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 (HAUSER-RCT)

November 4, 2022 updated by: Amgen

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

A study to assess safety and efficacy of evolocumab (AMG-145) in paediatric subjects aged 10-17 years diagnosed with heterozygous familial hypercholesterolemia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
158

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Research Site
  • Austria
      • Feldkirch, Austria, 6800
        • Research Site
      • Salzburg, Austria, 5020
        • Research Site
      • Wien, Austria, 1090
        • Research Site
  • Belgium
      • Bruxelles, Belgium, 1200
        • Research Site
      • La Louvière, Belgium, 7100
        • Research Site
      • Leuven, Belgium, 3000
        • Research Site
  • Brazil
      • São Paulo, Brazil, 05403-000
        • Research Site
      • São Paulo, Brazil, 04040-000
        • Research Site
    • Ceará
      • Fortaleza, Ceará, Brazil, 60430-270
        • Research Site
    • Distrito Federal
      • Brasília, Distrito Federal, Brazil, 71625-175
        • Research Site
    • Espírito Santo
      • Vitória, Espírito Santo, Brazil, 29055-450
        • Research Site
  • Canada
      • Quebec, Canada, G1V 4W2
        • Research Site
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 5H6
        • Research Site
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Research Site
  • Colombia
    • Atlántico
      • Barranquilla, Atlántico, Colombia, 080020
        • Research Site
    • Santander
      • Floridablanca, Santander, Colombia
        • Research Site
  • Czechia
      • Ostrava-Poruba, Czechia, 708 52
        • Research Site
      • Praha 5, Czechia, 150 06
        • Research Site
      • Svitavy, Czechia, 568 25
        • Research Site
  • Finland
      • Helsinki, Finland, 00029
        • Research Site
      • Kuopio, Finland, 70029
        • Research Site
  • Greece
      • Athens, Greece, 17674
        • Research Site
      • Thessaloniki, Greece, 54642
        • Research Site
  • Hungary
      • Budapest, Hungary, 1094
        • Research Site
  • Italy
      • Palermo, Italy, 90127
        • Research Site
      • Pisa, Italy, 56124
        • Research Site
      • Roma, Italy, 00161
        • Research Site
      • Roma, Italy, 00165
        • Research Site
      • Torino, Italy, 10126
        • Research Site
  • Malaysia
    • Kelantan
      • Kota Bharu, Kelantan, Malaysia, 16150
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Research Site
  • New Zealand
      • Christchurch, New Zealand, 8011
        • Research Site
  • Norway
      • Bergen, Norway, 5021
        • Research Site
      • Oslo, Norway, 0586
        • Research Site
  • Poland
      • Gdansk, Poland, 80-952
        • Research Site
  • Portugal
      • Guimaraes, Portugal, 4835-044
        • Research Site
  • Russian Federation
      • Moscow, Russian Federation, 125412
        • Research Site
      • Saint Petersburg, Russian Federation, 191025
        • Research Site
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Research Site
  • South Africa
    • Gauteng
      • Pretoria, Gauteng, South Africa, 0087
        • Research Site
    • Western Cape
      • Parow, Western Cape, South Africa, 7505
        • Research Site
  • Spain
    • Andalucía
      • Cordoba, Andalucía, Spain, 14004
        • Research Site
      • Sevilla, Andalucía, Spain, 41013
        • Research Site
    • Cataluña
      • Barcelona, Cataluña, Spain, 08036
        • Research Site
    • Galicia
      • A Coruña, Galicia, Spain, 15001
        • Research Site
      • Lugo, Galicia, Spain, 27003
        • Research Site
  • Switzerland
      • Geneva 14, Switzerland, 1211
        • Research Site
      • Reinach, Switzerland, 4153
        • Research Site
  • Taiwan
      • Taipei, Taiwan, 11217
        • Research Site
  • Turkey
      • Ankara, Turkey, 06500
        • Research Site
      • Izmir, Turkey, 35100
        • Research Site
  • United Kingdom
      • Birmingham, United Kingdom, B4 6NH
        • Research Site
      • London, United Kingdom, WC1N 3JH
        • Research Site
  • United States
    • Connecticut
      • Farmington, Connecticut, United States, 06032
        • Research Site
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Research Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Research Site
    • Maryland
      • Towson, Maryland, United States, 21204
        • Research Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • Research Site
    • New York
      • Bronx, New York, United States, 10467
        • Research Site
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Research Site
    • Ohio
      • Cincinnati, Ohio, United States, 45227
        • Research Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Research Site
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Research Site
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

10 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Matching subcutaneous injection every 4 weeks (QM)
Drug: Placebo
Dose of subcutaneous placebo treatment every 4 weeks
Experimental: EvoMab 420 mg QM
Evolocumab subcutaneous injection QM
Drug: Evolocumab
Dose of subcutaneous evolocumab every 4 weeks
Other Names:
  • AMG 145; EvoMab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline to Week 24 in LDL-C
Time Frame: Baseline, Week 24
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C
Time Frame: Baseline, Week 22, Week 24
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Baseline, Week 22, Week 24
Change From Baseline to Week 24 in LDL-C
Time Frame: Baseline, Week 24
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Baseline, Week 24
Percent Change From Baseline to Week 24 in Non-HDL-C
Time Frame: Baseline, Week 24
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates
Baseline, Week 24
Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)
Time Frame: Baseline, Week 24
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Baseline, Week 24
Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio
Time Frame: Baseline, Week 24
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Baseline, Week 24
Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio
Time Frame: Baseline, Week 24
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Baseline, Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs
Time Frame: 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.
An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. An SAE is defined as an adverse event that: is fatal; is a life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other medically important serious event. Events were graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading scale (1=mild; 2=moderate; 3=severe; 4=life-threatening; 5=death). Events were defined as treatment emergent if they occurred after the first dose of study drug and up to and including 30 days after the last dose or the end of study date, whichever is earlier.
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.
Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3
Time Frame: Week 24
Laboratory toxicity grading was based on NCI CTCAE grading. Grade 3 indicates severe toxicity and Grade 4 indicates life-threatening toxicity. Values representing a worsening from baseline are shown.
Week 24
Change From Baseline Over Time in Systolic Blood Pressure
Time Frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Change From Baseline Over Time in Diastolic Blood Pressure
Time Frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Change From Baseline Over Time in Heart Rate
Time Frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Number of Participants Testing Positive for Anti-Evolocumab Antibodies
Time Frame: up to Week 24
up to Week 24
Serum Evolocumab Concentrations Over Time
Time Frame: Week 12, Week 22, Week 24
Week 12, Week 22, Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 24, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 25, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 25, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 25, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 19, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 8, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20120123
  • 2014-002277-11 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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