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Trial record 1 of 1 for:    NCT02624869
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Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia) (HAUSER-OLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02624869
Recruitment Status : Completed
First Posted : December 9, 2015
Results First Posted : January 14, 2022
Last Update Posted : January 14, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Familial Hypercholesterolemia Biological: Evolocumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 163 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 10, 2016
Actual Primary Completion Date : June 1, 2021
Actual Study Completion Date : June 1, 2021


Arm Intervention/treatment
Experimental: Evolocumab
Participants receive 420 mg evolocumab administered by subcutaneous injection every 4 weeks (QM) for up to 80 weeks.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha®
  • AMG 145




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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. ]

    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.



Secondary Outcome Measures :
  1. Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HeFH Participants [ Time Frame: Baseline and week 80 ]
    For HeFH participants baseline was defined as the baseline value of the parent study 20120123.

  2. Percent Change From Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HoFH Participants [ Time Frame: Baseline and week 80 ]
    For HoFH participants baseline was defined as the baseline value in this study (20120124).

  3. Percent Change From Baseline to Week 80 in Non-HDL-C in HeFH Participants [ Time Frame: Baseline and week 80 ]
    For HeFH participants baseline was defined as the baseline value of the parent study 20120123.

  4. Percent Change From Baseline to Week 80 in Non-HDL-C in HoFH Participants [ Time Frame: Baseline and week 80 ]
    For HoFH participants baseline was defined as the baseline value in this study (20120124).

  5. Percent Change From Baseline to Week 80 in Apolipoprotein B in HeFH Participants [ Time Frame: Baseline and week 80 ]
    For HeFH participants baseline was defined as the baseline value in the parent study 20120123.

  6. Percent Change From Baseline to Week 80 in Apolipoprotein B in HoFH Participants [ Time Frame: Baseline and week 80 ]
    For HoFH participants baseline was defined as the baseline value in this study (20120124).

  7. Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HeFH Participants [ Time Frame: Baseline and week 80 ]
    For HeFH participants baseline was defined as the baseline value in the parent study 20120123.

  8. Percent Change From Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HoFH Participants [ Time Frame: Baseline and week 80 ]
    For HoFH participants baseline was defined as the baseline value in this study (20120124).

  9. Percent Change From Baseline to Week 80 in Apolipoprotein B / Apolipoprotein A1 Ratio in HeFH Participants [ Time Frame: Baseline and week 80 ]
    For HeFH participants baseline was defined as the baseline value in the parent study 20120123.

  10. Percent Change From Baseline to Week 80 in Apolipoprotein B/Apolipoprotein A1 Ratio in HoFH Participants [ Time Frame: Baseline and week 80 ]
    For HoFH participants baseline was defined as the baseline value in this study (20120124).

  11. Change From Baseline to Week 80 in LDL-C in HeFH Participants [ Time Frame: Baseline and week 80 ]
    For HeFH participants baseline was defined as the baseline value of the parent study 20120123.

  12. Change From Baseline to Week 80 in LDL-C in HoFH Participants [ Time Frame: Baseline and week 80 ]
    For HoFH participants baseline was defined as the baseline value in this study (20120124).

  13. Change From Baseline to Week 80 in Estradiol Levels [ Time Frame: Baseline and week 80 ]
    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).

  14. Change From Baseline to Week 80 in Testosterone Levels [ Time Frame: Baseline and week 80 ]
    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).

  15. Change From Baseline to Week 80 in Follicle Stimulating Hormone (FSH) Levels [ Time Frame: Baseline and week 80 ]
    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).

  16. Change From Baseline to Week 80 in Luteinizing Hormone (LH) Levels [ Time Frame: Baseline and week 80 ]
    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).

  17. Change From Baseline to Week 80 in Adenocorticotropic Hormone (ACTH) Levels [ Time Frame: Baseline and week 80 ]
    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).

  18. Change From Baseline to Week 80 in Dehydroepiandrosterone Sulfate (DHEA-S) Levels [ Time Frame: Baseline and week 80 ]
    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).

  19. Change From Baseline to Week 80 in Cortisol Levels [ Time Frame: Baseline and week 80 ]
    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).

  20. Number of Participants With Liver Function Test Abnormalities at Week 80 [ Time Frame: Week 80 ]
    Liver function tests included alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels and total bilirubin levels.

  21. Number of Participants With Abnormalities in Levels of Creatine Kinase (CK) at Week 80 [ Time Frame: 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.

  22. Change From Baseline to Week 80 in Carotid Intima-media Thickness (cIMT) [ Time Frame: Baseline and week 80 ]

    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.


  23. Change From Baseline in Height at Weeks 24, 48, and 80 [ Time Frame: Baseline and weeks 24, 48, and 80 ]
  24. Change From Baseline in Weight at Weeks 24, 48, and 80 [ Time Frame: Baseline and weeks 24, 48, and 80 ]
  25. Number of Participants With Change in Tanner Staging From Baseline to Week 80 [ Time Frame: Baseline and 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02624869


Locations
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United States, New York
Research Site
Bronx, New York, United States, 10467
United States, Ohio
Research Site
Cincinnati, Ohio, United States, 45227
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37212
Australia, New South Wales
Research Site
Camperdown, New South Wales, Australia, 2050
Austria
Research Site
Feldkirch, Austria, 6800
Research Site
Salzburg, Austria, 5020
Research Site
Wien, Austria, 1090
Belgium
Research Site
Gent, Belgium, 9000
Research Site
La Louvière, Belgium, 7100
Research Site
Leuven, Belgium, 3000
Brazil
Research Site
Fortaleza, Ceará, Brazil, 60430-270
Research Site
Brasília, Distrito Federal, Brazil, 71625-175
Research Site
São Paulo, Brazil, 04040-000
Research Site
São Paulo, Brazil, 05403-000
Canada, Quebec
Research Site
Chicoutimi, Quebec, Canada, G7H 5H6
Research Site
Chicoutimi, Quebec, Canada, G7H 7K9
Canada
Research Site
Quebec, Canada, G1V 4W2
Colombia
Research Site
Barranquilla, Atlántico, Colombia, 080020
Research Site
Bucaramanga, Santander, Colombia, 81004
Czechia
Research Site
Svitavy, Czechia, 568 25
Greece
Research Site
Athens, Greece, 17674
Research Site
Thessaloniki, Greece, 54642
Hungary
Research Site
Budapest, Hungary, 1094
Italy
Research Site
Palermo, Italy, 90127
Research Site
Pisa, Italy, 56124
Research Site
Roma, Italy, 00161
Research Site
Roma, Italy, 00165
Research Site
Torino, Italy, 10126
Malaysia
Research Site
Kota Bharu, Kelantan, Malaysia, 16150
Netherlands
Research Site
Amsterdam, Netherlands, 1066 EC
Norway
Research Site
Bergen, Norway, 5021
Research Site
Oslo, Norway, 0586
Poland
Research Site
Gdansk, Poland, 80-952
Portugal
Research Site
Guimaraes, Portugal, 4835-044
Russian Federation
Research Site
Saint Petersburg, Russian Federation, 191025
Slovenia
Research Site
Ljubljana, Slovenia, 1000
South Africa
Research Site
Parktown, Gauteng, South Africa, 2193
Research Site
Parow, Western Cape, South Africa, 7505
Spain
Research Site
Cordoba, Andalucía, Spain, 14004
Research Site
A Coruña, Galicia, Spain, 15001
Research Site
Lugo, Galicia, Spain, 27003
Switzerland
Research Site
Geneva 14, Switzerland, 1211
Research Site
Reinach, Switzerland, 4153
Turkey
Research Site
Ankara, Turkey, 06500
Research Site
Izmir, Turkey, 35100
United Kingdom
Research Site
Birmingham, United Kingdom, B4 6NH
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] May 27, 2020
Statistical Analysis Plan  [PDF] May 29, 2020

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02624869    
Other Study ID Numbers: 20120124
2015-002276-25 ( EudraCT Number )
First Posted: December 9, 2015    Key Record Dates
Results First Posted: January 14, 2022
Last Update Posted: January 14, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://www.amgen.com/datasharing
Keywords provided by Amgen:
Hypercholesterolemia
Elevated Cholesterol
High Cholesterol
PCSK9 mutations
Severe Familial Hypercholesterolemia
evolocumab
Repatha
Heterozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia
Pediatric
Paediatric
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Evolocumab
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents