Clinical trial NCT01588496: Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities
Official title: 2-part, Phase 2/3 Study to Assess the Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia. Part A - Open-label, Single-arm, Multicenter Pilot Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia. Part B - Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: hypercholesterolemia
familial hypercholesterolemia
homozygous familial hypercholesterolemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-05-01
Enrollment: 58
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to determine the safety, tolerability, and efficacy of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia (HoFH).

Detailed description: Study Masking:

Part A: Open Label Part B: Double Blind

Eligibility criteria: Inclusion Criteria:

* Males and females ≥ 12 to ≤ 80 years of age
* Diagnosis of homozygous familial hypercholesterolemia
* Stable lipid-lowering therapies for at least 4 weeks
* LDL cholesterol ≥ 130 mg/dl (3.4 mmol/L)
* Triglyceride ≤ 400 mg/dL (4.5 mmol/L)
* Bodyweight of ≥ 40 kg at screening.

Exclusion Criteria:

* LDL or plasma apheresis within 8 weeks prior to randomization
* New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction \< 30%
* Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of randomization
* Planned cardiac surgery or revascularization
* Uncontrolled cardiac arrhythmia
* Uncontrolled hypertension

Primary outcomes:
measure: Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
timeFrame: Baseline and Week 12
measure: Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Part A: Change From Baseline in LDL-C at Week 12
timeFrame: Baseline and Week 12
measure: Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
timeFrame: Baseline and Week 12
measure: Part A: Percent Change From Baseline in Apolipoprotein B at Week 12
timeFrame: Baseline and Week 12
measure: Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
timeFrame: Baseline and Week 12
measure: Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
timeFrame: Baseline and Week 12
measure: Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12
timeFrame: Baseline and Week 12
measure: Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12
timeFrame: Baseline and Week 12
measure: Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12
timeFrame: Baseline and Weeks 6 and 12
measure: Part B: Percent Change From Baseline in Apolipoprotein B at Week 12
timeFrame: Baseline and Week 12
measure: Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12
timeFrame: Baseline and Weeks 6 and 12
measure: Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12
timeFrame: Baseline and Week 12
measure: Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12
timeFrame: Baseline and Weeks 6 and 12
Other outcomes:
Locations:
city: New York
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Bruxelles
country: Belgium
facility: Research Site
city: La Louvière
country: Belgium
facility: Research Site
city: London
country: Canada
facility: Research Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Uherske Hradiste
country: Czechia
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: New Territories
country: Hong Kong
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Beirut
country: Lebanon
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Observatory
country: South Africa
facility: Research Site
state: Western Cape
city: Cordoba
country: Spain
facility: Research Site
state: Andalucía
city: Lugo
country: Spain
facility: Research Site
state: Galicia
city: Madrid
country: Spain
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
citation: Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, Wasserman SM, Stein EA; TESLA Investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jan 24;385(9965):341-50. doi: 10.1016/S0140-6736(14)61374-X. Epub 2014 Oct 1.
citation: Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013 Nov 5;128(19):2113-20. doi: 10.1161/CIRCULATIONAHA.113.004678. Epub 2013 Sep 6.