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

NCT02624869 | Completed Phase 3 Results DMC

• 2 other identifiers: 201201242015-002276-25
• Study Type: interventional
• Target: 163
• Locations: 22 countries
• Sites: 45

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.

Conditions

Familial Hypercholesterolemia

Keywords

Hypercholesterolemia; Elevated Cholesterol; High Cholesterol; PCSK9 mutations; Severe Familial Hypercholesterolemia; evolocumab; Repatha; Heterozygous Familial Hypercholesterolemia; Homozygous Familial Hypercholesterolemia; Pediatric; Paediatric

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HeFH Participants

  Baseline and week 80

• Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HoFH Participants

  Baseline and week 80

• Percent Change From Baseline to Week 80 in Non-HDL-C in HeFH Participants

  Baseline and week 80

• Percent Change From Baseline to Week 80 in Non-HDL-C in HoFH Participants

  Baseline and week 80

• Percent Change From Baseline to Week 80 in Apolipoprotein B in HeFH Participants

  Baseline and week 80

Study Arms (1)

Evolocumab

EXPERIMENTAL

Participants receive 420 mg evolocumab administered by subcutaneous injection every 4 weeks (QM) for up to 80 weeks.

Biological: Evolocumab

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: Repatha®, AMG 145

Evolocumab

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (46)

Research Site

The Bronx, New York, 10467, United States

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Cincinnati, Ohio, 45227, United States

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Nashville, Tennessee, 37212, United States

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Camperdown, New South Wales, 2050, Australia

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Feldkirch, 6800, Austria

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Salzburg, 5020, Austria

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Vienna, 1090, Austria

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Ghent, 9000, Belgium

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La Louvière, 7100, Belgium

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Leuven, 3000, Belgium

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Fortaleza, Ceará, 60430-270, Brazil

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Brasília, Federal District, 71625-175, Brazil

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São Paulo, 04040-000, Brazil

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São Paulo, 05403-000, Brazil

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Chicoutimi, Quebec, G7H 5H6, Canada

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Chicoutimi, Quebec, G7H 7K9, Canada

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Québec, Quebec, G1V 4W2, Canada

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Barranquilla, Atlántico, 080020, Colombia

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Bucaramanga, Santander Department, 81004, Colombia

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Svitavy, 568 25, Czechia

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Athens, 17674, Greece

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Thessaloniki, 54642, Greece

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Budapest, 1094, Hungary

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Palermo, 90127, Italy

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Pisa, 56124, Italy

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Roma, 00161, Italy

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Roma, 00165, Italy

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Torino, 10126, Italy

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Kota Bharu, Kelantan, 16150, Malaysia

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Amsterdam, 1066 EC, Netherlands

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Bergen, 5021, Norway

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Oslo, 0586, Norway

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Gdansk, 80-952, Poland

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Guimarães, 4835-044, Portugal

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Saint Petersburg, 191025, Russia

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Ljubljana, 1000, Slovenia

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Parktown, Gauteng, 2193, South Africa

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Parow, Western Cape, 7505, South Africa

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Córdoba, Andalusia, 14004, Spain

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A Coruña, Galicia, 15001, Spain

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Lugo, Galicia, 27003, Spain

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Geneva, 1211, Switzerland

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Reinach, 4153, Switzerland

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Ankara, 06500, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Birmingham, B4 6NH, United Kingdom

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Related Publications (3)

• 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.

  PMID: 36075246 BACKGROUND

• 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.

  PMID: 38545781 BACKGROUND

• 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.

  PMID: 37855448 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Hypercholesterolemia; Homozygous Familial Hypercholesterolemia

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: December 9, 2015
• Study Start: September 10, 2016
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: May 29, 2024
• Results First Posted: January 14, 2022

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

AU (3); HU (1); NL (1); ZA (2); CH (2); TU (2); CO (2); BR (4); BE (3); PL (1); SL (1); CA (3); MY (1); PT (1); ES (3); NO (2); GB (1); GR (2); IT (5); RU (1); CZ (1); US (3)