Clinical trial NCT02585895: Evolocumab Compared to LDL-C Apheresis in Patients Receiving LDL-C Apheresis Prior to Study Enrollment
Official title: A Randomized, Actively Controlled, Open-label, Multicenter Study of Efficacy and Safety of Evolocumab Compared With Low Density Lipoprotein Cholesterol (LDL-C) Apheresis, Followed by Single-Arm Evolocumab Administration in Subjects Receiving LDL-C Apheresis Prior to Study Enrollment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: LDL-C Apheresis
Hypercholesterolemia
Elevated Cholesterol
High Cholesterol
PCSK9 mutations
Severe Familial Hypercholesterolemia
evolocumab
Repatha
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-10-26
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of subcutaneous (SC) evolocumab, compared to regularly scheduled low-density lipoprotein cholesterol (LDL-C) apheresis, on reducing the need for future apheresis.


Eligibility criteria: Inclusion Criteria:

* Male or female, ≥ 18 years of age
* Subject has been receiving regular apheresis for LDL-C lowering for at least 3 months immediately prior to lipid screening and has a treatment goal of LDL-C \< 100 mg/dL (2.6 mmol/L), and has been receiving LDL-C apheresis during the last ≥ 4 weeks prior to lipid screening at regular QW or Q2W schedule and with no changes in apheresis type
* Subject is receiving lipid-lowering pharmacological background therapy which includes a high-intensity statin dose (moderate-intensity statin dose with attestation that a higher dose is not appropriate for the subject) unless the subject has a history of statin intolerance
* Lipid-lowering therapy status (ie, any therapy for lowering lipids, including apheresis type and frequency) must be unchanged for ≥ 4 weeks prior to LDL-C screening
* Pre-apheresis LDL-C is ≥ 100 mg/dL (≥ 2.6 mmol/L) and ≤ 190 mg/dL (≤ 4.9 mmol/L) at screening
* Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) at screening.

Exclusion criteria:

* Known homozygous familial hypercholesterolemia
* Missing any apheresis session is medically contraindicated or inappropriate
* Stopping apheresis would be inappropriate in the opinion of the investigator even if LDL-C is controlled to \< 100 mg/dL with other therapies
* Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization.
* Uncontrolled hypertension

Primary outcomes:
measure: Percentage of Participants With Apheresis Avoidance at the End of Randomized Therapy
timeFrame: Week 5 and week 6
Secondary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol
timeFrame: Baseline and week 4
measure: Percent Change From Baseline in Non-high-density Lipoprotein-Cholesterol
timeFrame: Baseline and Week 4
measure: Percent Change From Baseline in Total Cholesterol/High-density Lipoprotein Cholesterol Ratio
timeFrame: Baseline and Week 4
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Grandville
country: United States
facility: Research Site
state: Michigan
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Heidelberg
country: Australia
facility: Research Site
state: Victoria
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Bron
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Düsseldorf
country: Germany
facility: Research Site
city: Flensburg
country: Germany
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
state: Andalucía
city: Harefield
country: United Kingdom
facility: Research Site
city: Penarth
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Baum SJ, Sampietro T, Datta D, Moriarty PM, Knusel B, Schneider J, Somaratne R, Kurtz C, Hohenstein B. Effect of evolocumab on lipoprotein apheresis requirement and lipid levels: Results of the randomized, controlled, open-label DE LAVAL study. J Clin Lipidol. 2019 Nov-Dec;13(6):901-909.e3. doi: 10.1016/j.jacl.2019.10.003. Epub 2019 Oct 11.