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.
Brief Title
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
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).
Categories
Completion Date
Completion Date Type
Actual
Conditions
Heterozygous Familial Hypercholesterolemia
Eligibility Criteria
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
* 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
Inclusion Criteria
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)
* 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)
Gender
All
Gender Based
false
Keywords
Hypercholesterolemia
Elevated Cholesterol
High Cholesterol
Heterozygous Familial Hypercholesterolemia
PCSK9 mutations
Paediatric
pediatric
Childhood Familial Hypercholesterolemia
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
NCT02392559
Org Class
Industry
Org Full Name
Amgen
Org Study Id
20120123
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Double-blind, Randomized, Multicenter, Placebo-Controlled Study to Characterize the Efficacy, Safety, and Tolerability of 24 Weeks of Evolocumab for LDL-C Reduction in Pediatric Subjects 10 to 17 Years of Age With HeFH
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percent Change From Baseline to Week 24 in LDL-C
Outcome Time Frame
Baseline, Week 24
Secondary Ids
Secondary Id
2014-002277-11
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Baseline, Week 22, Week 24
Outcome Measure
Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C
Outcome Description
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.
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Change From Baseline to Week 24 in LDL-C
Outcome Description
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
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline to Week 24 in Non-HDL-C
Outcome Description
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.
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)
Outcome Description
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.
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio
Outcome Description
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.
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio
Outcome Description
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.
Outcome 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.
Outcome Measure
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs
Outcome Description
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.
Outcome Time Frame
Week 24
Outcome Measure
Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3
Outcome Time Frame
Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Outcome Measure
Change From Baseline Over Time in Systolic Blood Pressure
Outcome Time Frame
Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Outcome Measure
Change From Baseline Over Time in Diastolic Blood Pressure
Outcome Time Frame
Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Outcome Measure
Change From Baseline Over Time in Heart Rate
Outcome Time Frame
up to Week 24
Outcome Measure
Number of Participants Testing Positive for Anti-Evolocumab Antibodies
Outcome Time Frame
Week 12, Week 22, Week 24
Outcome Measure
Serum Evolocumab Concentrations Over Time
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
Joseph Mahgerefteh
Investigator Email
jmahgere@montefiore.org
Investigator Phone
718-741-2343