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

Amgen158 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

158

Conditions

Heterozygous Familial Hypercholesterolemia

Interventions

EvolocumabDRUG

Dose of subcutaneous evolocumab every 4 weeks

PlaceboDRUG

Dose of subcutaneous placebo treatment every 4 weeks

Eligibility

Sex: ALLMin age: 10 YearsMax age: 17 Years

Medical Language ↔ Plain English

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) 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

Locations (66)

Outcomes

Primary Outcomes

Percent Change From Baseline to Week 24 in LDL-C

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.

Time frame: Baseline, Week 24

Secondary Outcomes

Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C

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.

Time frame: Baseline, Week 22, Week 24

Change From Baseline to Week 24 in LDL-C

Time frame: Baseline, Week 24

Percent Change From Baseline to Week 24 in Non-HDL-C

Time frame: Baseline, Week 24

Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)

Time frame: Baseline, Week 24

Data from ClinicalTrials.gov

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Research Site

Farmington, Connecticut, United States

Research Site

Wilmington, Delaware, United States

Research Site

Iowa City, Iowa, United States

Research Site

Towson, Maryland, United States

Research Site

Minneapolis, Minnesota, United States

Research Site

The Bronx, New York, United States

Research Site

Asheville, North Carolina, United States

Research Site

Cincinnati, Ohio, United States

Research Site

Pittsburgh, Pennsylvania, United States

Research Site

Nashville, Tennessee, United States

...and 56 more locations

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs

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.

Time frame: 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.