Phase 2
N=42
An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Hypercholesterolaemia
Bottom Line
View on ClinicalTrials.gov: NCT02890992 ↗Enrolled (actual)
42
Serious AEs
0.0%
Results posted
Sep 2019
Primary outcome: Primary: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 — -41.1; -7.9; -40.6; -49.8 percent change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- alirocumab SAR236553 (REGN727) (Drug); statins (Drug); ezetimibe (Drug); cholestyramine (Drug); fenofibrate (Drug); omega-3 fatty acids (Drug); nicotinic acid (Drug)
- Age
- Pediatric · 8+ yrs
- Sex
- All
- Sponsor
- Sanofi
- Primary completion
- Sep 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 |
-41.1; -7.9; -40.6; -49.8; -17.5; 4.0 | — |
| SECONDARY Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 |
-83.7; -27.6; -55.5; -88.3; -32.4; 0.1 | — |
| SECONDARY Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 |
100.0; 33.3; 97.6; 83.0; 33.3; 20.0 | — |
| SECONDARY Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 |
0.0; 0.0; 93.4; 65.7; 16.7; 20.0 | — |
| SECONDARY Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4 |
-29.7; -49.2 | — |
| SECONDARY Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 |
-38.4; -9.7; -36.4; -40.1; -12.6; -0.9 | — |
| SECONDARY Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 |
-39.6; -7.1; -39.7; -43.9; -14.4; 3.2 | — |
| SECONDARY Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 |
-29.0; -4.1; -28.6; -34.2; -10.7; 5.2 | — |
| SECONDARY Percent Change From Baseline in Lipoprotein(a) at Week 8 |
4.5; -26.9; 1.5; -25.2; 2.2; -7.7 | — |
| SECONDARY Percent Change From Baseline in Fasting Triglyceride at Week 8 |
-0.4; -4.0; -7.4; 14.5; 19.3; -3.1 | — |
| SECONDARY Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 |
9.7; 16.5; 14.7; 10.6; 5.2; 13.8 | — |
| SECONDARY Percent Change From Baseline in Apolipoprotein A-1 at Week 8 |
4.4; 14.8; 10.7; 1.8; 8.9; 7.4 | — |
| SECONDARY Absolute Change From Baseline in Apolipoprotein B at Week 8 |
-51.7; -18.5; -35.3; -53.4; -15.3; -5.4 | — |
| SECONDARY Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 |
-86.1; -28.7; -62.7; -88.5; -29.5; -0.6 | — |
| SECONDARY Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 |
-80.1; -20.8; -57.1; -84.4; -27.2; 5.3 | — |
| SECONDARY Absolute Change From Baseline in Lipoprotein(a) at Week 8 |
0.003; -0.021; 0.007; -0.025; 0.023; -0.031 | — |
| SECONDARY Absolute Change From Baseline in HDL-C at Week 8 |
5.9; 7.7; 5.5; 4.9; 2.4; 5.9 | — |
| SECONDARY Absolute Change From Baseline in Fasting Triglyceride at Week 8 |
-0.121; -0.076; 0.168; 0.111; 0.117; -0.045 | — |
| SECONDARY Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 |
4.0; 17.7; 11.3; -0.4; 10.5; 8.0 | — |
| SECONDARY Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 |
-0.363; -0.262; -0.370; -0.402; -0.190; -0.086 | — |
Summary
Primary Objective:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) participants aged of 8 to 17 years, with LDL-C >=130 milligrams per deciliter (mg/dL) (3.37 millimoles per litre [mmol/L]) 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 for at least 4 weeks prior to the screening period.
Secondary Objective:
* To evaluate the safety and tolerability of alirocumab.
* To evaluate the pharmacokinetics profile of alirocumab.
* To evaluate the effects of alirocumab on other lipid parameters.
Eligibility Criteria
Inclusion criteria
- Children and adolescent male and female participants aged of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female participants aged >=12 and =3.37 mmol/L) at the screening visit.
- Participants with body weight greater than or equal to 25 kg.
- Participants aged of 8 to 9 years to be at Tanner stage 1 and participants aged of 10 to 17 years to be at least at Tanner stage 2 in their development.
- A signed informed consent indicating parental permission with or without participant assent.
Exclusion criteria
- Participant 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.
- Known history of type 1 or type 2 diabetes mellitus.
- Known history of thyroid disease.
- Known history of hypertension.
- Fasting triglycerides >350 mg/dL (3.95 mmol/L).
- Severe renal impairment (i.e., estimated glomerular filtration rate [eGFR] 2 x upper limit of normal (ULN).
- Creatinine phosphokinase (CPK) >3 x ULN.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT02890992). 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.