Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia

NCT ID: NCT02833844

Last Updated: 2022-07-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

467 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-22

Study Completion Date

2020-01-27

Brief Summary

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The study is divided into 2 parts. The first part of the study will be double-blinded and will last for 24 weeks. During this time, participants will be randomized in a ratio of 2:1 to receive either evolocumab once monthly (QM) or placebo QM. The second part of the study is a 24-week open label extension period. During this time all participants will receive evolocumab QM.

The clinical hypothesis is that subcutaneous evolocumab QM will be well tolerated and will result in greater reduction of low density lipoprotein cholesterol (LDL-C), defined as percent change from baseline at Week 24, compared with placebo QM in human immunodeficiency virus (HIV)-positive participants with hyperlipidemia or mixed dyslipidemia.

Detailed Description

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Conditions

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Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Double-Blind Placebo SC QM/Open-Label Evolocumab 420 mg SC QM

Double-blind placebo subcutaneous (SC) injection every 4 weeks (QM) for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks.

Group Type EXPERIMENTAL

Evolocumab

Intervention Type DRUG

Dose of subcutaneous evolocumab QM

Placebo

Intervention Type DRUG

Dose of matching placebo QM

Double-Blind Evolocumab 420 mg SC QM/Open-Label Evolocumab 420 mg SC QM

Double-blind evolocumab SC injection QM for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks.

Group Type PLACEBO_COMPARATOR

Evolocumab

Intervention Type DRUG

Dose of subcutaneous evolocumab QM

Interventions

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Evolocumab

Dose of subcutaneous evolocumab QM

Intervention Type DRUG

Placebo

Dose of matching placebo QM

Intervention Type DRUG

Other Intervention Names

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EvoMab Repatha AMG 145

Eligibility Criteria

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Inclusion Criteria

* Male or female ≥ 18 years of age
* Known HIV infection with stable HIV therapy for ≥ 6 months
* Cluster of differentiation 4 (CD4) ≥ 250 cells/mm\^3 for ≥ 6 months
* HIV viral load ≤ 50 copies/mL at screening and ≤ 200 copies/mL for ≥ 6 months
* Subject on stable lipid-lowering therapy for ≥ 4 weeks prior to randomization and not expected to change during the duration of study
* For subjects with known clinical atherosclerotic cardiovascular disease (ASCVD), fasting LDL-C of ≥ 70 mg/dL or non-high density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL. For subjects without known clinical ASCVD: fasting LDL-C of ≥ 100 mg/dL or non-HDL-C of ≥ 130 mg/dL
* Fasting triglycerides ≤ 600 mg/dL (6.8 mmol/L)

Exclusion Criteria

* Taking a combination of background lipid-lowering therapy and HIV therapy known to have significant drug-drug interaction
* New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction (LVEF) \< 30%
* Known opportunistic infection/acquired immunodeficiency syndrome (AIDS) defining illness within 1 year prior to randomization
* Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months
* Type 1 diabetes, new-onset or poorly controlled type 2 diabetes
* Uncontrolled hypertension
* Taken a cholesteryl ester transfer protein inhibitor in the last 12 months
* Moderate to severe renal dysfunction
* Persistent active liver disease or hepatic dysfunction (Stable chronic hepatitis C of at least 1 year duration prior to randomization is allowed)
* Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or stage 1 prostate carcinoma) within the last 5 years prior to randomization
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Los Angeles, California, United States

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Hartford, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Washington D.C., District of Columbia, United States

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Washington D.C., District of Columbia, United States

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Miami, Florida, United States

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Tampa, Florida, United States

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Vero Beach, Florida, United States

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Augusta, Georgia, United States

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Berkley, Michigan, United States

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Detroit, Michigan, United States

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Southfield, Michigan, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Camden, New Jersey, United States

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Albany, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Cincinnati, Ohio, United States

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Falls Church, Virginia, United States

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Darlinghurst, New South Wales, Australia

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East Sydney, New South Wales, Australia

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Sydney, New South Wales, Australia

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Fortitude Valley, Queensland, Australia

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Melbourne, Victoria, Australia

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Prahran, Victoria, Australia

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Antwerp, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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São Paulo, São Paulo, Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Bordeaux, , France

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Lyon, , France

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Thessaloniki, , Greece

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Bologna, , Italy

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Genova, , Italy

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Milan, , Italy

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Modena, , Italy

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Pisa, , Italy

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Roma, , Italy

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Warsaw, , Poland

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Almada, , Portugal

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Aveiro, , Portugal

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Coimbra, , Portugal

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Porto, , Portugal

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Brasov, , Romania

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Bucharest, , Romania

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Constanța, , Romania

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Timișoara, , Romania

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Pretoria, Gauteng, South Africa

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Westdene, Gauteng, South Africa

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Bloemfontein, , South Africa

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Madrid, , Spain

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Madrid, , Spain

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Geneva, , Switzerland

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Lausanne, , Switzerland

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Lugano, , Switzerland

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Zurich, , Switzerland

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Countries

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United States Australia Belgium Brazil Canada France Greece Italy Poland Portugal Romania South Africa Spain Switzerland United Kingdom

References

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Boccara F, Kumar PN, Caramelli B, Calmy A, Lopez JAG, Bray S, Cyrille M, Rosenson RS; BEIJERINCK Investigators. Evolocumab in HIV-Infected Patients With Dyslipidemia: Primary Results of the Randomized, Double-Blind BEIJERINCK Study. J Am Coll Cardiol. 2020 May 26;75(20):2570-2584. doi: 10.1016/j.jacc.2020.03.025. Epub 2020 Mar 28.

Reference Type BACKGROUND
PMID: 32234462 (View on PubMed)

Boccara F, Kumar P, Caramelli B, Calmy A, Lopez JAG, Bray S, Cyrille M, Rosenson RS. Evolocumab treatment in patients with HIV and hypercholesterolemia/mixed dyslipidemia: BEIJERINCK study design and baseline characteristics. Am Heart J. 2020 Feb;220:203-212. doi: 10.1016/j.ahj.2019.11.004. Epub 2019 Nov 12.

Reference Type BACKGROUND
PMID: 31841795 (View on PubMed)

Boccara F, Caramelli B, Calmy A, Kumar P, Lopez JAG, Bray S, Cyrille M, Rosenson RS; investigators of the BEIJERINCK study. Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period. AIDS. 2022 Apr 1;36(5):675-682. doi: 10.1097/QAD.0000000000003175.

Reference Type BACKGROUND
PMID: 35025817 (View on PubMed)

Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.

Reference Type DERIVED
PMID: 33078867 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2015-004735-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20130286

Identifier Type: -

Identifier Source: org_study_id

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