.4 |
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 168 | -47.8 percent change | Standard Deviation 24.2 |
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 48 | -46.5 percent change | Standard Deviation 24.2 |
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 120 | -50.6 percent change | Standard Deviation 20.9 |
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 32 | -37.3 percent change | Standard Deviation 18.8 |
| Placebo Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 144 | -52.7 percent change | Standard Deviation 17.6 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 48 | -49.2 percent change | Standard Deviation 18.7 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 144 | -48.7 percent change | Standard Deviation 23.7 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 32 | -41.1 percent change | Standard Deviation 21.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 168 | -66.2 percent change | Standard Deviation 17.1 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 36 | -39.2 percent change | Standard Deviation 21.2 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 72 | -53.7 percent change | Standard Deviation 19.5 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 96 | -52.8 percent change | Standard Deviation 19.6 |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 120 | -53.7 percent change | Standard Deviation 18.7 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 36 | -43.1 percent change | Standard Deviation 13.7 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 32 | -46.9 percent change | Standard Deviation 13.3 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 48 | -48.7 percent change | Standard Deviation 21.7 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 72 | -52.3 percent change | Standard Deviation 21.3 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 96 | -46.8 percent change | Standard Deviation 22 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 120 | -51.8 percent change | Standard Deviation 24.1 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 144 | -49.4 percent change | Standard Deviation 20.9 |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase | Week 168 | -60.0 percent change | Standard Deviation 4.6 |