Clinical trial NCT02624869: Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Familial Hypercholesterolemia
Keywords: Hypercholesterolemia
Elevated Cholesterol
High Cholesterol
PCSK9 mutations
Severe Familial Hypercholesterolemia
evolocumab
Repatha
Heterozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia
Pediatric
Paediatric
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-12-09
Enrollment: 163
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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:
measure: Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HeFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HoFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Non-HDL-C in HeFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Non-HDL-C in HoFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Apolipoprotein B in HeFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Apolipoprotein B in HoFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HeFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HoFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Apolipoprotein B / Apolipoprotein A1 Ratio in HeFH Participants
timeFrame: Baseline and week 80
measure: Percent Change From Baseline to Week 80 in Apolipoprotein B/Apolipoprotein A1 Ratio in HoFH Participants
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in LDL-C in HeFH Participants
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in LDL-C in HoFH Participants
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in Estradiol Levels
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in Testosterone Levels
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in Follicle Stimulating Hormone (FSH) Levels
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in Luteinizing Hormone (LH) Levels
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in Adenocorticotropic Hormone (ACTH) Levels
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in Dehydroepiandrosterone Sulfate (DHEA-S) Levels
timeFrame: Baseline and week 80
measure: Change From Baseline to Week 80 in Cortisol Levels
timeFrame: Baseline and week 80
measure: Number of Participants With Liver Function Test Abnormalities at Week 80
timeFrame: Week 80
measure: Number of Participants With Abnormalities in Levels of Creatine Kinase (CK) at Week 80
timeFrame: Week 80
measure: Change From Baseline to Week 80 in Carotid Intima-media Thickness (cIMT)
timeFrame: Baseline and week 80
measure: Change From Baseline in Height at Weeks 24, 48, and 80
timeFrame: Baseline and weeks 24, 48, and 80
measure: Change From Baseline in Weight at Weeks 24, 48, and 80
timeFrame: Baseline and weeks 24, 48, and 80
measure: Number of Participants With Change in Tanner Staging From Baseline to Week 80
timeFrame: Baseline and week 80
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Feldkirch
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: La Louvière
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
state: Ceará
city: Brasília
country: Brazil
facility: Research Site
state: Distrito Federal
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
state: Atlántico
city: Bucaramanga
country: Colombia
facility: Research Site
state: Santander
city: Svitavy
country: Czechia
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Kota Bharu
country: Malaysia
facility: Research Site
state: Kelantan
city: Amsterdam
country: Netherlands
facility: Research Site
city: Bergen
country: Norway
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Guimaraes
country: Portugal
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Ljubljana
country: Slovenia
facility: Research Site
city: Parktown
country: South Africa
facility: Research Site
state: Gauteng
city: Parow
country: South Africa
facility: Research Site
state: Western Cape
city: Cordoba
country: Spain
facility: Research Site
state: Andalucía
city: A Coruña
country: Spain
facility: Research Site
state: Galicia
city: Lugo
country: Spain
facility: Research Site
state: Galicia
city: Geneva 14
country: Switzerland
facility: Research Site
city: Reinach
country: Switzerland
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Santos RD, Ruzza A, Hovingh GK, Stefanutti C, Mach F, Descamps OS, Bergeron J, Wang B, Bartuli A, Buonuomo PS, Greber-Platzer S, Luirink I, Bhatia AK, Raal FJ, Kastelein JJP, Wiegman A, Gaudet D. Paediatric patients with heterozygous familial hypercholesterolaemia treated with evolocumab for 80 weeks (HAUSER-OLE): a single-arm, multicentre, open-label extension of HAUSER-RCT. Lancet Diabetes Endocrinol. 2022 Oct;10(10):732-740. doi: 10.1016/S2213-8587(22)00221-2. Epub 2022 Sep 5.
citation: Raal FJ, Hegele RA, Ruzza A, Lopez JAG, Bhatia AK, Wu J, Wang H, Gaudet D, Wiegman A, Wang J, Santos RD. Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies. Arterioscler Thromb Vasc Biol. 2024 May;44(5):1156-1164. doi: 10.1161/ATVBAHA.123.320268. Epub 2024 Mar 28.
citation: Santos RD, Ruzza A, Wang B, Maruff P, Schembri A, Bhatia AK, Mach F, Bergeron J, Gaudet I, St Pierre J, Kastelein JJP, Hovingh GK, Wiegman A, Gaudet D, Raal FJ. Evolocumab in paediatric heterozygous familial hypercholesterolaemia: cognitive function during 80 weeks of open-label extension treatment. Eur J Prev Cardiol. 2024 Feb 15;31(3):302-310. doi: 10.1093/eurjpc/zwad332.