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

Heterozygous Familial Hypercholesterolemia Clinical Trial

— HAUSER-RCT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02392559
• Other study ID #: 20120123
• Secondary ID: 2014-002277-11
• Status: Completed
• Phase: Phase 3
• Start date: March 24, 2016
• Est. completion date: November 25, 2019

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: November 25, 2019
• Est. primary completion date: November 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Heterozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• Evolocumab
Dose of subcutaneous evolocumab every 4 weeks
• Placebo
Dose of subcutaneous placebo treatment every 4 weeks

Locations

Country	Name	City	State
Australia	Research Site	Camperdown	New South Wales
Austria	Research Site	Feldkirch
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Bruxelles
Belgium	Research Site	La Louvière
Belgium	Research Site	Leuven
Brazil	Research Site	Brasília	Distrito Federal
Brazil	Research Site	Fortaleza	Ceará
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Vitória	Espírito Santo
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Quebec
Colombia	Research Site	Barranquilla	Atlántico
Colombia	Research Site	Floridablanca	Santander
Czechia	Research Site	Ostrava-Poruba
Czechia	Research Site	Praha 5
Czechia	Research Site	Svitavy
Finland	Research Site	Helsinki
Finland	Research Site	Kuopio
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Italy	Research Site	Palermo
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Torino
Malaysia	Research Site	Kota Bharu	Kelantan
Netherlands	Research Site	Amsterdam
New Zealand	Research Site	Christchurch
Norway	Research Site	Bergen
Norway	Research Site	Oslo
Poland	Research Site	Gdansk
Portugal	Research Site	Guimaraes
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Slovenia	Research Site	Ljubljana
South Africa	Research Site	Parow	Western Cape
South Africa	Research Site	Pretoria	Gauteng
Spain	Research Site	A Coruña	Galicia
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Cordoba	Andalucía
Spain	Research Site	Lugo	Galicia
Spain	Research Site	Sevilla	Andalucía
Switzerland	Research Site	Geneva 14
Switzerland	Research Site	Reinach
Taiwan	Research Site	Taipei
Turkey	Research Site	Ankara
Turkey	Research Site	Izmir
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	London
United States	Research Site	Asheville	North Carolina
United States	Research Site	Bronx	New York
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Farmington	Connecticut
United States	Research Site	Iowa City	Iowa
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Nashville	Tennessee
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Towson	Maryland
United States	Research Site	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Colombia,  Czechia,  Finland,  Greece,  Hungary,  Italy,  Malaysia,  Netherlands,  New Zealand,  Norway,  Poland,  Portugal,  Russian Federation,  Slovenia,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (3)

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. — View Citation

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 Jul 21. pii: S1933-2874(22)00210-0. doi: 10.1016/j.jacl.2022.07.005. [Epub ahead of print] — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mean Percent Change From Baseline to Mean of Weeks 22 and 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 IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.	Baseline, Week 22, Week 24
Secondary	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 IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.	Baseline, Week 24
Secondary	Percent Change From Baseline to Week 24 in Non-HDL-C	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
Secondary	Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)	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
Secondary	Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio	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
Secondary	Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio	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
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs	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.
Secondary	Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade = 3	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
Secondary	Change From Baseline Over Time in Systolic Blood Pressure		Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Secondary	Change From Baseline Over Time in Diastolic Blood Pressure		Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Secondary	Change From Baseline Over Time in Heart Rate		Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Secondary	Number of Participants Testing Positive for Anti-Evolocumab Antibodies		up to Week 24
Secondary	Serum Evolocumab Concentrations Over Time		Week 12, Week 22, Week 24

External Links

•   AmgenTrials clinical trials website