Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)

Amgen163 enrolled

Overview

The main purpose of this study is to describe the safety and tolerability of 80 weeks of subcutaneous (SC) evolocumab when added to standard of care in children 10 to 17 years of age with familial hypercholesterolemia.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

163

Conditions

Familial Hypercholesterolemia

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

Eligibility

Sex: ALLMin age: 10 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: Heterozygous Familial Hypercholesterolemia (HeFH): -Completed Study 20120123 (NCT02392559) while still on assigned investigational product and did not experience a treatment-related serious adverse event Homozygous Familial Hypercholesterolemia (HoFH): * Male or female, ≥ 10 to ≤ 17 years of age at time of enrollment * Diagnosis of HoFH * On a low-fat diet and receiving background lipid-lowering therapy * Lipid-lowering therapy unchanged for ≥ 4 weeks prior to LDL-C screening; fibrates must be stable for at least 6 weeks prior to screening. * Fasting LDL-C at screening ≥ 130 mg/dL (3.4 mmol/L) * Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) Exclusion Criteria: -Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s); except Study 20120123 HoFH: * Moderate to severe renal dysfunction * Active liver disease or hepatic dysfunction, * Creatine kinase \> 3 times the upper limit of normal (ULN) at screening

Locations (46)

Outcomes

Primary Outcomes

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event is defined as any untoward medical occurrence in a clinical trial participant, not necessarily having a causal relationship with study treatment. A serious AE is as an AE that met at least 1 of the following criteria: * fatal; * life threatening; * required in-patient hospitalization or prolongation of existing hospitalization; * resulted in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event. AEs were graded for severity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; urgent intervention indicated; Grade 5: Death related to AE.

Time frame: From first dose of evolocumab in this study up to and including 30 days after the last dose or up to the end of study date, whichever was earlier; up to 80 weeks.

Secondary Outcomes

Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HeFH Participants

For HeFH participants baseline was defined as the baseline value of the parent study 20120123.

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HoFH Participants

For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Non-HDL-C in HeFH Participants

For HeFH participants baseline was defined as the baseline value of the parent study 20120123.

Time frame: Baseline and week 80

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

The Bronx, New York, United States

Research Site

Cincinnati, Ohio, United States

Research Site

Nashville, Tennessee, United States

Research Site

Camperdown, New South Wales, Australia

Research Site

Feldkirch, Austria

Research Site

Salzburg, Austria

Research Site

Vienna, Austria

Research Site

Ghent, Belgium

Research Site

La Louvière, Belgium

Research Site

Leuven, Belgium

...and 36 more locations

Percent Change From Baseline to Week 80 in Non-HDL-C in HoFH Participants

For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Apolipoprotein B in HeFH Participants

For HeFH participants baseline was defined as the baseline value in the parent study 20120123.

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Apolipoprotein B in HoFH Participants

For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HeFH Participants

For HeFH participants baseline was defined as the baseline value in the parent study 20120123.

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HoFH Participants

For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Apolipoprotein B / Apolipoprotein A1 Ratio in HeFH Participants

For HeFH participants baseline was defined as the baseline value in the parent study 20120123.

Time frame: Baseline and week 80

Percent Change From Baseline to Week 80 in Apolipoprotein B/Apolipoprotein A1 Ratio in HoFH Participants

For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in LDL-C in HeFH Participants

For HeFH participants baseline was defined as the baseline value of the parent study 20120123.

Time frame: Baseline and week 80

Change From Baseline to Week 80 in LDL-C in HoFH Participants

For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in Estradiol Levels

For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in Testosterone Levels

For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in Follicle Stimulating Hormone (FSH) Levels

For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in Luteinizing Hormone (LH) Levels

For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in Adenocorticotropic Hormone (ACTH) Levels

For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in Dehydroepiandrosterone Sulfate (DHEA-S) Levels

For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Change From Baseline to Week 80 in Cortisol Levels

For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).

Time frame: Baseline and week 80

Number of Participants With Liver Function Test Abnormalities at Week 80

Liver function tests included alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels and total bilirubin levels.

Time frame: Week 80

Number of Participants With Abnormalities in Levels of Creatine Kinase (CK) at Week 80

The number of participants with levels of creatine kinase greater than 5 times the upper limit of normal (ULN) and greater than 10 times the ULN, measured by the central laboratory.

Time frame: Week 80

Change From Baseline to Week 80 in Carotid Intima-media Thickness (cIMT)

Carotid intima-media thickness measures the thickness of the intima and media, the inner two layers of the carotid artery, and is used to determine the extent of plaque buildup in the walls of the arteries (atherosclerosis) supplying blood to the head. CIMT was measured by ultrasonography and analyzed at a core laboratory. The largest values measured in the left common carotid artery (LCCA) and the right common carotid artery (RCCA) are averaged in this analysis.

Time frame: Baseline and week 80

Change From Baseline in Height at Weeks 24, 48, and 80

Time frame: Baseline and weeks 24, 48, and 80

Change From Baseline in Weight at Weeks 24, 48, and 80

Time frame: Baseline and weeks 24, 48, and 80

Number of Participants With Change in Tanner Staging From Baseline to Week 80

Pubertal growth and sexual maturity was assessed separately for males and females using the 5 Tanner stages where stage 1 = prepubertal and stage 5 = mature. The number of participants with any change in Tanner Stage from baseline is reported.

Time frame: Baseline and week 80