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

Familial Hypercholesterolemia Clinical Trial

— HAUSER-OLE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02624869
• Other study ID #: 20120124
• Secondary ID: 2015-002276-25
• Status: Completed
• Phase: Phase 3
• Start date: September 10, 2016
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Biological:
• Evolocumab
Administered by subcutaneous injection

Locations

Country	Name	City	State
Australia	Research Site	Camperdown	New South Wales
Austria	Research Site	Feldkirch
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Gent
Belgium	Research Site	La Louvière
Belgium	Research Site	Leuven
Brazil	Research Site	Brasília	Distrito Federal
Brazil	Research Site	Fortaleza	Ceará
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Quebec
Colombia	Research Site	Barranquilla	Atlántico
Colombia	Research Site	Bucaramanga	Santander
Czechia	Research Site	Svitavy
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Italy	Research Site	Palermo
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Torino
Malaysia	Research Site	Kota Bharu	Kelantan
Netherlands	Research Site	Amsterdam
Norway	Research Site	Bergen
Norway	Research Site	Oslo
Poland	Research Site	Gdansk
Portugal	Research Site	Guimaraes
Russian Federation	Research Site	Saint Petersburg
Slovenia	Research Site	Ljubljana
South Africa	Research Site	Parktown	Gauteng
South Africa	Research Site	Parow	Western Cape
Spain	Research Site	A Coruña	Galicia
Spain	Research Site	Cordoba	Andalucía
Spain	Research Site	Lugo	Galicia
Switzerland	Research Site	Geneva 14
Switzerland	Research Site	Reinach
Turkey	Research Site	Ankara
Turkey	Research Site	Izmir
United Kingdom	Research Site	Birmingham
United States	Research Site	Bronx	New York
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Colombia,  Czechia,  Greece,  Hungary,  Italy,  Malaysia,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  Slovenia,  South Africa,  Spain,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

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

External Links

•   AmgenTrials clinical trials website