Hypercholesterolaemia
Conditions
Brief summary
Primary Objective: To evaluate the efficacy of alirocumab administered every 2 weeks (Q2W) and every 4 weeks (Q4W) versus placebo after 24 weeks of double-blind (DB) treatment on low-density lipoprotein cholesterol (LDL-C) levels in participants with heterozygous familial hypercholesterolemia (heFH) 8 to 17 years of age 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. Secondary Objectives: * To evaluate the efficacy of alirocumab versus placebo on LDL-C levels. * To evaluate the effects of alirocumab versus placebo on other lipid parameters. * To evaluate the safety and tolerability of alirocumab in comparison with placebo. * To evaluate the efficacy, safety, and tolerability of alirocumab after open label treatment. * To evaluate the development of anti-alirocumab antibodies.
Detailed description
The study duration was approximately up to 110 weeks (run-in period \[if needed\]: up to 4 weeks \[+2 days\], screening period: up to 2 weeks \[+5 days\], double-blind treatment period: 24 weeks, open label (OL) treatment period: 80 weeks).
Interventions
Pharmaceutical form:solution Route of administration: subcutaneous injection
DRUGRosuvastatin
Pharmaceutical form:tablet Route of administration: oral
DRUGAtorvastatin
Pharmaceutical form:Tablet Route of administration: Oral
DRUGSimvastatin
Pharmaceutical form:Tablet Route of administration: Oral
DRUGPravastatin
Pharmaceutical form:Tablet Route of administration: Oral
DRUGLovastatin
Pharmaceutical form:Tablet Route of administration: Oral
DRUGFluvastatin
Pharmaceutical form:Capsule Route of administration: Oral
DRUGEzetimibe
Pharmaceutical form:Tablet Route of administration: Oral
DRUGCholestyramine
Pharmaceutical form:oral suspension Route of administration: oral
DRUGNicotinic acid
Pharmaceutical form:Tablet Route of administration: Oral
DRUGFenofibrate
Pharmaceutical form:Tablet Route of administration: Oral
DRUGOmega-3 fatty acids
Pharmaceutical form:capsule Route of administration: oral
DRUGPlacebo
Pharmaceutical form:solution Route of administration: subcutaneous injection
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Children and adolescent male and female participants 8 to 17 years of age at the time of signed informed consent. * Participants with diagnosis of 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 except for participants who have previously participated in the DFI14223 (NCT02890992) study. * A signed informed consent indicating parental permission with or without participant assent.
Exclusion criteria
* Participant with body weight \< 25 kg. * Participants aged of 8 to 9 years not at Tanner stage 1 and participants aged of 10 to 17 years not at least at Tanner stage 2 in their development. * Participants 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. * Participants with uncontrolled type 1 or type 2 diabetes mellitus. * Participants with known uncontrolled thyroid disease. * Participants with uncontrolled hypertension. * Fasting triglycerides greater than (\>) 350 mg/dL (3.95 mmol/L). * Severe renal impairment (ie, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2). * Alanine aminotransferase or aspartate aminotransferase \>2\*upper limit of normal (ULN). * Creatinine phosphokinase (CPK) \>3\*ULN. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand | Baseline, Week 24 | Adjusted least square (LS) means and standard errors (SE) were obtained from mixed-effect model with repeated measures (MMRM) model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand | Baseline, Week 24 | Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand | Baseline, Week 24 | Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand | Baseline, Week 24 | Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand | At Week 24 | Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 24 were included in the imputation model. |
| DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand | At Week 12 | Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 12 were included in the imputation model. |
| DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand | At Week 24 | Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 24 were included in the imputation model. |
| DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand | At Week 12 | Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data for Q4W. All available post-baseline data up to Week 12 were included in the imputation model. For Q2W, adjusted percentages at Week 12 were obtained from last observation carried forward approach (LOCF) to handle missing on-treatment LDL-C values as well as missing post-treatment LDL-C values in participants who discontinued treatment due to the coronavirus disease-2019 pandemic. Other post-treatment missing values were considered as failure. |
| DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand | Baseline, Week 24 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. |
| DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 12. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. |
| DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12 and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. |
| DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand | Baseline, Week 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand | Baseline, Week 24 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. |
| DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand | Baseline, Week 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 12. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. |
| DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Baseline, Weeks 12, and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st investigational medicinal product (IMP) injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. |
| DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12 and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. |
| DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12 and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. |
| DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Weeks 12 and 24 | Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. |
| DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Weeks 12 and 24 | Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. |
| DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12 and 24 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline on-treatment data up to Week 12 and Week 24, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. |
| DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12 and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM mode, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. |
| DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12, and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 day otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. |
| DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12, and 24 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline on-treatment data up to Week 12 and Week 24, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. |
| DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Baseline, Weeks 12, and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 and Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Baseline, Weeks 12, and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. |
| DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | At Weeks 12 and 24 | Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model. |
| DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | At Weeks 12 and 24 | Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. |
| DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | At Weeks 12 and 24 | Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model. |
| DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | At Weeks 12 and 24 | Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. |
| DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Baseline to Weeks 8, 12 and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 8, Week 12 and Week 24 were used and missing data were accounted for by the MMRM model. |
| DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Baseline to Weeks 8, 12 and 24 | Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 8, Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. |
| DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand | Baseline, Week 12 | Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. |
| OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand | Baseline, Week 104 | Percent Change in LDL-C from Baseline to Week 104 was reported in this outcome measure. |
| Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Baseline, Weeks 24, 68 and 104 | Cogstate battery test (cognitive testing system) consisted of detection test (DET), identification test (IDN), one card learning test (OCL) and Groton maze learning test (GML) to assess processing speed, attention, visual learning and executive functioning, respectively. For each test, Z-scores were computed based on participant's age at Baseline and Weeks 24, 68 and 104. Composite score: calculated as mean of Z-scores equally weighted, provided that at least 3 of 4 tests were available and if all of these domains were covered as: attention, through either DET or IDN, visual learning, through OCL and executive function, through GML. There is not minimum/maximum since values were reported as z-score but z-score of 0 means result equals to mean with negative numbers indicating values lower than mean and positive values higher. Positive change in z-score = an improvement in cognition, i.e., a better outcome; and negative change in z-score = worsening in cognition, i.e., a worse outcome. |
| Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline, Weeks 24, 68 and 104 | Tanner stage defines physical measurements of development in children and adolescent based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males) and classified in 3 categories as: Prepubescent (defined as a person just before start of the development of adult sexual characteristics), Pubescent (defined as a person at or approaching the age of puberty), Postpubescent (sexually mature or a person who has completed puberty). |
| DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response | Up to 24 weeks | Anti-drug (alirocumab) antibodies samples were analyzed using a validated non-quantitative, titer-based bridging immunoassay. Number of participants with positive ADA during 24-week treatment period is reported. Treatment-emergent positive ADA response was defined as 1) participants with no ADA positive response at baseline but with any positive response in the post-baseline period or 2) participants with a positive ADA response at baseline and at least a 4- fold increase in titer in the post-baseline period. A persistent positive response was defined as a TE ADA positive response detected in at least 2 consecutive post-baseline samples separated by at least a 12-week period. Persistent positive response was only analyzed for participants with positive TE ADA response. |
| OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand | Baseline, Week 104 | Percent Change in LDL-C from Baseline to Week 104 was reported in this outcome measure. |
Countries
Argentina, Austria, Brazil, Bulgaria, Canada, Czechia, Denmark, Finland, France, Hungary, Italy, Lebanon, Mexico, Netherlands, Norway, Poland, Russia, Slovenia, South Africa, Spain, Sweden, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
Study was conducted at 43 active sites in 24 countries. A total of 203 participants were screened between 31-May-2018 and 31-Jul-2020, of whom 50 were screen failures. Screen failures were mainly due to exclusion criteria met. A total of 153 participants were randomized with a 2:1 ratio to receive study treatment (alirocumab: placebo).
Pre-assignment details
Randomization was stratified according to previous participation (yes or no) in the Phase 2 DFI14223 (NCT02890992) study and Baseline body weight (BW) (less than \[\<\] 50 kilograms (kg) or greater than or equal to \[\>=\] 50 kg).
Participants by arm
| Arm | Count |
|---|---|
| DB Period: Placebo Q2W Participants received SC injection of placebo (matched to alirocumab) based on their BW (\<50 kg or \>=50 kg) Q2W for 24 weeks in DB treatment period along with LMT. | 25 |
| DB Period: Alirocumab Q2W Participants received SC injection of alirocumab 40 mg (for BW \<50 kg) or 75 mg (for BW \>=50 kg) Q2W for 24 weeks in DB treatment period along with LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level was \>=110 mg/dL (2.85 mmol/L) at Week 8. | 49 |
| DB Period: Placebo Q4W Participants received SC injection of placebo (matched to alirocumab) based on their BW (\<50 kg or \>=50 kg) Q4W for 24 weeks in DB treatment period along with LMT. | 27 |
| DB Period: Alirocumab Q4W Participants received SC injection of alirocumab 150 mg (for BW \<50 kg) or 300 mg (for BW \>=50 kg) Q4W for 24 weeks in DB treatment period along with LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level \>=110 mg/dL (2.85 mmol/L) at Week 8. | 52 |
| Total Title | 153 |
| Total | 306 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Period (up to Week 24) | Adverse Event | 0 | 0 | 0 | 2 |
| Double-blind Period (up to Week 24) | Life events made continuing too difficult | 0 | 1 | 0 | 0 |
| Double-blind Period (up to Week 24) | Other than specified above | 0 | 0 | 1 | 1 |
| Double-blind Period (up to Week 24) | Participant moved | 0 | 1 | 0 | 0 |
| Double-blind Period (up to Week 24) | Participant non-compliance to investigational medicinal product (IMP) | 0 | 2 | 0 | 0 |
| Open Label Period (up to Week 104) | Adverse Event | 1 | 0 | 0 | 0 |
| Open Label Period (up to Week 104) | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Open Label Period (up to Week 104) | Life events made continuing too difficult | 0 | 1 | 0 | 0 |
| Open Label Period (up to Week 104) | Other than specified above | 1 | 1 | 0 | 0 |
| Open Label Period (up to Week 104) | Participant moved | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | DB Period: Placebo Q2W | Total Title | DB Period: Alirocumab Q4W | DB Period: Placebo Q4W | DB Period: Alirocumab Q2W |
|---|---|---|---|---|---|
| Age, Continuous | 13.2 years STANDARD_DEVIATION 2.4 | 12.9 years STANDARD_DEVIATION 2.8 | 13.1 years STANDARD_DEVIATION 3 | 12.8 years STANDARD_DEVIATION 3 | 12.5 years STANDARD_DEVIATION 2.7 |
| Low-Density Lipoprotein Cholesterol (LDL-C) | 175.29 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 50.23 | 174.23 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 49.85 | 176.79 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 53.93 | 176.57 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 49.01 | 169.69 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 46.74 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 16 Participants | 12 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 125 Participants | 38 Participants | 22 Participants | 42 Participants |
| Sex: Female, Male Female | 8 Participants | 87 Participants | 34 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 17 Participants | 66 Participants | 18 Participants | 12 Participants | 19 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 49 | 0 / 27 | 0 / 52 | 0 / 25 | 0 / 46 | 0 / 25 | 0 / 49 |
| other Total, other adverse events | 9 / 25 | 15 / 49 | 8 / 27 | 10 / 52 | 9 / 25 | 12 / 46 | 6 / 25 | 15 / 49 |
| serious Total, serious adverse events | 1 / 25 | 4 / 49 | 1 / 27 | 2 / 52 | 0 / 25 | 4 / 46 | 2 / 25 | 3 / 49 |
Outcome results
Primary
DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand
Adjusted least square (LS) means and standard errors (SE) were obtained from mixed-effect model with repeated measures (MMRM) model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population which included all randomized participants who were analyzed according to the treatment group allocated by randomization. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand | 9.7 percent change | Standard Error 4.3 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand | -33.6 percent change | Standard Error 3.4 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand | -4.4 percent change | Standard Error 3.7 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand | -38.2 percent change | Standard Error 4 |
Comparison: The MMRM model included fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per interactive voice response system (IVRS), time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline LDL-C value and Baseline value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-56, -30.7]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline LDL-C value and Baseline value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-46.4, -21.2]MMRM
Secondary
Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104
Cogstate battery test (cognitive testing system) consisted of detection test (DET), identification test (IDN), one card learning test (OCL) and Groton maze learning test (GML) to assess processing speed, attention, visual learning and executive functioning, respectively. For each test, Z-scores were computed based on participant's age at Baseline and Weeks 24, 68 and 104. Composite score: calculated as mean of Z-scores equally weighted, provided that at least 3 of 4 tests were available and if all of these domains were covered as: attention, through either DET or IDN, visual learning, through OCL and executive function, through GML. There is not minimum/maximum since values were reported as z-score but z-score of 0 means result equals to mean with negative numbers indicating values lower than mean and positive values higher. Positive change in z-score = an improvement in cognition, i.e., a better outcome; and negative change in z-score = worsening in cognition, i.e., a worse outcome.
Time frame: Baseline, Weeks 24, 68 and 104
Population: Analysis was performed on safety population which consisted of the randomized population who had actually received at least one dose or partial dose of IMP. Here, number analyzed = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 104 | -0.601 Z-score | Standard Deviation 1.612 |
| DB Period: Placebo Q2W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 68 | -0.421 Z-score | Standard Deviation 1.752 |
| DB Period: Placebo Q2W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 24 | -0.403 Z-score | Standard Deviation 1.008 |
| DB Period: Alirocumab Q2W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 68 | -0.334 Z-score | Standard Deviation 0.912 |
| DB Period: Alirocumab Q2W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 24 | -0.313 Z-score | Standard Deviation 0.444 |
| DB Period: Alirocumab Q2W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 104 | -0.439 Z-score | Standard Deviation 0.917 |
| DB Period: Placebo Q4W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 104 | -0.393 Z-score | Standard Deviation 0.764 |
| DB Period: Placebo Q4W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 24 | -0.218 Z-score | Standard Deviation 0.501 |
| DB Period: Placebo Q4W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 68 | -0.272 Z-score | Standard Deviation 0.814 |
| DB Period: Alirocumab Q4W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 24 | -0.136 Z-score | Standard Deviation 0.637 |
| DB Period: Alirocumab Q4W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 104 | -0.638 Z-score | Standard Deviation 0.791 |
| DB Period: Alirocumab Q4W | Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 | Week 68 | -0.263 Z-score | Standard Deviation 0.717 |
Secondary
DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 and Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Weeks 12, and 24
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 12 | 0.1 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Placebo Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 24 | 0.1 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 24 | -0.2 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 12 | -0.2 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Placebo Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 12 | 0.0 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Placebo Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 24 | 0.0 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 12 | -0.3 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand | Week 24 | -0.3 ratio (Apo B/Apo A-1) | Standard Error 0 |
Secondary
DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model.
Time frame: Baseline, Weeks 12, and 24
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 12 | 0.1 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Placebo Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 24 | 0.1 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 24 | -0.2 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q2W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 12 | -0.2 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Placebo Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 12 | 0.0 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Placebo Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 24 | 0.0 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 12 | -0.3 ratio (Apo B/Apo A-1) | Standard Error 0 |
| DB Period: Alirocumab Q4W | DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand | Week 24 | -0.3 ratio (Apo B/Apo A-1) | Standard Error 0 |
Secondary
DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response
Anti-drug (alirocumab) antibodies samples were analyzed using a validated non-quantitative, titer-based bridging immunoassay. Number of participants with positive ADA during 24-week treatment period is reported. Treatment-emergent positive ADA response was defined as 1) participants with no ADA positive response at baseline but with any positive response in the post-baseline period or 2) participants with a positive ADA response at baseline and at least a 4- fold increase in titer in the post-baseline period. A persistent positive response was defined as a TE ADA positive response detected in at least 2 consecutive post-baseline samples separated by at least a 12-week period. Persistent positive response was only analyzed for participants with positive TE ADA response.
Time frame: Up to 24 weeks
Population: Analysis was performed on ADA population which included all randomized and treated (who actually received at least one dose or part of a dose of the IMP injection) participants with an available ADA sample at Baseline (Week 0) and at least 1 non-missing ADA sample post first IMP injection and up to Week 24/early termination. Here, 'number analyzed' = participants with available data for each specified category and '0' in number analyzed filed signifies that no participants were evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response | TE ADA positive response | 0 Participants |
| DB Period: Alirocumab Q2W | DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response | TE ADA positive response | 3 Participants |
| DB Period: Alirocumab Q2W | DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response | Persistent positive response | 0 Participants |
| DB Period: Placebo Q4W | DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response | TE ADA positive response | 0 Participants |
| DB Period: Alirocumab Q4W | DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response | TE ADA positive response | 0 Participants |
Secondary
DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand
Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise.
Time frame: At Weeks 12 and 24
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 0.8 percentage of participants |
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 4.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 66.7 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 65.8 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 4.2 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 18.5 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 70.8 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 72.5 percentage of participants |
Secondary
DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand
Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data for Q4W. All available post-baseline data up to Week 12 were included in the imputation model. For Q2W, adjusted percentages at Week 12 were obtained from last observation carried forward approach (LOCF) to handle missing on-treatment LDL-C values as well as missing post-treatment LDL-C values in participants who discontinued treatment due to the coronavirus disease-2019 pandemic. Other post-treatment missing values were considered as failure.
Time frame: At Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand | 0.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand | 61.2 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand | 4.3 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand | 57.0 percentage of participants |
Comparison: The LOCF approach followed by exact conditional logistic regression model. The exact conditional logistic regression model stratified by randomization factors (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the quartiles of the Baseline LDL-C value.p-value: <0.0001Exact conditional logistic regression
Comparison: Multiple imputation approach followed by logistic regression model. The logistic regression model stratified by randomization factors (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the continuous fixed covariate of Baseline LDL-C value.p-value: =0.000597.5% CI: [5.2, 2095.9]Regression, Logistic
Secondary
DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand
Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 24 were included in the imputation model.
Time frame: At Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand | 4.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand | 57.2 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand | 9.0 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand | 67.2 percentage of participants |
Comparison: Multiple imputation approach followed by logistic regression model. The logistic regression model stratified by randomization factors (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the continuous fixed covariate of Baseline LDL-C value.p-value: =0.001197.5% CI: [3.5, 804.3]Regression, Logistic
Comparison: Multiple imputation approach followed by logistic regression model. The logistic regression model stratified by randomization factors (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the continuous fixed covariate of Baseline LDL-C value.p-value: =0.000697.5% CI: [3.7, 498.6]Regression, Logistic
Secondary
DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand
Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model.
Time frame: At Weeks 12 and 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week12 | 0.8 percentage of participants |
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 4.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 66.7 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week12 | 65.8 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 18.5 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week12 | 4.2 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week12 | 70.8 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 72.5 percentage of participants |
Secondary
DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand
Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model.
Time frame: At Weeks 12 and 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 12 | 0.0 percentage of participants |
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 0.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 21.6 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 12 | 25.2 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 9.1 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 12 | 0.1 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 12 | 31.9 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand | Week 24 | 32.4 percentage of participants |
Secondary
DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand
Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise.
Time frame: At Weeks 12 and 24
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 0.0 percentage of participants |
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 0.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 25.2 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 21.6 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 0.1 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 9.1 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 24 | 32.4 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand | Week 12 | 31.9 percentage of participants |
Secondary
DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand
Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise.
Time frame: Weeks 12 and 24
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 0.1 percentage of participants |
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 4.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 57.2 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 61.7 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 4.3 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 9.0 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 57.0 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 67.2 percentage of participants |
Secondary
DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand
Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise.
Time frame: Weeks 12 and 24
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 16.4 percentage of participants |
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 8.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 73.3 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 70.6 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 12.9 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 22.2 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 72.6 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 76.3 percentage of participants |
Secondary
DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand
Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 12 were included in the imputation model.
Time frame: At Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand | 16.4 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand | 70.6 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand | 12.9 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand | 72.6 percentage of participants |
Comparison: Multiple imputation approach followed by logistic regression model. The logistic regression model stratified by randomization factors (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the continuous fixed covariate of Baseline LDL-C value.p-value: <0.000197.5% CI: [4, 174.8]Regression, Logistic
Comparison: Multiple imputation approach followed by logistic regression model. The logistic regression model stratified by randomization factors (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the continuous fixed covariate of Baseline LDL-C value.p-value: <0.000197.5% CI: [5.7, 290.9]Regression, Logistic
Secondary
DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand
Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 24 were included in the imputation model.
Time frame: At Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand | 8.0 percentage of participants |
| DB Period: Alirocumab Q2W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand | 73.3 percentage of participants |
| DB Period: Placebo Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand | 22.2 percentage of participants |
| DB Period: Alirocumab Q4W | DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand | 76.3 percentage of participants |
Comparison: Multiple imputation approach followed by logistic regression model. Logistic regression model stratified by randomization factors (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the continuous fixed covariate of Baseline LDL-C value.p-value: =0.000197.5% CI: [6.3, 960]Regression, Logistic
Comparison: Multiple imputation approach followed by logistic regression model. Logistic regression model stratified by randomization factors (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS included the fixed categorical effect of treatment group and the continuous fixed covariate of Baseline LDL-C value.p-value: <0.000197.5% CI: [3.2, 69.8]Regression, Logistic
Secondary
DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand | -0.1 percent change | Standard Error 2.6 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand | 1.0 percent change | Standard Error 1.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand | -4.5 percent change | Standard Error 2.6 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand | 4.4 percent change | Standard Error 2 |
Secondary
DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand | -0.1 percent change | Standard Error 1.8 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand | -1.7 percent change | Standard Error 1.7 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand | -0.7 percent change | Standard Error 3.1 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand | 5.0 percent change | Standard Error 1.7 |
Secondary
DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM mode, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model.
Time frame: Baseline, Weeks 12 and 24
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 12 | -0.1 percent change | Standard Error 1.8 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 24 | -0.1 percent change | Standard Error 2.6 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 12 | -1.7 percent change | Standard Error 1.7 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 24 | 1.0 percent change | Standard Error 1.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 24 | -4.5 percent change | Standard Error 2.6 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 12 | -0.7 percent change | Standard Error 3.1 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 12 | 5.0 percent change | Standard Error 1.7 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand | Week 24 | 4.4 percent change | Standard Error 2 |
Secondary
DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand | 10.4 percent change | Standard Error 2.8 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand | -27.4 percent change | Standard Error 3.2 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand | -3.6 percent change | Standard Error 3.9 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand | -34.3 percent change | Standard Error 2.9 |
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Apo B value and Baseline Apo B value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-47.5, -28.2]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Apo B value and Baseline Apo B value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-42, -19.4]MMRM
Secondary
DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand | 8.9 percent change | Standard Error 3.1 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand | -30.0 percent change | Standard Error 2.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand | 1.1 percent change | Standard Error 3.2 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand | -31.7 percent change | Standard Error 2.9 |
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Apo B value and Baseline Apo B value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-48.2, -29.6]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Apo B value and Baseline Apo B value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-42.8, -22.7]MMRM
Secondary
DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model.
Time frame: Baseline, Weeks 12 and 24
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 12 | 8.9 percent change | Standard Error 3.1 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 24 | 10.4 percent change | Standard Error 2.8 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 24 | -27.4 percent change | Standard Error 3.2 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 12 | -30.0 percent change | Standard Error 2.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 24 | -3.6 percent change | Standard Error 3.9 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 12 | 1.1 percent change | Standard Error 3.2 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 12 | -31.7 percent change | Standard Error 2.9 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand | Week 24 | -34.3 percent change | Standard Error 2.9 |
Secondary
DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline on-treatment data up to Week 12 and Week 24, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets.
Time frame: Baseline, Weeks 12, and 24
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 12 | 6.5 percent change | Standard Error 7.4 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 24 | 7.7 percent change | Standard Error 8.4 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 24 | 11.9 percent change | Standard Error 6.3 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 12 | -2.2 percent change | Standard Error 5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 24 | 12.2 percent change | Standard Error 8.2 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 12 | 7.8 percent change | Standard Error 8.4 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 24 | -6.8 percent change | Standard Error 5.5 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand | Week 12 | -0.3 percent change | Standard Error 6 |
Secondary
DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 12. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand | 6.5 percent change | Standard Error 7.4 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand | -2.2 percent change | Standard Error 5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand | 7.8 percent change | Standard Error 8.4 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand | -0.3 percent change | Standard Error 6 |
Secondary
DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand | 7.7 percent change | Standard Error 8.4 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand | 11.9 percent change | Standard Error 6.3 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand | 12.2 percent change | Standard Error 8.2 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand | -6.8 percent change | Standard Error 5.5 |
Secondary
DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand | -2.2 percent change | Standard Error 3.2 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand | 3.5 percent change | Standard Error 2 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand | -3.5 percent change | Standard Error 3.2 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand | 4.0 percent change | Standard Error 2.2 |
Secondary
DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand | -0.8 percent change | Standard Error 2.1 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand | 5.6 percent change | Standard Error 1.4 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand | -1.1 percent change | Standard Error 2.7 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand | 3.4 percent change | Standard Error 2.1 |
Secondary
DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 day otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model.
Time frame: Baseline, Weeks 12, and 24
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 12 | -2.2 percent change | Standard Error 3.2 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 24 | -0.8 percent change | Standard Error 2.1 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 5.6 percent change | Standard Error 1.4 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 3.5 percent change | Standard Error 2 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 12 | -3.5 percent change | Standard Error 3.2 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 24 | -1.1 percent change | Standard Error 2.7 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 12 | 4.0 percent change | Standard Error 2.2 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 3.4 percent change | Standard Error 2.1 |
Secondary
DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 12. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand | -7.1 percent change | Standard Error 5.9 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand | -12.7 percent change | Standard Error 3.9 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand | -2.5 percent change | Standard Error 6.9 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand | -16.0 percent change | Standard Error 5.1 |
Comparison: Multiple imputation approach followed by robust regression model. The robust regression model included the fixed categorical effect of treatment group and randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS and the continuous fixed covariate of Baseline lipoprotein (a) value.p-value: =0.428897.5% CI: [-21.7, 10.4]Robust regression model
Comparison: Multiple imputation approach followed by robust regression model. The robust regression model included the fixed categorical effect of treatment group and randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS and the continuous fixed covariate of Baseline lipoprotein (a) value.p-value: =0.114897.5% CI: [-32.7, 5.7]Robust regression model
Secondary
DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand | 0.5 percent change | Standard Error 5.3 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand | -14.7 percent change | Standard Error 4.1 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand | 2.5 percent change | Standard Error 7.1 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand | -22.4 percent change | Standard Error 5 |
Comparison: Multiple imputation approach followed by robust regression model. The robust regression model included the fixed categorical effect of treatment group and randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS and the continuous fixed covariate of Baseline lipoprotein (a) value.p-value: =0.023797.5% CI: [-30.3, -0.1]Robust regression model
Comparison: Multiple imputation approach followed by robust regression model. The robust regression model included the fixed categorical effect of treatment group and randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS and the continuous fixed covariate of Baseline lipoprotein (a) value.p-value: =0.004397.5% CI: [-44.4, -5.4]Robust regression model
Secondary
DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline on-treatment data up to Week 12 and Week 24, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets.
Time frame: Baseline, Weeks 12 and 24
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 12 | -7.099 percent change | Standard Error 5.923 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 0.492 percent change | Standard Error 5.254 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 12 | -12.746 percent change | Standard Error 3.889 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 24 | -14.748 percent change | Standard Error 4.083 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 24 | 2.468 percent change | Standard Error 7.135 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 12 | -2.545 percent change | Standard Error 6.851 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 12 | -16.042 percent change | Standard Error 5.139 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand | Week 24 | -22.418 percent change | Standard Error 5.03 |
Secondary
DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand | 10.7 percent change | Standard Error 3.6 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand | -34.8 percent change | Standard Error 3 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand | 2.3 percent change | Standard Error 3.6 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand | -39.2 percent change | Standard Error 3.3 |
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline LDL-C value and Baseline value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-56.3, -34.7]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline LDL-C value and Baseline value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-52.7, -30.2]MMRM
Secondary
DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st investigational medicinal product (IMP) injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model.
Time frame: Baseline, Weeks 12, and 24
Population: Analysis was performed on modified intent-to-treat (mITT) population which included all randomized participants who took at least one dose or part of a dose of the IMP injection. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 12 | 10.7 percent change | Standard Error 3.6 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 24 | 9.7 percent change | Standard Error 4.3 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 24 | -33.6 percent change | Standard Error 3.4 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 12 | -34.8 percent change | Standard Error 3 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 12 | 2.3 percent change | Standard Error 3.6 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 24 | -4.4 percent change | Standard Error 3.7 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 12 | -39.2 percent change | Standard Error 3.3 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand | Week 24 | -38.2 percent change | Standard Error 4 |
Secondary
DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand | 9.8 percent change | Standard Error 3.8 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand | -33.0 percent change | Standard Error 2.8 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand | 2.8 percent change | Standard Error 3.5 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand | -34.7 percent change | Standard Error 2.9 |
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Non-HDL-C value and Baseline Non-HDL-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-53.8, -31.8]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline non-HDL-C value and Baseline non-HDL-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-47.9, -27]MMRM
Secondary
DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model.
Time frame: Baseline, Weeks 12 and 24
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | 9.8 percent change | Standard Error 3.8 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | 9.7 percent change | Standard Error 3.9 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | -31.0 percent change | Standard Error 3.2 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | -33.0 percent change | Standard Error 2.8 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | -3.7 percent change | Standard Error 4 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | 2.8 percent change | Standard Error 3.5 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | -35.6 percent change | Standard Error 3.5 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | -34.7 percent change | Standard Error 2.9 |
Secondary
DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand | 9.7 percent change | Standard Error 3.9 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand | -31.0 percent change | Standard Error 3.2 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand | -3.7 percent change | Standard Error 4 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand | -35.6 percent change | Standard Error 3.5 |
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline non-HDL-C value and Baseline non-HDL-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-52.2, -29.1]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline non-HDL-C value and Baseline non-HDL-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-44.1, -19.7]MMRM
Secondary
DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand | 7.5 percent change | Standard Error 2.9 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand | -25.3 percent change | Standard Error 2.2 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand | 0.9 percent change | Standard Error 2.5 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand | -27.0 percent change | Standard Error 2.3 |
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Total-C value and Baseline Total-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-41.3, -24.2]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Total-C value and Baseline Total-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-35.6, -20.2]MMRM
Secondary
DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model.
Time frame: Baseline, Weeks 12 and 24
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | 7.4 percent change | Standard Error 3 |
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | 7.5 percent change | Standard Error 2.9 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | -25.3 percent change | Standard Error 2.2 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | -23.4 percent change | Standard Error 2.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | 0.9 percent change | Standard Error 2.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | -4.4 percent change | Standard Error 3.3 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 24 | -27.7 percent change | Standard Error 2.9 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand | Week 12 | -27.0 percent change | Standard Error 2.3 |
Secondary
DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand | 7.4 percent change | Standard Error 3 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand | -23.4 percent change | Standard Error 2.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand | -4.4 percent change | Standard Error 3.3 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand | -27.7 percent change | Standard Error 2.9 |
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (previous participation \[yes or no\] to DFI14223 study, Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Total-C value and Baseline Total-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-39.8, -21.9]MMRM
Comparison: The MMRM model included the fixed categorical effects of treatment group (alirocumab, placebo), randomization strata (Baseline BW \[\<50 or \>=50 kg\]) as per IVRS, time point, treatment-by-time point interaction, and BW strata-by-time point interaction, as well as the continuous fixed covariates of Baseline Total-C value and Baseline Total-C value by time-point interaction. Comparison was performed using an appropriate contrast.p-value: <0.000197.5% CI: [-33.5, -13.1]MMRM
Secondary
DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 8, Week 12 and Week 24 were used and missing data were accounted for by the MMRM model.
Time frame: Baseline to Weeks 8, 12 and 24
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 8 | 7.1 percent change | Standard Error 4.2 |
| DB Period: Placebo Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 24 | 9.7 percent change | Standard Error 4.3 |
| DB Period: Placebo Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 12 | 10.7 percent change | Standard Error 3.6 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 8 | -35.4 percent change | Standard Error 3.6 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 24 | -33.6 percent change | Standard Error 3.4 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 12 | -34.8 percent change | Standard Error 3 |
| DB Period: Placebo Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 12 | 2.3 percent change | Standard Error 3.6 |
| DB Period: Placebo Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 8 | -3.8 percent change | Standard Error 3.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 24 | -4.4 percent change | Standard Error 3.7 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 8 | -42.0 percent change | Standard Error 2.8 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 24 | -38.2 percent change | Standard Error 4 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand | Week 12 | -39.2 percent change | Standard Error 3.3 |
Secondary
DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand
Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 8, Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise.
Time frame: Baseline to Weeks 8, 12 and 24
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.~.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| DB Period: Placebo Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 8 | 7.1 percent change | Standard Error 4.2 |
| DB Period: Placebo Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 24 | 9.7 percent change | Standard Error 4.3 |
| DB Period: Placebo Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 12 | 10.7 percent change | Standard Error 3.6 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 8 | -35.4 percent change | Standard Error 3.6 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 24 | -33.6 percent change | Standard Error 3.4 |
| DB Period: Alirocumab Q2W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 12 | -34.8 percent change | Standard Error 3 |
| DB Period: Placebo Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 12 | 2.3 percent change | Standard Error 3.6 |
| DB Period: Placebo Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 8 | -3.8 percent change | Standard Error 3.5 |
| DB Period: Placebo Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 24 | -4.4 percent change | Standard Error 3.7 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 8 | -42.0 percent change | Standard Error 2.8 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 24 | -38.2 percent change | Standard Error 4 |
| DB Period: Alirocumab Q4W | DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand | Week 12 | -39.2 percent change | Standard Error 3.3 |
Secondary
Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104
Tanner stage defines physical measurements of development in children and adolescent based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males) and classified in 3 categories as: Prepubescent (defined as a person just before start of the development of adult sexual characteristics), Pubescent (defined as a person at or approaching the age of puberty), Postpubescent (sexually mature or a person who has completed puberty).
Time frame: Baseline, Weeks 24, 68 and 104
Population: Analysis was performed on safety population. Here, number analyzed = participants with available data for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Postpubescent | 4 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Pubescent | 5 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Prepubescent | 0 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Postpubescent | 2 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Prepubescent | 0 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Pubescent | 4 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Pubescent | 7 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Postpubescent | 2 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Postpubescent | 3 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Prepubescent | 0 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Prepubescent | 1 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Pubescent | 13 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Postpubescent | 1 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Postpubescent | 7 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Pubescent | 13 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Prepubescent | 1 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Pubescent | 6 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Pubescent | 6 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Prepubescent | 0 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Prepubescent | 0 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Postpubescent | 1 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Postpubescent | 4 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Pubescent | 6 Participants |
| DB Period: Placebo Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Prepubescent | 1 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Pubescent | 14 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Prepubescent | 3 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Prepubescent | 4 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Pubescent | 15 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Prepubescent | 1 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Postpubescent | 10 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Prepubescent | 3 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Prepubescent | 0 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Postpubescent | 6 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Postpubescent | 3 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Prepubescent | 1 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Prepubescent | 4 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Pubescent | 10 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Pubescent | 8 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Pubescent | 9 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Pubescent | 11 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Postpubescent | 11 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Pubescent | 16 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Postpubescent | 2 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Postpubescent | 9 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Prepubescent | 4 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Postpubescent | 6 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Postpubescent | 9 Participants |
| DB Period: Alirocumab Q2W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Pubescent | 13 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Pubescent | 4 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Prepubescent | 1 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Postpubescent | 3 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Postpubescent | 5 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Postpubescent | 5 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Prepubescent | 5 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Postpubescent | 3 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Prepubescent | 1 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Pubescent | 8 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Postpubescent | 6 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Pubescent | 7 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Prepubescent | 1 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Pubescent | 6 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Postpubescent | 5 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Prepubescent | 1 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Pubescent | 5 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Postpubescent | 3 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Prepubescent | 1 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Pubescent | 5 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Prepubescent | 1 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Pubescent | 5 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Postpubescent | 2 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Prepubescent | 1 Participants |
| DB Period: Placebo Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Pubescent | 5 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Prepubescent | 1 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Postpubescent | 5 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Pubescent | 12 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Postpubescent | 11 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Pubescent | 16 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Boys - Prepubescent | 0 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Girls - Postpubescent | 9 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Postpubescent | 14 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Postpubescent | 4 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Prepubescent | 0 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Pubescent | 13 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Girls - Prepubescent | 7 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Prepubescent | 1 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Pubescent | 8 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Pubescent | 14 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Baseline: Boys - Prepubescent | 0 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Pubescent | 9 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Prepubescent | 0 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Postpubescent | 9 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Girls - Pubescent | 17 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 68: Boys - Postpubescent | 6 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Pubescent | 16 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 24: Girls - Prepubescent | 2 Participants |
| DB Period: Alirocumab Q4W | Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 | Week 104: Boys - Postpubescent | 7 Participants |
Secondary
OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand
Percent Change in LDL-C from Baseline to Week 104 was reported in this outcome measure.
Time frame: Baseline, Week 104
Population: Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure. The IIT estimand was analyzed by considering all the post-baseline (including both on- and post-treatment) LDL-C values for the analysis.~.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand | -23.3 percent change | Standard Error 4.9 |
| DB Period: Alirocumab Q2W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand | -22.2 percent change | Standard Error 5.6 |
| DB Period: Placebo Q4W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand | -27.1 percent change | Standard Error 7 |
| DB Period: Alirocumab Q4W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand | -23.7 percent change | Standard Error 4.2 |
Secondary
OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand
Percent Change in LDL-C from Baseline to Week 104 was reported in this outcome measure.
Time frame: Baseline, Week 104
Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. The on-treatment estimand was analyzed using the same imputation model as ITT Estimand, but considered the 'on-treatment' LDL-C values alone for the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo Q2W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand | -22.8 percent change | Standard Error 5.1 |
| DB Period: Alirocumab Q2W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand | -25.8 percent change | Standard Error 4.9 |
| DB Period: Placebo Q4W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand | -27.6 percent change | Standard Error 7.6 |
| DB Period: Alirocumab Q4W | OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand | -23.4 percent change | Standard Error 4.7 |