Trial Assessing Efficacy, Safety and Tolerability of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition in Paediatric Subjects With Genetic Low-Density Lipoprotein (LDL) Disorders

Phase 3

Completed

• Conditions: Heterozygous Familial Hypercholesterolemia
• Interventions: Drug: Placebo; Drug: Evolocumab

• Registration Number: NCT02392559
• Lead Sponsor: Amgen

Brief Summary

A study to assess safety and efficacy of evolocumab (AMG-145) in paediatric subjects aged 10-17 years diagnosed with heterozygous familial hypercholesterolemia.

Detailed Description

A study to evaluate the effect of 24 weeks of subcutaneous (SC) evolocumab compared with placebo, when added to standard of care, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in pediatric subjects 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH).

Study Timeline

• Study First Submitted: 2015-02-25
• Study First Submitted QC: 2015-03-13
• Study First Posted: 2015-03-19
• Study Start: 2016-03-24
• Primary Completion: 2019-11-25
• Study Completion: 2019-11-25
• Results First Submitted: 2020-06-09
• Results First Submitted QC: 2020-07-14
• Results First Posted: 2020-07-15
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-04
• Last Update Posted: 2022-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 158

Inclusion Criteria

• Male or female ≥ 10 to ≤ 17 years of age (before 18th birthday)
• Diagnosis of heterozygous familial hypercholesterolemia
• On an approved statin with stable optimized dose for ≥ 4 weeks
• Other lipid-lowering therapy stable for ≥ 4 weeks (fibrates must be stable for ≥ 6 weeks)
• Fasting LDL-C ≥ 130 mg/dL (3.4 mmol/L)
• Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

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Exclusion Criteria

• Type 1 diabetes, or type 2 diabetes that is or poorly controlled
• Uncontrolled hyperthyroidism or hypothyroidism
• Cholesterylester transfer protein (CETP) inhibitor in the last 12 months, or mipomersen or lomitapide in the last 5 months
• Previously received evolocumab or any other investigational therapy to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9).
• Lipid apheresis within the last 12 weeks prior to screening.
• Homozygous familial hypercholesterolemia

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching subcutaneous injection every 4 weeks (QM)
EvoMab 420 mg QM	Evolocumab	Evolocumab subcutaneous injection QM

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 24 in LDL-C	Baseline, Week 24	Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from interactive voice response system \[IVRS\]), scheduled visit and the interaction of treatment with scheduled visit as covariates. The model uses an unstructured covariance.

Secondary Outcome Measures

Name	Time	Method
Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C	Baseline, Week 22, Week 24	Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Change From Baseline to Week 24 in LDL-C	Baseline, Week 24	Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Change From Baseline Over Time in Heart Rate	Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio	Baseline, Week 24	Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Percent Change From Baseline to Week 24 in Non-HDL-C	Baseline, Week 24	Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates
Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)	Baseline, Week 24	Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio	Baseline, Week 24	Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3	Week 24	Laboratory toxicity grading was based on NCI CTCAE grading. Grade 3 indicates severe toxicity and Grade 4 indicates life-threatening toxicity. Values representing a worsening from baseline are shown.
Change From Baseline Over Time in Systolic Blood Pressure	Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Change From Baseline Over Time in Diastolic Blood Pressure	Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs	From first dose of study drug up to and including 30 days after the last dose or end of study date (Week 24), whichever was earlier. Mean (SD) duration on study was 5.664 (0.278) and 5.608 (0.137) months for Placebo and EvoMab arms, respectively.	An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. An SAE is defined as an adverse event that: is fatal; is a life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other medically important serious event. Events were graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading scale (1=mild; 2=moderate; 3=severe; 4=life-threatening; 5=death). Events were defined as treatment emergent if they occurred after the first dose of study drug and up to and including 30 days after the last dose or the end of study date, whichever is earlier.
Number of Participants Testing Positive for Anti-Evolocumab Antibodies	up to Week 24
Serum Evolocumab Concentrations Over Time	Week 12, Week 22, Week 24

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom