Hypercholesterolemia
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)
Interventions
DRUGAlirocumab
Alirocumab two SC injections in the abdomen only.
DRUGPlacebo
Placebo two SC injections in the abdomen only.
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Must meet the World Health Organization criteria for heFH 2. Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening 3. Serum LDL-C levels ≥ 100 mg/dL at screening 4. Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit 5. A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential Key
Exclusion criteria
1. Participants with homozygous FH (clinically or by previous genotyping) 2. Use of a medication (other than a statin or EZE) to alter serum lipids within 42 days (6 weeks) before screening including, but not limited to: * Fibrates * Niacin (\>500 mg/day) * Omega-3 fatty acids (\>1000 mg/day of DHA/EPA) * Bile acid resins 3. Use of nutraceuticals or OTC medications that may alter lipid levels that are not stable for at least 6 weeks before screening and are not planned to remain constant throughout the study. Examples include: * Omega-3 fatty acids (≤1000 mg/day of DHA/EPA) * Niacin (≤500 mg/day) * Plant stanols, such as found in Benecol, flax seed oil, psyllium * Red yeast rice 4. Disorders known to influence lipid levels, such as nephrotic syndrome, significant liver disease, Cushing's disease, untreated hypothyroidism (patients on stable thyroid replacement for at least 12 weeks before the full screening visit, who are metabolically euthyroid by thyroid-stimulating hormone (TSH) testing are allowed) 5. Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit) 6. Fasting serum TG \>350 mg/dL screening 7. LDL apheresis within 12 months before screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis | Week 12 (LOCF) | Calculated LDL-C value was obtained from Friedewald formula. |
| Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis | Week 12 (LOCF) | Calculated LDL-C value was obtained from Friedewald formula. |
| Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.. |
| Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range) |
| Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range) |
| Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Calculated LDL-C value was obtained from Friedewald formula. Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis | From Baseline to Week 12 | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis | From Baseline to Week 12 | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range) |
| Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | From Baseline to Week 12 (LOCF) | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range) |
| Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | From Baseline to Week 12 | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
Countries
Canada, United States
Participant flow
Recruitment details
The study was conducted at 16 centers in the United States of America and Canada. Overall, 118 participants were screened between January 2011 and June 2011.
Pre-assignment details
Randomization was stratified by concomitant use of ezetimibe (Yes/No). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1:1:1 ratio after confirmation of selection criteria. 77 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | 15 |
| Alirocumab 150 mg Q4W Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | 15 |
| Alirocumab 200 mg Q4W Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | 16 |
| Alirocumab 300 mg Q4W Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | 15 |
| Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | 16 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Alirocumab 150 mg Q4W | Alirocumab 200 mg Q4W | Alirocumab 300 mg Q4W | Alirocumab 150 mg Q2W | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 9.6 | 51.3 years STANDARD_DEVIATION 7.7 | 52.9 years STANDARD_DEVIATION 11.2 | 54.3 years STANDARD_DEVIATION 9.6 | 56.3 years STANDARD_DEVIATION 10.2 | 53.4 years STANDARD_DEVIATION 9.7 |
| Low Density Lipoprotein Cholesterol (LDL-C) in mg/dL | 150.8 mg/dL STANDARD_DEVIATION 34 | 166.7 mg/dL STANDARD_DEVIATION 50.1 | 169.8 mg/dL STANDARD_DEVIATION 57 | 139.6 mg/dL STANDARD_DEVIATION 24.7 | 147.2 mg/dL STANDARD_DEVIATION 32.6 | 154.9 mg/dL STANDARD_DEVIATION 42.1 |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 7 Participants | 8 Participants | 3 Participants | 30 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 9 Participants | 7 Participants | 13 Participants | 47 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 15 | 12 / 15 | 13 / 16 | 13 / 15 | 12 / 16 |
| serious Total, serious adverse events | 1 / 15 | 0 / 15 | 0 / 16 | 0 / 15 | 0 / 16 |
Outcome results
Primary
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.
Time frame: From Baseline to Week 12 (LOCF)
Population: Modified Intent-To-Treat (mITT) population included all randomized participants with one baseline and at least one post baseline on-treatment calculated LDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -10.7 percent change | Standard Error 5 |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -28.9 percent change | Standard Error 5.1 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -31.5 percent change | Standard Error 4.9 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -42.5 percent change | Standard Error 5.1 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -67.9 percent change | Standard Error 4.9 |
Comparison: Each treatment group was compared to placebo using ANCOVA-derived contrasts.~A hierarchical testing procedure was applied to ensure strong control of overall Type-I error rate at 0.05 level. Order was following:~1. Alirocumab 150 mg Q2W versus placebo~2. Alirocumab 300 mg Q4W versus placebo~3. Alirocumab 200 mg Q4W versus placebo~4. Alirocumab 150 mg Q4W versus placebo~Testing continued only when high-order test was statistically significant at 5% level.p-value: 0ANCOVA
p-value: 0ANCOVA
p-value: 0.0035ANCOVA
p-value: 0.0113ANCOVA
Secondary
Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-A1 value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis | -9.7 mg/dL | Standard Error 4.6 |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis | 3.4 mg/dL | Standard Error 4.5 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis | 2.8 mg/dL | Standard Error 4.3 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis | 7.8 mg/dL | Standard Error 4.6 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis | 11.0 mg/dL | Standard Error 4.4 |
Secondary
Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-B value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis | -9.3 mg/dL | Standard Error 5.5 |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis | -24.3 mg/dL | Standard Error 5.5 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis | -28.7 mg/dL | Standard Error 5.3 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis | -34.7 mg/dL | Standard Error 5.6 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis | -64.4 mg/dL | Standard Error 5.3 |
Secondary
Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
Calculated LDL-C value was obtained from Friedewald formula. Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one on-treatment calculated LDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -19.1 mg/dL | Standard Error 7.9 |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -42.2 mg/dL | Standard Error 8 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -51.3 mg/dL | Standard Error 7.7 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -66.9 mg/dL | Standard Error 8 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | -102.5 mg/dL | Standard Error 7.6 |
Secondary
Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline HDL-C value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis | 0.4 mg/dL | Standard Error 1.9 |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis | 4.2 mg/dL | Standard Error 1.9 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis | 3.3 mg/dL | Standard Error 1.8 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis | 4.5 mg/dL | Standard Error 2 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis | 6.0 mg/dL | Standard Error 1.8 |
Secondary
Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment lipoprotein(a) value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -2.0 mg/dL |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -1.5 mg/dL |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -1.8 mg/dL |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -8.0 mg/dL |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -11.5 mg/dL |
Secondary
Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment non-HDL-C value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -22.8 mg/dL | Standard Error 8.8 |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -46.0 mg/dL | Standard Error 8.9 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -52.3 mg/dL | Standard Error 8.6 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -70.6 mg/dL | Standard Error 9 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -103.6 mg/dL | Standard Error 8.5 |
Secondary
Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment total cholesterol value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -20.3 mg/dL | Standard Error 9.4 |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -40.3 mg/dL | Standard Error 9.5 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -50.1 mg/dL | Standard Error 9.2 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -61.7 mg/dL | Standard Error 9.5 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -99.9 mg/dL | Standard Error 9.1 |
Secondary
Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range)
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment fasting triglycerides value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis | -11.0 mg/dL |
| Alirocumab 150 mg Q4W | Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis | -20.0 mg/dL |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis | -13.5 mg/dL |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis | -3.5 mg/dL |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis | -14.8 mg/dL |
Secondary
Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-B and ApoA-1 value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis | -0.03 ratio | Standard Error 0.04 |
| Alirocumab 150 mg Q4W | Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis | -0.18 ratio | Standard Error 0.04 |
| Alirocumab 200 mg Q4W | Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis | -0.20 ratio | Standard Error 0.04 |
| Alirocumab 300 mg Q4W | Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis | -0.25 ratio | Standard Error 0.04 |
| Alirocumab 150 mg Q2W | Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis | -0.49 ratio | Standard Error 0.04 |
Secondary
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis
Calculated LDL-C value was obtained from Friedewald formula.
Time frame: Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one on-treatment calculated LDL-C.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis | 13.3 percentage of participants |
| Alirocumab 150 mg Q4W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis | 26.7 percentage of participants |
| Alirocumab 200 mg Q4W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis | 18.8 percentage of participants |
| Alirocumab 300 mg Q4W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis | 66.7 percentage of participants |
| Alirocumab 150 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis | 93.8 percentage of participants |
Secondary
Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis
Calculated LDL-C value was obtained from Friedewald formula.
Time frame: Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one on-treatment calculated LDL-C.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis | 0.0 percentage of participants |
| Alirocumab 150 mg Q4W | Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis | 13.3 percentage of participants |
| Alirocumab 200 mg Q4W | Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis | 12.5 percentage of participants |
| Alirocumab 300 mg Q4W | Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis | 46.7 percentage of participants |
| Alirocumab 150 mg Q2W | Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis | 81.3 percentage of participants |
Secondary
Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-A1 value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis | -5.3 percent change | Standard Error 3.1 |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis | 2.4 percent change | Standard Error 3.1 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis | 1.7 percent change | Standard Error 2.9 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis | 5.6 percent change | Standard Error 3.1 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis | 8.8 percent change | Standard Error 2.9 |
Secondary
Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment Apo-B value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis | -6.4 percent change | Standard Error 4.2 |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis | -20.9 percent change | Standard Error 4.2 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis | -20.9 percent change | Standard Error 4 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis | -28.4 percent change | Standard Error 4.3 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis | -50.2 percent change | Standard Error 4 |
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint..
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one on-treatment HDL-C value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis | 2.2 percent change | Standard Error 3.7 |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis | 7.9 percent change | Standard Error 3.7 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis | 6.5 percent change | Standard Error 3.5 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis | 1.00 percent change | Standard Error 3.8 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis | 12.3 percent change | Standard Error 3.6 |
Secondary
Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range)
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment lipoprotein(a) value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -3.9 percent change |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -10.1 percent change |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -7.5 percent change |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -15.3 percent change |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | -23.4 percent change |
Secondary
Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment non-HDL-C value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -11.3 percent change | Standard Error 4.7 |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -26.8 percent change | Standard Error 4.8 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -27.4 percent change | Standard Error 4.6 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -39.0 percent change | Standard Error 4.8 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | -57.9 percent change | Standard Error 4.6 |
Secondary
Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one on-treatment total cholesterol value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -8.5 percent change | Standard Error 3.8 |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -18.1 percent change | Standard Error 3.9 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -19.7 percent change | Standard Error 3.7 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -25.7 percent change | Standard Error 3.8 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | -43.6 percent change | Standard Error 3.7 |
Secondary
Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)
Time frame: From Baseline to Week 12 (LOCF)
Population: mITT population included all randomized participants with one baseline and at least one post baseline on-treatment fasting triglycerides value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis | -10.6 percent change |
| Alirocumab 150 mg Q4W | Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis | -16.7 percent change |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis | -13.2 percent change |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis | -4.9 percent change |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis | -16.2 percent change |