Clinical trial NCT02392559: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heterozygous Familial Hypercholesterolemia
Keywords: Hypercholesterolemia
Elevated Cholesterol
High Cholesterol
Heterozygous Familial Hypercholesterolemia
PCSK9 mutations
Paediatric
pediatric
Childhood Familial Hypercholesterolemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-03-19
Enrollment: 158
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

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

Primary outcomes:
measure: Percent Change From Baseline to Week 24 in LDL-C
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C
timeFrame: Baseline, Week 22, Week 24
measure: Change From Baseline to Week 24 in LDL-C
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline to Week 24 in Non-HDL-C
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio
timeFrame: Baseline, Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs
timeFrame: 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.
measure: Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3
timeFrame: Week 24
measure: Change From Baseline Over Time in Systolic Blood Pressure
timeFrame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
measure: Change From Baseline Over Time in Diastolic Blood Pressure
timeFrame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
measure: Change From Baseline Over Time in Heart Rate
timeFrame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
measure: Number of Participants Testing Positive for Anti-Evolocumab Antibodies
timeFrame: up to Week 24
measure: Serum Evolocumab Concentrations Over Time
timeFrame: Week 12, Week 22, Week 24
Other outcomes:
Locations:
city: Farmington
country: United States
facility: Research Site
state: Connecticut
city: Wilmington
country: United States
facility: Research Site
state: Delaware
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: Towson
country: United States
facility: Research Site
state: Maryland
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Bronx
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
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: Bruxelles
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: Vitória
country: Brazil
facility: Research Site
state: Espírito Santo
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: Floridablanca
country: Colombia
facility: Research Site
state: Santander
city: Ostrava-Poruba
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Svitavy
country: Czechia
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Kuopio
country: Finland
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: Christchurch
country: New Zealand
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: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Ljubljana
country: Slovenia
facility: Research Site
city: Pretoria
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: Sevilla
country: Spain
facility: Research Site
state: Andalucía
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
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: Taipei
country: Taiwan
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
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Santos RD, Ruzza A, Hovingh GK, Wiegman A, Mach F, Kurtz CE, Hamer A, Bridges I, Bartuli A, Bergeron J, Szamosi T, Santra S, Stefanutti C, Descamps OS, Greber-Platzer S, Luirink I, Kastelein JJP, Gaudet D; HAUSER-RCT Investigators. Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Oct 1;383(14):1317-1327. doi: 10.1056/NEJMoa2019910. Epub 2020 Aug 29.
citation: Gaudet D, Langslet G, Gidding SS, Luirink IK, Ruzza A, Kurtz C, Lu C, Somaratne R, Raal FJ, Wiegman A. Efficacy, safety, and tolerability of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia: Rationale and design of the HAUSER-RCT study. J Clin Lipidol. 2018 Sep-Oct;12(5):1199-1207. doi: 10.1016/j.jacl.2018.05.007. Epub 2018 May 22.
citation: Gaudet D, Ruzza A, Bridges I, Maruff P, Schembri A, Hamer A, Mach F, Bergeron J, Gaudet I, Pierre JS, Kastelein JJP, Hovingh GK, Wiegman A, Raal FJ, Santos RD. Cognitive function with evolocumab in pediatric heterozygous familial hypercholesterolemia. J Clin Lipidol. 2022 Sep-Oct;16(5):676-684. doi: 10.1016/j.jacl.2022.07.005. Epub 2022 Jul 21.
citation: Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.