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

Primary Purpose

Hypercholesterolemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Evolocumab
Low-density Lipoprotein Cholesterol (LDL-C) Apheresis
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring LDL-C Apheresis, Hypercholesterolemia, Elevated Cholesterol, High Cholesterol, PCSK9 mutations, Severe Familial Hypercholesterolemia, evolocumab, Repatha

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Evolocumab

Low Density Lipoprotein Cholesterol (LDL-C) Apheresis

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Percent Change From Baseline in Low-density Lipoprotein Cholesterol
Percent Change From Baseline in Non-high-density Lipoprotein-Cholesterol
Percent Change From Baseline in Total Cholesterol/High-density Lipoprotein Cholesterol Ratio

Full Information

First Posted
October 7, 2015
Last Updated
November 4, 2022
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT02585895
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
December 21, 2015 (Actual)
Primary Completion Date
September 1, 2016 (Actual)
Study Completion Date
January 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
Keywords
LDL-C Apheresis, Hypercholesterolemia, Elevated Cholesterol, High Cholesterol, PCSK9 mutations, Severe Familial Hypercholesterolemia, evolocumab, Repatha

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Evolocumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Low Density Lipoprotein Cholesterol (LDL-C) Apheresis
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Evolocumab
Other Intervention Name(s)
Repatha, AMG 145
Intervention Description
Administered by subcutaneous injection once every 2 weeks
Intervention Type
Procedure
Intervention Name(s)
Low-density Lipoprotein Cholesterol (LDL-C) Apheresis
Intervention Description
Participants received apheresis for LDL-C according the their physician's prescription and local custom.
Primary Outcome Measure Information:
Title
Percentage of Participants With Apheresis Avoidance at the End of Randomized Therapy
Description
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.
Time Frame
Week 5 and week 6
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Low-density Lipoprotein Cholesterol
Time Frame
Baseline and week 4
Title
Percent Change From Baseline in Non-high-density Lipoprotein-Cholesterol
Time Frame
Baseline and Week 4
Title
Percent Change From Baseline in Total Cholesterol/High-density Lipoprotein Cholesterol Ratio
Time Frame
Baseline and Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33434
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Research Site
City
Grandville
State/Province
Michigan
ZIP/Postal Code
49418
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Research Site
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Research Site
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Research Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Research Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Research Site
City
Düsseldorf
ZIP/Postal Code
40210
Country
Germany
Facility Name
Research Site
City
Flensburg
ZIP/Postal Code
24939
Country
Germany
Facility Name
Research Site
City
Pisa
ZIP/Postal Code
56124
Country
Italy
Facility Name
Research Site
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Research Site
City
Sevilla
State/Province
Andalucía
ZIP/Postal Code
41013
Country
Spain
Facility Name
Research Site
City
Harefield
ZIP/Postal Code
UB9 6JH
Country
United Kingdom
Facility Name
Research Site
City
Penarth
ZIP/Postal Code
CF64 2XX
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.amgen.com/datasharing
Citations:
PubMed Identifier
31759938
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

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