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

NCT02585895 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 201403162015-001343-37
• Study Type: interventional
• Target: 39
• Locations: 8 countries
• Sites: 17

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.

Conditions

Hypercholesterolemia

Keywords

LDL-C Apheresis; Hypercholesterolemia; Elevated Cholesterol; High Cholesterol; PCSK9 mutations; Severe Familial Hypercholesterolemia; evolocumab; Repatha

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

Evolocumab

EXPERIMENTAL

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

Low Density Lipoprotein Cholesterol (LDL-C) Apheresis

ACTIVE COMPARATOR

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; Procedure: Low-density Lipoprotein Cholesterol (LDL-C) Apheresis

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection once every 2 weeks

Also known as: Repatha, AMG 145

Evolocumab; Low Density Lipoprotein Cholesterol (LDL-C) Apheresis

Low-density Lipoprotein Cholesterol (LDL-C) Apheresis PROCEDURE

Participants received apheresis for LDL-C according the their physician's prescription and local custom.

Low Density Lipoprotein Cholesterol (LDL-C) Apheresis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (17)

Research Site

Boca Raton, Florida, 33434, United States

Location

Research Site

Kansas City, Kansas, 66160, United States

Location

Research Site

Grandville, Michigan, 49418, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Heidelberg, Victoria, 3084, Australia

Location

Research Site

Hradec Králové, 500 05, Czechia

Location

Research Site

Bron, 69677, France

Location

Research Site

Nantes, 44093, France

Location

Research Site

Berlin, 13353, Germany

Location

Research Site

Dresden, 01307, Germany

Location

Research Site

Düsseldorf, 40210, Germany

Location

Research Site

Flensburg, 24939, Germany

Location

Research Site

Pisa, 56124, Italy

Location

Research Site

Roma, 00161, Italy

Location

Research Site

Seville, Andalusia, 41013, Spain

Location

Research Site

Harefield, UB9 6JH, United Kingdom

Location

Research Site

Penarth, CF64 2XX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31759938 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipoproteinemia Type II

Interventions

evolocumab; Cholesterol, LDL; Blood Component Removal

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Intervention Hierarchy (Ancestors)

Cholesterol; Sterols; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Lipoproteins, LDL; Lipoproteins; Lipids; Membrane Lipids; Proteins; Amino Acids, Peptides, and Proteins; Therapeutics

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 26, 2015
• Study Start: December 21, 2015
• Primary Completion: September 1, 2016
• Study Completion: January 20, 2017
• Last Updated: November 30, 2022
• Results First Posted: September 19, 2017

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

AU (1); CZ (1); FR (2); US (4); ES (1); DE (4); IT (2); GB (2)