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

NCT02392559 | Completed Phase 3 Results DMC

• 2 other identifiers: 201201232014-002277-11
• Study Type: interventional
• Target: 158
• Locations: 25 countries
• Sites: 65

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.

Conditions

Heterozygous Familial Hypercholesterolemia

Keywords

Hypercholesterolemia; Elevated Cholesterol; High Cholesterol; Heterozygous Familial Hypercholesterolemia; PCSK9 mutations; Paediatric; pediatric; Childhood Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to Week 24 in LDL-C

  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.

  Baseline, Week 24

Secondary Outcomes (13)

• Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C

  Baseline, Week 22, Week 24

• Change From Baseline to Week 24 in LDL-C

  Baseline, Week 24

• Percent Change From Baseline to Week 24 in Non-HDL-C

  Baseline, Week 24

• Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)

  Baseline, Week 24

• Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio

  Baseline, Week 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching subcutaneous injection every 4 weeks (QM)

Drug: Placebo

EvoMab 420 mg QM

EXPERIMENTAL

Evolocumab subcutaneous injection QM

Drug: Evolocumab

Interventions

Evolocumab DRUG

Dose of subcutaneous evolocumab every 4 weeks

Also known as: AMG 145; EvoMab

EvoMab 420 mg QM

Placebo DRUG

Dose of subcutaneous placebo treatment every 4 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (66)

Research Site

Farmington, Connecticut, 06032, United States

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Wilmington, Delaware, 19803, United States

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Iowa City, Iowa, 52242, United States

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Towson, Maryland, 21204, United States

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Minneapolis, Minnesota, 55454, United States

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The Bronx, New York, 10467, United States

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Asheville, North Carolina, 28803, United States

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Cincinnati, Ohio, 45227, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Nashville, Tennessee, 37212, United States

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Salt Lake City, Utah, 84113, United States

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Morgantown, West Virginia, 26506, 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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Brussels, 1200, 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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Vitória, Espírito Santo, 29055-450, 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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Floridablanca, Santander Department, Colombia

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Ostrava-Poruba, 708 52, Czechia

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Prague, 150 06, Czechia

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Svitavy, 568 25, Czechia

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Helsinki, 00029, Finland

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Kuopio, 70029, Finland

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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, 1105 AZ, Netherlands

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Christchurch, 8011, New Zealand

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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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Moscow, 125412, Russia

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Saint Petersburg, 191025, Russia

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Ljubljana, 1000, Slovenia

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Pretoria, Gauteng, 0087, South Africa

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Parow, Western Cape, 7505, South Africa

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Córdoba, Andalusia, 14004, Spain

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Seville, Andalusia, 41013, Spain

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Barcelona, Catalonia, 08036, 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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Taipei, 11217, Taiwan

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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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London, WC1N 3JH, United Kingdom

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Related Publications (4)

• 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.

  PMID: 32865373 BACKGROUND

• 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.

  PMID: 30318065 BACKGROUND

• 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.

  PMID: 36210291 BACKGROUND

• 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.

  PMID: 33078867 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

evolocumab

Condition Hierarchy (Ancestors)

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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2015
• First Posted: March 19, 2015
• Study Start: March 24, 2016
• Primary Completion: November 25, 2019
• Study Completion: November 25, 2019
• Last Updated: November 8, 2022
• Results First Posted: July 15, 2020

Record last verified: 2022-11

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

BE (3); NL (1); TU (2); AU (3); US (12); CZ (3); MY (1); SL (1); FI (2); HU (1); RU (2); NO (2); IT (5); NZ (1); BR (5); CO (2); PT (1); PL (1); CA (3); ZA (2); CH (2); TW (1); GB (2); ES (5); GR (2)