Hypercholesterolemia
Conditions
Keywords
Pediatrics, Homozygous Familial Hypercholesterolemia, Alirocumab, PCSK9 inhibitor, Low-density Lipoprotein Cholesterol (LDL-C)
Brief summary
Primary Objective: To evaluate the efficacy of alirocumab (75 or 150 milligrams \[mg\] depending on body weight \[BW\]), administered every 2 weeks (Q2W), on low-density lipoprotein cholesterol (LDL-C) levels at Week 12 of treatment in children and adolescents with homozygous familial hypercholesterolemia (hoFH) of 8 to 17 years of age on top of background treatments. Secondary Objectives: * To evaluate the efficacy of alirocumab after 24 and 48 weeks of treatment on LDL-C levels. * To evaluate the effects of alirocumab on other lipid parameters (eg, apolipoprotein B \[Apo B\], non-high density lipoprotein cholesterol \[non-HDL-C\], total cholesterol \[Total-C\], high density lipoprotein cholesterol \[HDL-C\], lipoprotein a \[Lp (a)\], triglycerides \[TG\], apolipoprotein A-1 \[Apo A-1\] levels) after 12, 24, and 48 weeks of treatment. * To evaluate the safety and tolerability of alirocumab up to 48 weeks of treatment.
Detailed description
The study duration was up to 62 weeks, which included (if needed) a run-in period of up to 4 weeks, a screening period of up to 2 weeks, a treatment period of up to 48 weeks, and a follow-up of 8 weeks.
Interventions
Pharmaceutical form: solution for injection in pre-filled syringe, Route of administration: subcutaneous (SC)
DRUGAtorvastatin
Pharmaceutical form: tablet, Route of administration: oral
DRUGSimvastatin
Pharmaceutical form: tablet, Route of administration: oral
DRUGFluvastatin
Pharmaceutical form: capsule, Route of administration: oral
DRUGPravastatin
Pharmaceutical form: tablet, Route of administration: oral
DRUGLovastatin
Pharmaceutical form: tablet, Route of administration: oral
DRUGRosuvastatin
Pharmaceutical form: tablet, 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
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
: * Participants genetically diagnosed with hoFH. * Participants treated with optimal dose of statin +/- other lipid modifying therapies (LMTs), or non-statin LMTs if statin-intolerant at stable dose(s) for at least 4 weeks. * A signed informed consent indicating parental permission with or without participants assent. * For participants on apheresis, currently undergoing stable LDL apheresis therapy prior to the screening visit (Week -2) and had initiated apheresis treatment for at least 6 months.
Exclusion criteria
* Participants with LDL-C \<130 milligram per deciliter \[mg/dL\] (3.37 millimoles per liter \[mmol/L\]) obtained during the screening period after the participant had been on stable apheresis procedure or LMT (i.e., stable optimal dose of statin ± other stable LMTs, or stable non statin LMTs in statin-intolerant participants) treatment for at least 4 weeks. * Participants with BW \<25 kg. * Participants aged 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 uncontrolled Type 1 or 2 diabetes mellitus. * Participants with known uncontrolled thyroid disease. * Participants with uncontrolled hypertension. * Participants who will receive statin de novo during the run-in period. * Fasting triglycerides greater than (\>) 350 mg/dL (3.95 mmol/L) at the screening visit. * Severe renal impairment (i.e., estimated glomerular filtration rate \<30 milliliter per minute/1.73 meter square) at the screening visit. * Alanine aminotransferase or aspartate aminotransferase \>2 \* upper limit of normal (ULN) at the screening visit. * Creatine phosphokinase \>3 \* ULN at the screening visit. The above information was not intended to contain all considerations relevant to a participants potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis | Baseline to Week 12 | Adjusted least square (LS) means and standard errors were obtained from the mixed model analysis with repeated measures (MMRM) to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 24 and 48 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on-or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis | Baseline to Week 12 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline on-treatment data from Week 4 to Week 48 (on-treatment Analysis). |
| Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted Percentage were obtained from a multiple imputation approach for handling of missing data including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
| Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Baseline, Weeks 12, 24 and 48 | 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). |
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Baseline to Weeks 12, 24 and 48 | Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. |
Countries
Brazil, Canada, Denmark, Mexico, Netherlands, Russia, Slovenia, Spain, Taiwan, Turkey (Türkiye)
Participant flow
Recruitment details
The study was conducted at 10 active centers (which screened at least 1 participant) in 10 countries worldwide. Overall, 20 participants were screened between 31 August 2018 and 4 January 2019, of whom 2 were screen failures. Of the 10 centers which screened participants, 9 centers enrolled at least 1 participant.
Pre-assignment details
A total of 18 participants were enrolled and received treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| Alirocumab 75 mg Q2W/up to 150 mg Q2W Participants with BW \<50 kg received SC injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW \>=50 kg. | 9 |
| Alirocumab 150 mg Q2W Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Alirocumab 75 mg Q2W/up to 150 mg Q2W | Alirocumab 150 mg Q2W | Total |
|---|---|---|---|
| Age, Continuous | 10.4 years STANDARD_DEVIATION 1.5 | 14.3 years STANDARD_DEVIATION 2.4 | 12.4 years STANDARD_DEVIATION 2.8 |
| Low-Density Lipoprotein Cholesterol (LDL-C) | 437.7 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 192.8 | 308.3 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 181.6 | 373.0 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 193.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 0 / 9 |
| other Total, other adverse events | 8 / 9 | 9 / 9 |
| serious Total, serious adverse events | 1 / 9 | 0 / 9 |
Outcome results
Primary
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis
Adjusted least square (LS) means and standard errors were obtained from the mixed model analysis with repeated measures (MMRM) to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis).
Time frame: Baseline to Week 12
Population: Analysis was performed on ITT population which included all enrolled participants who had received at least one dose or partial dose of alirocumab. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e. for combined population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis | -4.1 percent change | Standard Error 9 |
Secondary
Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | -33.4 mg/dL | Standard Error 19.1 |
| Alirocumab | Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | -43.0 mg/dL | Standard Error 19 |
| Alirocumab | Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | -15.0 mg/dL | Standard Error 25.7 |
Secondary
Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48
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 12, 24 and 48
Population: Analysis was performed on safety population which included participants who had received at least one dose or partial dose of alirocumab. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Baseline: Prepubescent | 3 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Baseline: Pubescent | 6 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Baseline: Post-pubescent | 0 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 12: Prepubescent | 3 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 12: Pubescent | 6 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 12: Post-pubescent | 0 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 24: Prepubescent | 2 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 24: Pubescent | 6 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 24: Post-pubescent | 0 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 48: Prepubescent | 1 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 48: Pubescent | 7 Participants |
| Alirocumab | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 48: Post-pubescent | 0 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 48: Pubescent | 7 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Baseline: Prepubescent | 0 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 24: Prepubescent | 0 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Baseline: Pubescent | 9 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 48: Prepubescent | 0 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Baseline: Post-pubescent | 0 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 24: Pubescent | 8 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 12: Prepubescent | 0 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 48: Post-pubescent | 2 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 12: Pubescent | 8 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 24: Post-pubescent | 1 Participants |
| Alirocumab 150 mg Q2W | Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48 | Week 12: Post-pubescent | 1 Participants |
Secondary
Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted Percentage were obtained from a multiple imputation approach for handling of missing data including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alirocumab | Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | 50.0 percentage of participants |
| Alirocumab | Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | 50.0 percentage of participants |
| Alirocumab | Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | 39.0 percentage of participants |
Secondary
Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data was planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | 11.3 percent change | Standard Error 6.9 |
| Alirocumab | Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | 14.6 percent change | Standard Error 6 |
| Alirocumab | Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | 11.3 percent change | Standard Error 5.8 |
Secondary
Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | -4.2 percent change | Standard Error 6.8 |
| Alirocumab | Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | -11.8 percent change | Standard Error 6.1 |
| Alirocumab | Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | 0.9 percent change | Standard Error 10.4 |
Secondary
Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | 2.8 percent change | Standard Error 8 |
| Alirocumab | Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | 5.2 percent change | Standard Error 16.2 |
| Alirocumab | Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | 10.0 percent change | Standard Error 8.2 |
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | 13.0 percent change | Standard Error 5.9 |
| Alirocumab | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | 8.9 percent change | Standard Error 4.4 |
| Alirocumab | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | 10.1 percent change | Standard Error 5.5 |
Secondary
Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on-or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | -5.2 percent change | Standard Error 8.1 |
| Alirocumab | Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | 7.4 percent change | Standard Error 7.6 |
| Alirocumab | Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | -6.4 percent change | Standard Error 12.2 |
Secondary
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline on-treatment data from Week 4 to Week 48 (on-treatment Analysis).
Time frame: Baseline to Week 12
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e. for combined population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis | -4.1 percent change | Standard Error 9 |
Secondary
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | -10.1 percent change | Standard Error 7.6 |
| Alirocumab | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | 4.2 percent change | Standard Error 12.8 |
Secondary
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis | Week 12 | -3.9 percent change | Standard Error 8.3 |
| Alirocumab | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis | Week 24 | -9.2 percent change | Standard Error 7.3 |
| Alirocumab | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis | Week 48 | 5.7 percent change | Standard Error 13.1 |
Secondary
Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.
Time frame: Baseline to Weeks 12, 24 and 48
Population: Analysis was performed on ITT population. As pre-specified, efficacy analysis data were planned to be collected and analyzed for all doses combined (i.e., for combined population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 12 | -1.9 percent change | Standard Error 7.2 |
| Alirocumab | Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 24 | -6.3 percent change | Standard Error 6.5 |
| Alirocumab | Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis | Week 48 | 5.5 percent change | Standard Error 10.7 |