Hypercholesterolaemia
Conditions
Brief summary
Primary Objective: To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) participants aged of 8 to 17 years, with LDL-C \>=130 milligrams per deciliter (mg/dL) (3.37 millimoles per litre \[mmol/L\]) on optimal stable daily dose of statin therapy +/- other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at least 4 weeks prior to the screening period. Secondary Objective: * To evaluate the safety and tolerability of alirocumab. * To evaluate the pharmacokinetics profile of alirocumab. * To evaluate the effects of alirocumab on other lipid parameters.
Detailed description
For Cohorts 1 to 3, a study duration of approximately 16-23 weeks (screening period: up to 6 (+1) weeks, open-label dose finding treatment period: 8 weeks, follow up period: 6-8 weeks). For Cohort 4, a study duration of approximately 14-19 weeks (screening period up to 6 \[+1\] weeks, open-label dose finding treatment period: 12 weeks). Optional extension period: up to a maximum of 2 years for the first participants enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first participants enrolled in Cohort 4. For all participants who declined participation in the phase 3 study, their last alirocumab injection was on December 2018.
Interventions
Pharmaceutical form: solution Route of administration: subcutaneous injection
DRUGstatins
Pharmaceutical form: tablet Route of administration: oral
DRUGezetimibe
Pharmaceutical form:tablet Route of administration: oral
DRUGcholestyramine
Pharmaceutical form:tablet Route of administration: oral
DRUGfenofibrate
Pharmaceutical form: tablet Route of administration: oral
DRUGomega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
DRUGnicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
: * Children and adolescent male and female participants aged of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female participants aged \>=12 and \<=17 years at the time of signed informed consent. * Participants with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria. * Participants treated with optimal dose of statin +/- other LMT(s) or non-statin LMT(s) if statin intolerant at stable dose for at least 4 weeks prior to screening lipid sampling. * Participants with calculated LDL-C greater than or equal to 130 mg/dL (\>=3.37 mmol/L) at the screening visit. * Participants with body weight greater than or equal to 25 kg. * Participants aged of 8 to 9 years to be at Tanner stage 1 and participants aged of 10 to 17 years to be at least at Tanner stage 2 in their development. * A signed informed consent indicating parental permission with or without participant assent.
Exclusion criteria
* Participant with secondary hyperlipidemia. * Diagnosis of homozygous familial hypercholesterolemia. * Participant who had received lipid apheresis treatment within 2 months prior to the screening period, or has plans to receive it during the study. * Known history of type 1 or type 2 diabetes mellitus. * Known history of thyroid disease. * Known history of hypertension. * Fasting triglycerides \>350 mg/dL (3.95 mmol/L). * Severe renal impairment (i.e., estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73 m\^2). * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 x upper limit of normal (ULN). * Creatinine phosphokinase (CPK) \>3 x ULN. 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 Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | Baseline, Week 8 | Percent change in calculated LDL-C was defined as 100\*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period & within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 & 2) or +35 days (for Cohorts 3 & 4). Adjusted Least-squares (LS) mean & standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W \[\<50 kg\], 40 mg Q2W \[\<50 kg\], 50 mg Q2W \[\>=50 kg\], 75 mg Q2W \[\>=50 kg\], 75 mg Q4W \[\<50 kg\],150 mg Q4W \[\>=50 kg\], 150 mg Q4W \[\<50 kg\] and 300 mg Q4W (\[\>=50 kg\] dose), time point & dose/dose regimen-by-time point interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | At Week 8 | Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
| Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | At Week 8 | Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
| Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4 | Baseline, Week 12 | Adjusted LS means and standard error at Week 12 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. |
| Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline value and post-baseline values in at least one of the analysis windows used in the model. |
| Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Percent Change From Baseline in Lipoprotein(a) at Week 8 | Baseline, Week 8 | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
| Percent Change From Baseline in Fasting Triglyceride at Week 8 | Baseline, Week 8 | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | Baseline, Week 8 | Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. |
| Absolute Change From Baseline in Apolipoprotein B at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Absolute Change From Baseline in Lipoprotein(a) at Week 8 | Baseline, Week 8 | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
| Absolute Change From Baseline in HDL-C at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Absolute Change From Baseline in Fasting Triglyceride at Week 8 | Baseline, Week 8 | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
| Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
| Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | Baseline, Week 8 | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Countries
Canada, Czechia, France, Netherlands, Norway, Russia, South Africa, Spain, Sweden, United States
Participant flow
Recruitment details
The study was conducted at 16 sites in 10 countries. Overall 63 participants were screened between 15 September 2016 and 13 June 2018, of whom 21 participants were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment details
A total of 42 participants were included in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | 4 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. | 6 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still \< 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | 4 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT.
Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. | 6 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT.
Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still \< 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was \> = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | 6 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT.
Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. | 5 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Period 1: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight \< 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 12 until Week 48. | 6 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg Period 1: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT.
Period 2: Participants with body weight \>= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. | 5 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| 130 Weeks Open-Label Extension Period | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| 130 Weeks Open-Label Extension Period | Included but not treated | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| 130 Weeks Open-Label Extension Period | Other than specified | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 11.0 years STANDARD_DEVIATION 2 | 13.8 years STANDARD_DEVIATION 2.7 | 11.3 years STANDARD_DEVIATION 2.2 | 14.3 years STANDARD_DEVIATION 2.3 | 9.8 years STANDARD_DEVIATION 1.9 | 13.8 years STANDARD_DEVIATION 1.6 | 11.3 years STANDARD_DEVIATION 2.2 | 13.6 years STANDARD_DEVIATION 2.1 | 12.4 years STANDARD_DEVIATION 2.6 |
| Low Density Lipoprotein Cholesterol (LDL-C) | 5.169 millimoles per litre (mmol/L) STANDARD_DEVIATION 0.736 | 4.339 millimoles per litre (mmol/L) STANDARD_DEVIATION 1.2 | 3.596 millimoles per litre (mmol/L) STANDARD_DEVIATION 0.63 | 4.510 millimoles per litre (mmol/L) STANDARD_DEVIATION 1.052 | 4.337 millimoles per litre (mmol/L) STANDARD_DEVIATION 1.147 | 4.642 millimoles per litre (mmol/L) STANDARD_DEVIATION 1.272 | 5.100 millimoles per litre (mmol/L) STANDARD_DEVIATION 1.136 | 4.641 millimoles per litre (mmol/L) STANDARD_DEVIATION 0.926 | 4.6 millimoles per litre (mmol/L) STANDARD_DEVIATION 1.1 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American/White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 3 Participants | 39 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 5 Participants | 3 Participants | 23 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 10 | 0 / 18 |
| other Total, other adverse events | 4 / 4 | 5 / 6 | 1 / 4 | 4 / 6 | 5 / 6 | 3 / 5 | 3 / 6 | 4 / 5 | 7 / 10 | 9 / 18 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 10 | 0 / 18 |
Outcome results
Primary
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
Percent change in calculated LDL-C was defined as 100\*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period & within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 & 2) or +35 days (for Cohorts 3 & 4). Adjusted Least-squares (LS) mean & standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W \[\<50 kg\], 40 mg Q2W \[\<50 kg\], 50 mg Q2W \[\>=50 kg\], 75 mg Q2W \[\>=50 kg\], 75 mg Q4W \[\<50 kg\],150 mg Q4W \[\>=50 kg\], 150 mg Q4W \[\<50 kg\] and 300 mg Q4W (\[\>=50 kg\] dose), time point & dose/dose regimen-by-time point interaction.
Time frame: Baseline, Week 8
Population: Analysis was performed on modified intent-to-treat (mITT) population which included all participants who received at least one dose or partial dose of IMP injection and had an evaluable outcome measure during the open-label dose finding efficacy treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -41.1 percent change | Standard Error 12.6 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -7.9 percent change | Standard Error 10.3 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -40.6 percent change | Standard Error 13.2 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -49.8 percent change | Standard Error 10.6 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -17.5 percent change | Standard Error 10.3 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | 4.0 percent change | Standard Error 11.2 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -31.9 percent change | Standard Error 10.3 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -59.8 percent change | Standard Error 11.2 |
Secondary
Absolute Change From Baseline in Apolipoprotein A-1 at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | 4.0 mg/dL | Standard Error 9.3 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | 17.7 mg/dL | Standard Error 6.5 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | 11.3 mg/dL | Standard Error 9.3 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | -0.4 mg/dL | Standard Error 7.2 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | 10.5 mg/dL | Standard Error 6.5 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | 8.0 mg/dL | Standard Error 7.2 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | 7.5 mg/dL | Standard Error 6.5 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 | 11.0 mg/dL | Standard Error 7.2 |
Secondary
Absolute Change From Baseline in Apolipoprotein B at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -51.7 mg/dL | Standard Error 15.8 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -18.5 mg/dL | Standard Error 11.1 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -35.3 mg/dL | Standard Error 15.8 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -53.4 mg/dL | Standard Error 12.2 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -15.3 mg/dL | Standard Error 11.1 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -5.4 mg/dL | Standard Error 12.2 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -34.2 mg/dL | Standard Error 11.1 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Apolipoprotein B at Week 8 | -63.5 mg/dL | Standard Error 12.2 |
Secondary
Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -83.7 milligram per deciliter (mg/dL) | Standard Error 19.5 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -27.6 milligram per deciliter (mg/dL) | Standard Error 15.9 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -55.5 milligram per deciliter (mg/dL) | Standard Error 20.8 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -88.3 milligram per deciliter (mg/dL) | Standard Error 16.5 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -32.4 milligram per deciliter (mg/dL) | Standard Error 15.9 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | 0.1 milligram per deciliter (mg/dL) | Standard Error 17.4 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -55.9 milligram per deciliter (mg/dL) | Standard Error 15.9 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 | -104.3 milligram per deciliter (mg/dL) | Standard Error 17.4 |
Secondary
Absolute Change From Baseline in Fasting Triglyceride at Week 8
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | -0.121 mmol/L | Standard Error 0.193 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | -0.076 mmol/L | Standard Error 0.157 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | 0.168 mmol/L | Standard Error 0.226 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | 0.111 mmol/L | Standard Error 0.188 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | 0.117 mmol/L | Standard Error 0.157 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | -0.045 mmol/L | Standard Error 0.172 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | -0.402 mmol/L | Standard Error 0.157 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Fasting Triglyceride at Week 8 | -0.107 mmol/L | Standard Error 0.172 |
Secondary
Absolute Change From Baseline in HDL-C at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 5.9 mg/dL | Standard Error 3.4 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 7.7 mg/dL | Standard Error 2.8 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 5.5 mg/dL | Standard Error 3.7 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 4.9 mg/dL | Standard Error 2.9 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 2.4 mg/dL | Standard Error 2.8 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 5.9 mg/dL | Standard Error 3.1 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 2.2 mg/dL | Standard Error 2.8 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in HDL-C at Week 8 | 1.2 mg/dL | Standard Error 3.1 |
Secondary
Absolute Change From Baseline in Lipoprotein(a) at Week 8
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | 0.003 gram/Liter (g/L) | Standard Error 0.022 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | -0.021 gram/Liter (g/L) | Standard Error 0.017 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | 0.007 gram/Liter (g/L) | Standard Error 0.073 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | -0.025 gram/Liter (g/L) | Standard Error 0.02 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | 0.023 gram/Liter (g/L) | Standard Error 0.018 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | -0.031 gram/Liter (g/L) | Standard Error 0.019 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | -0.002 gram/Liter (g/L) | Standard Error 0.017 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Lipoprotein(a) at Week 8 | -0.120 gram/Liter (g/L) | Standard Error 0.02 |
Secondary
Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -86.1 mg/dL | Standard Error 20.8 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -28.7 mg/dL | Standard Error 17 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -62.7 mg/dL | Standard Error 22.1 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -88.5 mg/dL | Standard Error 17.6 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -29.5 mg/dL | Standard Error 17 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -0.6 mg/dL | Standard Error 18.6 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -63.1 mg/dL | Standard Error 17 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 | -106.4 mg/dL | Standard Error 18.6 |
Secondary
Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.363 ratio (Apo B/Apo A-1) | Standard Error 0.123 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.262 ratio (Apo B/Apo A-1) | Standard Error 0.087 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.370 ratio (Apo B/Apo A-1) | Standard Error 0.123 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.402 ratio (Apo B/Apo A-1) | Standard Error 0.096 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.190 ratio (Apo B/Apo A-1) | Standard Error 0.087 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.086 ratio (Apo B/Apo A-1) | Standard Error 0.096 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.282 ratio (Apo B/Apo A-1) | Standard Error 0.087 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 | -0.473 ratio (Apo B/Apo A-1) | Standard Error 0.096 |
Secondary
Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -80.1 mg/dL | Standard Error 21.4 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -20.8 mg/dL | Standard Error 17.5 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -57.1 mg/dL | Standard Error 22.8 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -84.4 mg/dL | Standard Error 18.1 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -27.2 mg/dL | Standard Error 17.5 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | 5.3 mg/dL | Standard Error 19.1 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -60.7 mg/dL | Standard Error 17.5 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -105.1 mg/dL | Standard Error 19.1 |
Secondary
Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8
Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Time frame: At Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 0.0 percentage of participants |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 0.0 percentage of participants |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 93.4 percentage of participants |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 65.7 percentage of participants |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 16.7 percentage of participants |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 20.0 percentage of participants |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 66.7 percentage of participants |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 | 80.0 percentage of participants |
Secondary
Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8
Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Time frame: At Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 100.0 percentage of participants |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 33.3 percentage of participants |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 97.6 percentage of participants |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 83.0 percentage of participants |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 33.3 percentage of participants |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 20.0 percentage of participants |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 66.7 percentage of participants |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 | 80.0 percentage of participants |
Secondary
Percent Change From Baseline in Apolipoprotein A-1 at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 4.4 percent change | Standard Error 7.2 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 14.8 percent change | Standard Error 5.1 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 10.7 percent change | Standard Error 7.2 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 1.8 percent change | Standard Error 5.6 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 8.9 percent change | Standard Error 5.1 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 7.4 percent change | Standard Error 5.6 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 5.8 percent change | Standard Error 5.1 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 | 7.2 percent change | Standard Error 5.6 |
Secondary
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline value and post-baseline values in at least one of the analysis windows used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed=participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -38.4 percent change | Standard Error 12.8 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -9.7 percent change | Standard Error 9.1 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -36.4 percent change | Standard Error 12.8 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -40.1 percent change | Standard Error 9.9 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -12.6 percent change | Standard Error 9.1 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -0.9 percent change | Standard Error 9.9 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -27.2 percent change | Standard Error 9.1 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 | -51.4 percent change | Standard Error 9.9 |
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4
Adjusted LS means and standard error at Week 12 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.
Time frame: Baseline, Week 12
Population: Analysis was performed on mITT population. Data for this outcome measure was planned to be collected for Cohort 4 only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4 | -29.7 percent change | Standard Error 6.9 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4 | -49.2 percent change | Standard Error 7.5 |
Secondary
Percent Change From Baseline in Fasting Triglyceride at Week 8
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | -0.4 percent change | Standard Error 19.6 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | -4.0 percent change | Standard Error 16 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | -7.4 percent change | Standard Error 28.4 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | 14.5 percent change | Standard Error 19 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | 19.3 percent change | Standard Error 16 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | -3.1 percent change | Standard Error 17.5 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | -32.1 percent change | Standard Error 16 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in Fasting Triglyceride at Week 8 | -7.1 percent change | Standard Error 17.5 |
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 9.7 percent change | Standard Error 7.1 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 16.5 percent change | Standard Error 5.8 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 14.7 percent change | Standard Error 7.7 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 10.6 percent change | Standard Error 6.1 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 5.2 percent change | Standard Error 5.8 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 13.8 percent change | Standard Error 6.4 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 4.5 percent change | Standard Error 5.8 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 | 2.8 percent change | Standard Error 6.4 |
Secondary
Percent Change From Baseline in Lipoprotein(a) at Week 8
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | 4.5 percent change | Standard Error 21.1 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | -26.9 percent change | Standard Error 11.6 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | 1.5 percent change | Standard Error 15.1 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | -25.2 percent change | Standard Error 14.4 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | 2.2 percent change | Standard Error 10.5 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | -7.7 percent change | Standard Error 11.4 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | 0.1 percent change | Standard Error 10.2 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in Lipoprotein(a) at Week 8 | -7.7 percent change | Standard Error 11.1 |
Secondary
Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | -39.6 percent change | Standard Error 11.9 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | -7.1 percent change | Standard Error 9.7 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | -39.7 percent change | Standard Error 12.5 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | -43.9 percent change | Standard Error 10 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | -14.4 percent change | Standard Error 9.7 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | 3.2 percent change | Standard Error 10.7 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | -31.5 percent change | Standard Error 9.7 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 | -54.6 percent change | Standard Error 10.7 |
Secondary
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Time frame: Baseline, Week 8
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -29.0 percent change | Standard Error 9.7 |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -4.1 percent change | Standard Error 7.9 |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -28.6 percent change | Standard Error 10.1 |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -34.2 percent change | Standard Error 8.1 |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -10.7 percent change | Standard Error 7.9 |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | 5.2 percent change | Standard Error 8.6 |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -24.0 percent change | Standard Error 7.9 |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 | -41.8 percent change | Standard Error 8.6 |