HypercholesterolaemiaPhase 3NCT03510884
An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
A Phase 3 study testing Alirocumab SAR236553 (REGN727), Rosuvastatin and Atorvastatin in people with Hypercholesterolaemia, run by Sanofi at 43 sites in 24 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Hypercholesterolaemia
- What is being tested?
- Alirocumab SAR236553 (REGN727), Rosuvastatin and Atorvastatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 153 participants
- Where
- 43 sitesin 24 countries
- Study dates
- 31 May 2018to 5 Aug 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
43 sites in 24 countries.
43 sites in 24 countries
United States5 sites
Excel Medical Clinical Trials, LLC-Site Number:8400001
Boca Raton, Florida, 33434
Presbyterian Novant Heart & Wellness-Site Number:8400002
Charlotte, North Carolina, 28204
Cincinnati Children's Hospital Medical Center-Site Number:8400005
Cincinnati, Ohio, 45229
Vanderbilt University-Site Number:8400003
Nashville, Tennessee, 37232
Washington University School of Medicine-Site Number:8400006
St Louis, Missouri, 63110
Russia4 sites
Investigational Site Number :6430006
Kazan', 420138
Investigational Site Number :6430001
Kemerovo, 650002
Investigational Site Number :6430004
Moscow, 115446
Investigational Site Number :6430002
Ufa, 450083
Spain4 sites
Investigational Site Number :7240002
A Coruña, 15001
Investigational Site Number :7240004
Badalona, 08916
Investigational Site Number :7240001
Barcelona, 08208
Investigational Site Number :7240003
Pamplona, Navarre, 31008
Italy3 sites
Investigational Site Number :3800003
Milan, 20142
Investigational Site Number :3800001
Palermo, 90127
Investigational Site Number :3800002
Roma
Brazil2 sites
Investigational Site Number :0760004
Porto Alegre, Rio Grande do Sul, 91350-200
Investigational Site Number :0760001
São Paulo, 05403-900
Czechia2 sites
Investigational Site Number :2030002
Brno, 62500
Investigational Site Number :2030001
Praha 5 - Motol, 15006
France2 sites
Investigational Site Number :2500001
Bron, 69500
Investigational Site Number :2500002
Nantes, 44093
Lebanon2 sites
Investigational Site Number :4220001
Beirut
Investigational Site Number :4220003
Room Hospital Street, Achrafie, 00000
Mexico2 sites
Investigational Site Number :4840008
Guadalajara, Jalisco, 44100
Investigational Site Number :4840007
Oaxaca City, 68000
Poland2 sites
Investigational Site Number :6160002
Gdansk, Pomeranian Voivodeship
Investigational Site Number :6160001
Lodz, 93-338
Turkey (Türkiye)2 sites
Investigational Site Number :7920002
Ankara, 06500
Investigational Site Number :7920001
Izmir, 35040
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study Followed by an Open Label Treatment Period to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
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.
Read more
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.
Read the 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).
- Conditions
- Hypercholesterolaemia
- Being tested
- Alirocumab SAR236553 (REGN727), Rosuvastatin, Atorvastatin, Simvastatin, Pravastatin
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alirocumab SAR236553 (REGN727)Drug
Also called Praluent
Pharmaceutical form:solution Route of administration: subcutaneous injection
RosuvastatinDrug
Pharmaceutical form:tablet Route of administration: oral
AtorvastatinDrug
Pharmaceutical form:Tablet Route of administration: Oral
SimvastatinDrug
Pharmaceutical form:Tablet Route of administration: Oral
PravastatinDrug
Pharmaceutical form:Tablet Route of administration: Oral
LovastatinDrug
Pharmaceutical form:Tablet Route of administration: Oral
FluvastatinDrug
Pharmaceutical form:Capsule Route of administration: Oral
EzetimibeDrug
Pharmaceutical form:Tablet Route of administration: Oral
CholestyramineDrug
Pharmaceutical form:oral suspension Route of administration: oral
Nicotinic acidDrug
Pharmaceutical form:Tablet Route of administration: Oral
FenofibrateDrug
Pharmaceutical form:Tablet Route of administration: Oral
Omega-3 fatty acidsDrug
Pharmaceutical form:capsule Route of administration: oral
PlaceboDrug
Pharmaceutical form:solution Route of administration: subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Placebo/Alirocumab Q2W | Experimental | Participants received subcutaneous (SC) injection of placebo (matched to alirocumab) based on their body weight (BW) (less than [<] 50 kilograms [kg] or greater than or equal to [>=] 50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 milligrams (mg) (for BW <50 kg) or 75 mg (for BW >=50 kg) Q2W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW <50 kg) or 75 mg to 150 mg (for BW >=50 kg) or down titrated as 75 mg to 40 mg (for BW <50 kg) or 150 mg to 75 mg (for BW >=50 kg). Receives: Drug: Alirocumab SAR236553 (REGN727); Drug: Rosuvastatin; Drug: Atorvastatin; Drug: Simvastatin; Drug: Pravastatin; Drug: Lovastatin; Drug: Fluvastatin; Drug: Ezetimibe; Drug: Cholestyramine; Drug: Nicotinic acid; Drug: Fenofibrate; Drug: Omega-3 fatty acids; Drug: Placebo |
| Alirocumab Q2W | Experimental | 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 added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level was >=110 milligrams per deciliter (mg/dL) (2.85 millimoles per liter [mmol/L]) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 mg (for BW <50 kg) or 75 mg (for BW >=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW <50 kg) or 75 mg to 150 mg (for BW >=50 kg) or down titrated as 75 mg to 40 mg (for BW <50 kg) or 150 mg to 75 mg (for BW >=50 kg). Receives: Drug: Alirocumab SAR236553 (REGN727); Drug: Rosuvastatin; Drug: Atorvastatin; Drug: Simvastatin; Drug: Pravastatin; Drug: Lovastatin; Drug: Fluvastatin; Drug: Ezetimibe; Drug: Cholestyramine; Drug: Nicotinic acid; Drug: Fenofibrate; Drug: Omega-3 fatty acids |
| Placebo/Alirocumab Q4W | Experimental | 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 added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) Q4W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW <50 kg) or 300 mg Q4W to 150 mg Q2W (for BW >=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW <50 kg) or 150 mg Q2W to 75 mg Q2W (for BW >=50 kg). Receives: Drug: Alirocumab SAR236553 (REGN727); Drug: Rosuvastatin; Drug: Atorvastatin; Drug: Simvastatin; Drug: Pravastatin; Drug: Lovastatin; Drug: Fluvastatin; Drug: Ezetimibe; Drug: Cholestyramine; Drug: Nicotinic acid; Drug: Fenofibrate; Drug: Omega-3 fatty acids; Drug: Placebo |
| Alirocumab Q4W | Experimental | 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 added to stable 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. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW <50 kg) or 300 mg Q4W to 150 mg Q2W (for BW >=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW <50 kg) or 150 mg Q2W to 75 mg Q2W (for BW >=50 kg). Receives: Drug: Alirocumab SAR236553 (REGN727); Drug: Rosuvastatin; Drug: Atorvastatin; Drug: Simvastatin; Drug: Pravastatin; Drug: Lovastatin; Drug: Fluvastatin; Drug: Ezetimibe; Drug: Cholestyramine; Drug: Nicotinic acid; Drug: Fenofibrate; Drug: Omega-3 fatty acids |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 24
Secondary outcomes (42)
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: At Week 24
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.
Measured: At Week 12
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.
Measured: At Week 24
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.
Measured: At Week 12
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Weeks 12, and 24
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.
Measured: Baseline, Weeks 12 and 24
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.
Measured: Baseline, Weeks 12 and 24
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.
Measured: Baseline, Weeks 12 and 24
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.
Measured: Weeks 12 and 24
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.
Measured: Weeks 12 and 24
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.
Measured: Baseline, Weeks 12 and 24
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.
Measured: Baseline, Weeks 12 and 24
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.
Measured: Baseline, Weeks 12, and 24
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.
Measured: Baseline, Weeks 12, and 24
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.
Measured: Baseline, Weeks 12, and 24
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.
Measured: Baseline, Weeks 12, and 24
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.
Measured: At Weeks 12 and 24
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.
Measured: At Weeks 12 and 24
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.
Measured: At Weeks 12 and 24
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.
Measured: At Weeks 12 and 24
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.
Measured: Baseline to Weeks 8, 12 and 24
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.
Measured: Baseline to Weeks 8, 12 and 24
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.
Measured: Baseline, Week 104
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.
Measured: Baseline, Week 104
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.
Measured: Baseline, Weeks 24, 68 and 104
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).
Measured: Baseline, Weeks 24, 68 and 104
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.
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2018
- Study start31 May 2018
- Primary completion14 Jan 2021
- Study completion5 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolaemiaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03510884
- Sponsor's protocol ID
- EFC14643
- Other IDs
- 2017-001903-60, U1111-1193-0721, 2017
- Status last verified
- Apr 2023
- First submitted
- 18 Apr 2018
- Last updated
- 6 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Santos RD, Wiegman A, Caprio S, Cariou B, Averna M, Poulouin Y, Scemama M, Manvelian G, Garon G, Daniels S. Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA Pediatr. 2024 Mar 1;178(3):283-293. doi: 10.1001/jamapediatrics.2023.6477.
PubMed 38315470
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study Followed by an Open Label Treatment Period to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT03510884
- Acronym / sponsor ID
- EFC14643
- Conditions
- Hypercholesterolaemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 31 May 2018 (actual)
- Primary completion
- 14 Jan 2021 (actual)
- Study completion
- 5 Aug 2022 (actual)
- First posted
- 27 Apr 2018 (actual)
- Results
- Posted 6 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo/Alirocumab Q2W | Experimental | Drug: Alirocumab SAR236553 (REGN727), Drug: Rosuvastatin, Drug: Atorvastatin, Drug: Simvastatin, Drug: Pravastatin, Drug: Lovastatin, Drug: Fluvastatin, Drug: Ezetimibe, Drug: Cholestyramine, Drug: Nicotinic acid, Drug: Fenofibrate, Drug: Omega-3 fatty acids, Drug: PlaceboParticipants received subcutaneous (SC) injection of placebo (matched to alirocumab) based on their body weight (BW) (less than [<] 50 kilograms [kg] or greater than or equal to [>=] 50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 milligrams (mg) (for BW <50 kg) or 75 mg (for BW >=50 kg) Q2W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW <50 kg) or 75 mg to 150 mg (for BW >=50 kg) or down titrated as 75 mg to 40 mg (for BW <50 kg) or 150 mg to 75 mg (for BW >=50 kg). |
| Alirocumab Q2W | Experimental | Drug: Alirocumab SAR236553 (REGN727), Drug: Rosuvastatin, Drug: Atorvastatin, Drug: Simvastatin, Drug: Pravastatin, Drug: Lovastatin, Drug: Fluvastatin, Drug: Ezetimibe, Drug: Cholestyramine, Drug: Nicotinic acid, Drug: Fenofibrate, Drug: Omega-3 fatty acidsParticipants 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 added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level was >=110 milligrams per deciliter (mg/dL) (2.85 millimoles per liter [mmol/L]) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 mg (for BW <50 kg) or 75 mg (for BW >=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW <50 kg) or 75 mg to 150 mg (for BW >=50 kg) or down titrated as 75 mg to 40 mg (for BW <50 kg) or 150 mg to 75 mg (for BW >=50 kg). |
| Placebo/Alirocumab Q4W | Experimental | Drug: Alirocumab SAR236553 (REGN727), Drug: Rosuvastatin, Drug: Atorvastatin, Drug: Simvastatin, Drug: Pravastatin, Drug: Lovastatin, Drug: Fluvastatin, Drug: Ezetimibe, Drug: Cholestyramine, Drug: Nicotinic acid, Drug: Fenofibrate, Drug: Omega-3 fatty acids, Drug: PlaceboParticipants 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 added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) Q4W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW <50 kg) or 300 mg Q4W to 150 mg Q2W (for BW >=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW <50 kg) or 150 mg Q2W to 75 mg Q2W (for BW >=50 kg). |
| Alirocumab Q4W | Experimental | Drug: Alirocumab SAR236553 (REGN727), Drug: Rosuvastatin, Drug: Atorvastatin, Drug: Simvastatin, Drug: Pravastatin, Drug: Lovastatin, Drug: Fluvastatin, Drug: Ezetimibe, Drug: Cholestyramine, Drug: Nicotinic acid, Drug: Fenofibrate, Drug: Omega-3 fatty acidsParticipants 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 added to stable 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. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from <50 kg to >=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW <50 kg) or 300 mg Q4W to 150 mg Q2W (for BW >=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW <50 kg) or 150 mg Q2W to 75 mg Q2W (for BW >=50 kg). |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alirocumab SAR236553 (REGN727)Also: PraluentPharmaceutical form:solution Route of administration: subcutaneous injection | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| RosuvastatinPharmaceutical form:tablet Route of administration: oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| AtorvastatinPharmaceutical form:Tablet Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| SimvastatinPharmaceutical form:Tablet Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| PravastatinPharmaceutical form:Tablet Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| LovastatinPharmaceutical form:Tablet Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| FluvastatinPharmaceutical form:Capsule Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| EzetimibePharmaceutical form:Tablet Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| CholestyraminePharmaceutical form:oral suspension Route of administration: oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| Nicotinic acidPharmaceutical form:Tablet Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| FenofibratePharmaceutical form:Tablet Route of administration: Oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| Omega-3 fatty acidsPharmaceutical form:capsule Route of administration: oral | Drug | Alirocumab Q2W, Alirocumab Q4W, Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
| PlaceboPharmaceutical form:solution Route of administration: subcutaneous injection | Drug | Placebo/Alirocumab Q2W, Placebo/Alirocumab Q4W |
Primary outcome
DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand
Time frame: 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.
42 secondary outcomes
DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand
Time frame: Baseline, Week 12
DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand
Time frame: Baseline, Week 24
DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand
Time frame: Baseline, Week 24
DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand
Time frame: Baseline, Week 24
DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand
Time frame: Baseline, Week 12
DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand
Time frame: Baseline, Week 12
DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand
Time frame: Baseline, Week 12
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
Time frame: At Week 24
DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand
Time frame: At Week 12
DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand
Time frame: At Week 24
DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand
Time frame: At Week 12
DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand
Time frame: Baseline, Week 24
DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand
Time frame: Baseline, Week 12
DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand
Time frame: Baseline, Week 24
DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand
Time frame: Baseline, Week 24
DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand
Time frame: Baseline, Week 24
DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand
Time frame: Baseline, Week 12
DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand
Time frame: Baseline, Week 12
DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand
Time frame: Baseline, Week 12
DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12, and 24
DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12 and 24
DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12 and 24
DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12 and 24
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
Time frame: Weeks 12 and 24
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
Time frame: Weeks 12 and 24
DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12 and 24
DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12 and 24
DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12, and 24
DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12, and 24
DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand
Time frame: Baseline, Weeks 12, and 24
DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand
Time frame: Baseline, Weeks 12, and 24
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
Time frame: At Weeks 12 and 24
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
Time frame: At Weeks 12 and 24
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
Time frame: At Weeks 12 and 24
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
Time frame: At Weeks 12 and 24
DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand
Time frame: Baseline to Weeks 8, 12 and 24
DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand
Time frame: Baseline to Weeks 8, 12 and 24
OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand
Time frame: Baseline, Week 104
OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand
Time frame: Baseline, Week 104
Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104
Time frame: Baseline, Weeks 24, 68 and 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38315470Santos RD, Wiegman A, Caprio S, Cariou B, Averna M, Poulouin Y, Scemama M, Manvelian G, Garon G, Daniels S. Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA Pediatr. 2024 Mar 1;178(3):283-293. doi: 10.1001/jamapediatrics.2023.6477.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
43 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alirocumab SAR236553 (REGN727), Rosuvastatin and Atorvastatin in people with Hypercholesterolaemia, run by Sanofi at 43 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Russia, Spain, Italy, Brazil and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03510884, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.