An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia

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.

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolaemia
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Alirocumab SAR236553 (REGN727); 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

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 Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1245AAM
    • Investigational Site Number :0320001
• Austria
  • Wien, Austria, 1090
    • Investigational Site Number :0400001
• Brazil
  • Sao Paulo, Brazil, 05403-900
    • Investigational Site Number :0760001
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Investigational Site Number :0760004
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Investigational Site Number :1000002
• Canada
  • Quebec, Canada, G1V 4W2
    • Investigational Site Number :1240001
• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number :2030002
  • Praha 5 - Motol, Czechia, 15006
    • Investigational Site Number :2030001
• Denmark
  • Copenhagen, Denmark, 2100
    • Investigational Site Number :2080001
• Finland
  • HUS, Finland, 00029
    • Investigational Site Number :2460001
• France
  • Bron, France, 69500
    • Investigational Site Number :2500001
  • Nantes, France, 44093
    • Investigational Site Number :2500002
• Hungary
  • Budapest, Hungary, 1094
    • Investigational Site Number :3480001
• Italy
  • Milano, Italy, 20142
    • Investigational Site Number :3800003
  • Palermo, Italy, 90127
    • Investigational Site Number :3800001
  • Roma, Italy
    • Investigational Site Number :3800002
• Lebanon
  • Beirut, Lebanon
    • Investigational Site Number :4220001
  • Room Hospital Street, Achrafie, Lebanon, 00000
    • Investigational Site Number :4220003
• Mexico
  • Oaxaca, Mexico, 68000
    • Investigational Site Number :4840007
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • Investigational Site Number :4840008
• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Investigational Site Number :5280001
• Norway
  • Oslo, Norway
    • Investigational Site Number :5780001
• Poland
  • Lodz, Poland, 93-338
    • Investigational Site Number :6160001
  • Pomorskie
    • Gdansk, Pomorskie, Poland
      • Investigational Site Number :6160002
• Russian Federation
  • Kazan, Russian Federation, 420138
    • Investigational Site Number :6430006
  • Kemerovo, Russian Federation, 650002
    • Investigational Site Number :6430001
  • Moscow, Russian Federation, 115446
    • Investigational Site Number :6430004
  • Ufa, Russian Federation, 450083
    • Investigational Site Number :6430002
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Investigational Site Number :7050001
• South Africa
  • Parow, South Africa, 7500
    • Investigational Site Number :7100002
• Spain
  • A Coruña, Spain, 15001
    • Investigational Site Number :7240002
  • Badalona, Spain, 08916
    • Investigational Site Number :7240004
  • Barcelona, Spain, 08208
    • Investigational Site Number :7240001
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Investigational Site Number :7240003
• Sweden
  • Stockholm, Sweden, 171 76
    • Investigational Site Number :7520001
• Taiwan
  • Taipei, Taiwan, 112
    • Investigational Site Number :1580001
• Turkey
  • Ankara, Turkey, 06500
    • Investigational Site Number :7920002
  • Izmir, Turkey, 35040
    • Investigational Site Number :7920001
• United States
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC-Site Number:8400001
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine-Site Number:8400006
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Presbyterian Novant Heart & Wellness-Site Number:8400002
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center-Site Number:8400005
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University-Site Number:8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Children and adolescent male and female participants 8 to 17 years of age at the time of signed informed consent.
• Participants with diagnosis of heFH through genotyping or clinical criteria.
• Participants treated with optimal dose of statin +/- other LMT(s) or non-statin LMT(s) if statin intolerant at stable dose for at least 4 weeks prior to screening lipid sampling.
• Participants with calculated LDL-C greater than or equal to 130 mg/dL (>=3.37 mmol/L) at the screening visit except for participants who have previously participated in the DFI14223 (NCT02890992) study.
• A signed informed consent indicating parental permission with or without participant assent.

Exclusion criteria:

• Participant with body weight < 25 kg.
• Participants aged of 8 to 9 years not at Tanner stage 1 and participants aged of 10 to 17 years not at least at Tanner stage 2 in their development.
• Participants with secondary hyperlipidemia.
• Diagnosis of homozygous familial hypercholesterolemia.
• Participant who had received lipid apheresis treatment within 2 months prior to the screening period, or has plans to receive it during the study.
• Participants with uncontrolled type 1 or type 2 diabetes mellitus.
• Participants with known uncontrolled thyroid disease.
• Participants with uncontrolled hypertension.
• Fasting triglycerides greater than (>) 350 mg/dL (3.95 mmol/L).
• Severe renal impairment (ie, estimated glomerular filtration rate <30 mL/min/1.73 m^2).
• Alanine aminotransferase or aspartate aminotransferase >2*upper limit of normal (ULN).
• Creatinine phosphokinase (CPK) >3*ULN.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo/Alirocumab Q2W; 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).	Drug: Rosuvastatin; Pharmaceutical form:tablet Route of administration: oral; Drug: Alirocumab SAR236553 (REGN727); Pharmaceutical form:solution Route of administration: subcutaneous injection; Other Names: Praluent; Drug: Atorvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Simvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Pravastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Lovastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fluvastatin; Pharmaceutical form:Capsule Route of administration: Oral; Drug: Ezetimibe; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Cholestyramine; Pharmaceutical form:oral suspension Route of administration: oral; Drug: Nicotinic acid; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fenofibrate; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Omega-3 fatty acids; Pharmaceutical form:capsule Route of administration: oral; Drug: Placebo; Pharmaceutical form:solution Route of administration: subcutaneous injection
Experimental: Alirocumab Q2W; Participants received SC injection of alirocumab 40 mg (for BW <50 kg) or 75 mg (for BW >=50 kg) Q2W for 24 weeks in DB treatment period 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).	Drug: Rosuvastatin; Pharmaceutical form:tablet Route of administration: oral; Drug: Alirocumab SAR236553 (REGN727); Pharmaceutical form:solution Route of administration: subcutaneous injection; Other Names: Praluent; Drug: Atorvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Simvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Pravastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Lovastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fluvastatin; Pharmaceutical form:Capsule Route of administration: Oral; Drug: Ezetimibe; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Cholestyramine; Pharmaceutical form:oral suspension Route of administration: oral; Drug: Nicotinic acid; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fenofibrate; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Omega-3 fatty acids; Pharmaceutical form:capsule Route of administration: oral
Experimental: Placebo/Alirocumab Q4W; Participants received SC injection of placebo (matched to alirocumab) based on their BW (<50 kg or >=50 kg) Q4W for 24 weeks in DB treatment period 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).	Drug: Rosuvastatin; Pharmaceutical form:tablet Route of administration: oral; Drug: Alirocumab SAR236553 (REGN727); Pharmaceutical form:solution Route of administration: subcutaneous injection; Other Names: Praluent; Drug: Atorvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Simvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Pravastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Lovastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fluvastatin; Pharmaceutical form:Capsule Route of administration: Oral; Drug: Ezetimibe; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Cholestyramine; Pharmaceutical form:oral suspension Route of administration: oral; Drug: Nicotinic acid; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fenofibrate; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Omega-3 fatty acids; Pharmaceutical form:capsule Route of administration: oral; Drug: Placebo; Pharmaceutical form:solution Route of administration: subcutaneous injection
Experimental: Alirocumab Q4W; Participants received SC injection of alirocumab 150 mg (for BW <50 kg) or 300 mg (for BW >=50 kg) Q4W for 24 weeks in DB treatment period 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).	Drug: Rosuvastatin; Pharmaceutical form:tablet Route of administration: oral; Drug: Alirocumab SAR236553 (REGN727); Pharmaceutical form:solution Route of administration: subcutaneous injection; Other Names: Praluent; Drug: Atorvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Simvastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Pravastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Lovastatin; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fluvastatin; Pharmaceutical form:Capsule Route of administration: Oral; Drug: Ezetimibe; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Cholestyramine; Pharmaceutical form:oral suspension Route of administration: oral; Drug: Nicotinic acid; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Fenofibrate; Pharmaceutical form:Tablet Route of administration: Oral; Drug: Omega-3 fatty acids; Pharmaceutical form:capsule Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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).	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.	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): August 5, 2022

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 27, 2018

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Vitamins; Vitamin B Complex; Atorvastatin; Rosuvastatin Calcium; Pravastatin; Nicotinic Acids; Simvastatin; Fenofibrate; Niacinamide; Niacin; Ezetimibe; Lovastatin; Cholestyramine Resin
• Other Study ID Numbers: EFC14643; 2017-001903-60 (EudraCT Number); U1111-1193-0721 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No