An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT03510715
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Alirocumab Ezetimibe Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Simvastatin Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Alirocumab SAR236553 (REGN727) Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Fluvastatin Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Atorvastatin Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Pravastatin Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Lovastatin Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Rosuvastatin Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Fenofibrate Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Nicotinic acid Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Omega-3 fatty acids Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks. Alirocumab Cholestyramine Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (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 greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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 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.
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.
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 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 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.
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.
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.
Trial Locations
- Locations (10)
Investigational Site Number 2080001
🇩🇰Viborg, Denmark
Investigational Site Number 7240001
🇪🇸A Coruna, Spain
Investigational Site Number 7050001
🇸🇮Ljubljana, Slovenia
Investigational Site Number 4840006
🇲🇽Oaxaca, Mexico
Investigational Site Number 7920001
🇹🇷Izmir, Turkey
Investigational Site Number 1580001
🇨🇳Taipei, Taiwan
Investigational Site Number 5280001
🇳🇱Amsterdam, Netherlands
Investigational Site Number 1240001
🇨🇦Quebec, Canada
Investigational Site Number 0760001
🇧🇷Sao Paulo, Brazil
Investigational Site Number 6430002
🇷🇺Kemerovo, Russian Federation