Evolocumab Compared to LDL-C Apheresis in Patients Receiving LDL-C Apheresis Prior to Study Enrollment

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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Biological: Evolocumab; Procedure: Low-density Lipoprotein Cholesterol (LDL-C) Apheresis

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Research Site
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Research Site
• France
  • Bron, France, 69677
    • Research Site
  • Nantes Cedex 1, France, 44093
    • Research Site
• Germany
  • Berlin, Germany, 13353
    • Research Site
  • Dresden, Germany, 01307
    • Research Site
  • Düsseldorf, Germany, 40210
    • Research Site
  • Flensburg, Germany, 24939
    • Research Site
• Italy
  • Pisa, Italy, 56124
    • Research Site
  • Roma, Italy, 00161
    • Research Site
• Spain
  • Andalucía
    • Sevilla, Andalucía, Spain, 41013
      • Research Site
• United Kingdom
  • Harefield, United Kingdom, UB9 6JH
    • Research Site
  • Penarth, United Kingdom, CF64 2XX
    • Research Site
• United States
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
  • Michigan
    • Grandville, Michigan, United States, 49418
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Evolocumab; Participants received 140 mg evolocumab every 2 weeks (Q2W) administered by subcutaneous injection for 6 weeks during the primary period of the study. Starting at week 6 (beginning of the post-primary period), participants received 140 mg evolocumab Q2W up to week 24.	Biological: Evolocumab; Administered by subcutaneous injection once every 2 weeks; Other Names: Repatha; AMG 145
Active Comparator: Low Density Lipoprotein Cholesterol (LDL-C) Apheresis; Participants continued apheresis at the same schedule, every week (QW) or every two weeks (Q2W), as prior to study entry, for the first 6 weeks. Starting at week 6 (beginning of the post-primary period), participants received 140 mg evolocumab Q2W up to week 24.	Biological: Evolocumab; Administered by subcutaneous injection once every 2 weeks; Other Names: Repatha; AMG 145; Procedure: Low-density Lipoprotein Cholesterol (LDL-C) Apheresis; Participants received apheresis for LDL-C according the their physician's prescription and local custom.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Apheresis Avoidance at the End of Randomized Therapy	Avoidance of apheresis at end of randomized therapy was defined as no apheresis at week 5 and week 6. Aperesis at weeks 5 or 6 was based on LDL-C level at week 4: participants with LDL-C ≥ 100 mg/dL at week 4 received apheresis at week 5 (participants who received apheresis QW before study entry) or week 6 (participants who received apheresis Q2W prior to study entry). If LDL-C was < 100 mg/dL at week 4, no apheresis was performed at week 5 or week 6, irrespective of assigned treatment group. Participants who ended the study prior to week 6 were considered as not achieving apheresis avoidance.	Week 5 and week 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Low-density Lipoprotein Cholesterol	Baseline and week 4
Percent Change From Baseline in Non-high-density Lipoprotein-Cholesterol	Baseline and Week 4
Percent Change From Baseline in Total Cholesterol/High-density Lipoprotein Cholesterol Ratio	Baseline and Week 4

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): January 20, 2017

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: October 22, 2015
• First Posted (Estimate): October 26, 2015

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Elevated Cholesterol; Hypercholesterolemia; High Cholesterol; Repatha; evolocumab; PCSK9 mutations; LDL-C Apheresis; Severe Familial Hypercholesterolemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: 20140316; 2015-001343-37 (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 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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 URL below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No