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

Phase 3

Completed

Conditions: Familial Hypercholesterolemia

Interventions: Biological: Evolocumab

Registration Number: NCT02624869

Lead Sponsor: Amgen

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 163

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Evolocumab	Evolocumab	Participants receive 420 mg evolocumab administered by subcutaneous injection every 4 weeks (QM) for up to 80 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	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.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HoFH Participants	Baseline and week 80	For HoFH participants baseline was defined as the baseline value in this study (20120124).
Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HoFH Participants	Baseline and week 80	For HoFH participants baseline was defined as the baseline value in this study (20120124).
Change From Baseline to Week 80 in LDL-C in HeFH Participants	Baseline and week 80	For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Percent Change From Baseline to Week 80 in Non-HDL-C in HeFH Participants	Baseline and week 80	For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Number of Participants With Abnormalities in Levels of Creatine Kinase (CK) at Week 80	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.
Number of Participants With Change in Tanner Staging From Baseline to Week 80	Baseline and 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.
Change From Baseline to Week 80 in Cortisol Levels	Baseline and week 80	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).
Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HeFH Participants	Baseline and week 80	For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Percent Change From Baseline to Week 80 in Apolipoprotein B in HeFH Participants	Baseline and week 80	For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Percent Change From Baseline to Week 80 in Apolipoprotein B / Apolipoprotein A1 Ratio in HeFH Participants	Baseline and week 80	For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Percent Change From Baseline to Week 80 in Apolipoprotein B/Apolipoprotein A1 Ratio in HoFH Participants	Baseline and week 80	For HoFH participants baseline was defined as the baseline value in this study (20120124).
Change From Baseline to Week 80 in Testosterone Levels	Baseline and week 80	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).
Change From Baseline to Week 80 in Follicle Stimulating Hormone (FSH) Levels	Baseline and week 80	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).
Change From Baseline to Week 80 in Adenocorticotropic Hormone (ACTH) Levels	Baseline and week 80	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).
Percent Change From Baseline to Week 80 in Non-HDL-C in HoFH Participants	Baseline and week 80	For HoFH participants baseline was defined as the baseline value in this study (20120124).
Percent Change From Baseline to Week 80 in Apolipoprotein B in HoFH Participants	Baseline and week 80	For HoFH participants baseline was defined as the baseline value in this study (20120124).
Change From Baseline to Week 80 in LDL-C in HoFH Participants	Baseline and week 80	For HoFH participants baseline was defined as the baseline value in this study (20120124).
Change From Baseline in Height at Weeks 24, 48, and 80	Baseline and weeks 24, 48, and 80
Change From Baseline to Week 80 in Estradiol Levels	Baseline and week 80	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).
Change From Baseline to Week 80 in Luteinizing Hormone (LH) Levels	Baseline and week 80	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).
Change From Baseline to Week 80 in Dehydroepiandrosterone Sulfate (DHEA-S) Levels	Baseline and week 80	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).
Number of Participants With Liver Function Test Abnormalities at Week 80	Week 80	Liver function tests included alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels and total bilirubin levels.
Change From Baseline to Week 80 in Carotid Intima-media Thickness (cIMT)	Baseline and week 80	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.
Change From Baseline in Weight at Weeks 24, 48, and 80	Baseline and weeks 24, 48, and 80
Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HeFH Participants	Baseline and week 80	For HeFH participants baseline was defined as the baseline value in the parent study 20120123.