- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02392559
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
158
Phase
- 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
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Research Site
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Feldkirch, Austria, 6800
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Salzburg, Austria, 5020
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Wien, Austria, 1090
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Bruxelles, Belgium, 1200
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La Louvière, Belgium, 7100
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Leuven, Belgium, 3000
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São Paulo, Brazil, 05403-000
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São Paulo, Brazil, 04040-000
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Ceará
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Fortaleza, Ceará, Brazil, 60430-270
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Distrito Federal
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Brasília, Distrito Federal, Brazil, 71625-175
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Espírito Santo
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Vitória, Espírito Santo, Brazil, 29055-450
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Quebec, Canada, G1V 4W2
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Quebec
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Chicoutimi, Quebec, Canada, G7H 5H6
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Chicoutimi, Quebec, Canada, G7H 7K9
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Atlántico
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Barranquilla, Atlántico, Colombia, 080020
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Santander
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Floridablanca, Santander, Colombia
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Ostrava-Poruba, Czechia, 708 52
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Praha 5, Czechia, 150 06
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Svitavy, Czechia, 568 25
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Helsinki, Finland, 00029
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Kuopio, Finland, 70029
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Athens, Greece, 17674
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Thessaloniki, Greece, 54642
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Budapest, Hungary, 1094
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Palermo, Italy, 90127
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Pisa, Italy, 56124
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Roma, Italy, 00161
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Roma, Italy, 00165
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Torino, Italy, 10126
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Kelantan
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Kota Bharu, Kelantan, Malaysia, 16150
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Amsterdam, Netherlands, 1105 AZ
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Christchurch, New Zealand, 8011
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Bergen, Norway, 5021
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Oslo, Norway, 0586
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Gdansk, Poland, 80-952
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Guimaraes, Portugal, 4835-044
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Moscow, Russian Federation, 125412
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Saint Petersburg, Russian Federation, 191025
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Ljubljana, Slovenia, 1000
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Gauteng
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Pretoria, Gauteng, South Africa, 0087
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Western Cape
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Parow, Western Cape, South Africa, 7505
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Andalucía
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Cordoba, Andalucía, Spain, 14004
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Sevilla, Andalucía, Spain, 41013
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Cataluña
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Barcelona, Cataluña, Spain, 08036
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Galicia
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A Coruña, Galicia, Spain, 15001
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Lugo, Galicia, Spain, 27003
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Geneva 14, Switzerland, 1211
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Reinach, Switzerland, 4153
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Taipei, Taiwan, 11217
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Ankara, Turkey, 06500
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Izmir, Turkey, 35100
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Birmingham, United Kingdom, B4 6NH
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London, United Kingdom, WC1N 3JH
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Connecticut
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Farmington, Connecticut, United States, 06032
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Delaware
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Wilmington, Delaware, United States, 19803
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Iowa
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Iowa City, Iowa, United States, 52242
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Maryland
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Towson, Maryland, United States, 21204
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Minnesota
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Minneapolis, Minnesota, United States, 55454
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New York
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Bronx, New York, United States, 10467
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North Carolina
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Asheville, North Carolina, United States, 28803
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Ohio
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Cincinnati, Ohio, United States, 45227
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15224
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Tennessee
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Nashville, Tennessee, United States, 37212
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Utah
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Salt Lake City, Utah, United States, 84113
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West Virginia
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Morgantown, West Virginia, United States, 26506
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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
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 |
Intervention / Treatment |
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Placebo Comparator: Placebo
Matching subcutaneous injection every 4 weeks (QM)
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Dose of subcutaneous placebo treatment every 4 weeks
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Experimental: EvoMab 420 mg QM
Evolocumab subcutaneous injection QM
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Dose of subcutaneous evolocumab every 4 weeks
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percent Change From Baseline to Week 24 in LDL-C
Time Frame: Baseline, Week 24
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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.
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Baseline, Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C
Time Frame: Baseline, Week 22, Week 24
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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.
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Baseline, Week 22, Week 24
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Change From Baseline to Week 24 in LDL-C
Time Frame: Baseline, Week 24
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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.
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Baseline, Week 24
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Percent Change From Baseline to Week 24 in Non-HDL-C
Time Frame: Baseline, Week 24
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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
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Baseline, Week 24
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Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)
Time Frame: Baseline, Week 24
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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.
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Baseline, Week 24
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Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio
Time Frame: Baseline, Week 24
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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.
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Baseline, Week 24
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Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio
Time Frame: Baseline, Week 24
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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.
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Baseline, Week 24
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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.
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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.
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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.
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Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3
Time Frame: Week 24
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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.
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Week 24
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Change From Baseline Over Time in Systolic Blood Pressure
Time Frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
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Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
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Change From Baseline Over Time in Diastolic Blood Pressure
Time Frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
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Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
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Change From Baseline Over Time in Heart Rate
Time Frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
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Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
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Number of Participants Testing Positive for Anti-Evolocumab Antibodies
Time Frame: up to Week 24
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up to Week 24
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Serum Evolocumab Concentrations Over Time
Time Frame: Week 12, Week 22, Week 24
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Week 12, Week 22, Week 24
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
- 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.
- 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.
- 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.
- 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.
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)
March 24, 2016
Primary Completion (Actual)
November 25, 2019
Study Completion (Actual)
November 25, 2019
Study Registration Dates
First Submitted
February 25, 2015
First Submitted That Met QC Criteria
March 13, 2015
First Posted (Estimate)
March 19, 2015
Study Record Updates
Last Update Posted (Actual)
November 8, 2022
Last Update Submitted That Met QC Criteria
November 4, 2022
Last Verified
November 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lipid Metabolism Disorders
- Hyperlipidemias
- Dyslipidemias
- Lipid Metabolism, Inborn Errors
- Hyperlipoproteinemias
- Hypercholesterolemia
- Hyperlipoproteinemia Type II
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Evolocumab
Other Study ID 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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