Phase 3
N=153
An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Hypercholesterolaemia
Bottom Line
View on ClinicalTrials.gov: NCT03510884 ↗Enrolled (actual)
153
Serious AEs
5.7%
Results posted
May 2023
Primary outcome: Primary: DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand — 9.7; -33.6; -4.4; -38.2 percent change — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- 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 (Drug)
- Age
- Pediatric · 8+ yrs
- Sex
- All
- Sponsor
- Sanofi
- Primary completion
- Jan 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand |
9.7; -33.6; -4.4; -38.2 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand |
10.7; -34.8; 2.3; -39.2 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand |
10.4; -27.4; -3.6; -34.3 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand |
9.7; -31.0; -3.7; -35.6 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand |
7.4; -23.4; -4.4; -27.7 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand |
8.9; -30.0; 1.1; -31.7 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand |
9.8; -33.0; 2.8; -34.7 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand |
7.5; -25.3; 0.9; -27.0 | <0.0001 sig |
| SECONDARY DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand |
8.0; 73.3; 22.2; 76.3 | =0.0001 sig |
| SECONDARY DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand |
16.4; 70.6; 12.9; 72.6 | <0.0001 sig |
| SECONDARY DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand |
4.0; 57.2; 9.0; 67.2 | =0.0011 sig |
| SECONDARY DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand |
0.0; 61.2; 4.3; 57.0 | <0.0001 sig |
| SECONDARY DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand |
0.5; -14.7; 2.5; -22.4 | =0.0237 sig |
| SECONDARY DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand |
-7.1; -12.7; -2.5; -16.0 | =0.4288 |
| SECONDARY DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand |
-0.8; 5.6; -1.1; 3.4 | — |
| SECONDARY DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand |
7.7; 11.9; 12.2; -6.8 | — |
| SECONDARY DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand |
-0.1; 1.0; -4.5; 4.4 | — |
| SECONDARY DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand |
-2.2; 3.5; -3.5; 4.0 | — |
| SECONDARY DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand |
6.5; -2.2; 7.8; -0.3 | — |
| SECONDARY DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand |
-0.1; -1.7; -0.7; 5.0 | — |
| SECONDARY DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand |
10.7; -34.8; 2.3; -39.2; 9.7; -33.6 | — |
| SECONDARY DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand |
8.9; -30.0; 1.1; -31.7; 10.4; -27.4 | — |
| SECONDARY DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand |
9.8; -33.0; 2.8; -34.7; 9.7; -31.0 | — |
| SECONDARY DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand |
7.5; -25.3; 0.9; -27.0; 7.4; -23.4 | — |
| SECONDARY DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand |
16.4; 70.6; 12.9; 72.6; 8.0; 73.3 | — |
| SECONDARY DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand |
0.1; 61.7; 4.3; 57.0; 4.0; 57.2 | — |
| SECONDARY DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand |
-7.099; -12.746; -2.545; -16.042; 0.492; -14.748 | — |
| SECONDARY DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand |
-0.1; -1.7; -0.7; 5.0; -0.1; 1.0 | — |
| SECONDARY DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand |
-2.2; 3.5; -3.5; 4.0; -0.8; 5.6 | — |
| SECONDARY DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand |
6.5; -2.2; 7.8; -0.3; 7.7; 11.9 | — |
| SECONDARY DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand |
0.1; -0.2; 0.0; -0.3; 0.1; -0.2 | — |
| SECONDARY DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand |
0.1; -0.2; 0.0; -0.3; 0.1; -0.2 | — |
| SECONDARY DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand |
0.8; 65.8; 4.2; 70.8; 4.0; 66.7 | — |
| SECONDARY DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand |
0.8; 65.8; 4.2; 70.8; 4.0; 66.7 | — |
| SECONDARY DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand |
0.0; 25.2; 0.1; 31.9; 0.0; 21.6 | — |
| SECONDARY DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand |
0.0; 25.2; 0.1; 31.9; 0.0; 21.6 | — |
| SECONDARY DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand |
7.1; -35.4; -3.8; -42.0; 10.7; -34.8 | — |
| SECONDARY DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand |
7.1; -35.4; -3.8; -42.0; 10.7; -34.8 | — |
| SECONDARY OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand |
-23.3; -22.2; -27.1; -23.7 | — |
| SECONDARY OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand |
-22.8; -25.8; -27.6; -23.4 | — |
| SECONDARY Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104 |
-0.403; -0.313; -0.218; -0.136; -0.421; -0.334 | — |
| SECONDARY Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104 |
1; 4; 5; 0; 13; 13 | — |
| SECONDARY DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response |
0; 3; 0; 0; 0 | — |
Summary
Primary Objective:
To evaluate the efficacy of alirocumab administered every 2 weeks (Q2W) and every 4 weeks (Q4W) versus placebo after 24 weeks of double-blind (DB) treatment on low-density lipoprotein cholesterol (LDL-C) levels in participants with heterozygous familial hypercholesterolemia (heFH) 8 to 17 years of age on optimal stable daily dose of statin therapy ± other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins.
Secondary Objectives:
* To evaluate the efficacy of alirocumab versus placebo on LDL-C levels.
* To evaluate the effects of alirocumab versus placebo on other lipid parameters.
* To evaluate the safety and tolerability of alirocumab in comparison with placebo.
* To evaluate the efficacy, safety, and tolerability of alirocumab after open label treatment.
* To evaluate the development of anti-alirocumab antibodies.
Eligibility Criteria
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 ) 350 mg/dL (3.95 mmol/L).
- Severe renal impairment (ie, estimated glomerular filtration rate 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.
Data sourced from ClinicalTrials.gov (NCT03510884). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.