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.
Brief Title
Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Familial Hypercholesterolemia
Eligibility Criteria
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
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
Inclusion Criteria
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)
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)
Gender
All
Gender Based
false
Keywords
Hypercholesterolemia
Elevated Cholesterol
High Cholesterol
PCSK9 mutations
Severe Familial Hypercholesterolemia
evolocumab
Repatha
Heterozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia
Pediatric
Paediatric
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
10 Years
NCT Id
NCT02624869
Org Class
Industry
Org Full Name
Amgen
Org Study Id
20120124
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Open-label, Single-Arm, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Evolocumab for LDL-C Reduction, as Add-on to Diet and Lipid-lowering Therapy, in Pediatric Subjects From 10 to 17 Years of Age With Heterozygous Familial Hypercholesterolemia (HeFH) or Homozygous Familial Hypercholesterolemia (HoFH)
Primary Outcomes
Outcome Description
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.
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.
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Outcome 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 Ids
Secondary Id
2015-002276-25
Secondary Outcomes
Outcome Description
For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HeFH Participants
Outcome Description
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HoFH Participants
Outcome Description
For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Non-HDL-C in HeFH Participants
Outcome Description
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Non-HDL-C in HoFH Participants
Outcome Description
For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Apolipoprotein B in HeFH Participants
Outcome Description
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Apolipoprotein B in HoFH Participants
Outcome Description
For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HeFH Participants
Outcome Description
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HoFH Participants
Outcome Description
For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Apolipoprotein B / Apolipoprotein A1 Ratio in HeFH Participants
Outcome Description
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Percent Change From Baseline to Week 80 in Apolipoprotein B/Apolipoprotein A1 Ratio in HoFH Participants
Outcome Description
For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in LDL-C in HeFH Participants
Outcome Description
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in LDL-C in HoFH Participants
Outcome Description
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).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Estradiol Levels
Outcome Description
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).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Testosterone Levels
Outcome Description
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).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Follicle Stimulating Hormone (FSH) Levels
Outcome Description
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).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Luteinizing Hormone (LH) Levels
Outcome Description
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).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Adenocorticotropic Hormone (ACTH) Levels
Outcome Description
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).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Dehydroepiandrosterone Sulfate (DHEA-S) Levels
Outcome Description
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).
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Cortisol Levels
Outcome Description
Liver function tests included alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels and total bilirubin levels.
Outcome Time Frame
Week 80
Outcome Measure
Number of Participants With Liver Function Test Abnormalities at Week 80
Outcome Description
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.
Outcome Time Frame
Week 80
Outcome Measure
Number of Participants With Abnormalities in Levels of Creatine Kinase (CK) at Week 80
Outcome Description
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.
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.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Change From Baseline to Week 80 in Carotid Intima-media Thickness (cIMT)
Outcome Time Frame
Baseline and weeks 24, 48, and 80
Outcome Measure
Change From Baseline in Height at Weeks 24, 48, and 80
Outcome Time Frame
Baseline and weeks 24, 48, and 80
Outcome Measure
Change From Baseline in Weight at Weeks 24, 48, and 80
Outcome Description
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.
The number of participants with any change in Tanner Stage from baseline is reported.
Outcome Time Frame
Baseline and week 80
Outcome Measure
Number of Participants With Change in Tanner Staging From Baseline to Week 80
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
10
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nicole Sutton
Investigator Email
nsutton@montefiore.org
Investigator Phone
718-741-2343