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

A Double Blind, Randomized, Placebo Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy on LDL-C of Evolocumab (AMG 145) in Subjects With HIV and With Hyperlipidemia and/or Mixed Dyslipidemia

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.

Study Overview

• Status: Completed
• Conditions: Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection
• Intervention / Treatment: Drug: Evolocumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 467
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Research Site
    • East Sydney, New South Wales, Australia, 2010
      • Research Site
    • Sydney, New South Wales, Australia, 2010
      • Research Site
  • Queensland
    • Fortitude Valley, Queensland, Australia, 4006
      • Research Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Research Site
    • Prahran, Victoria, Australia, 3181
      • Research Site
• Belgium
  • Antwerp, Belgium, 2000
    • Research Site
  • Brussels, Belgium, 1000
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
• Brazil
  • Rio de Janeiro, Brazil, 21040-900
    • Research Site
  • São Paulo, Brazil, 05403-000
    • Research Site
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 04121-000
      • Research Site
• Canada
  • Quebec, Canada, G1V 4G2
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada, T2R 0X7
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1A4
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3T2
      • Research Site
• France
  • Bordeaux, France, 33075
    • Research Site
  • Lyon cedex 04, France, 69317
    • Research Site
  • Montpellier cedex 5, France, 34295
    • Research Site
  • Nantes Cedex 1, France, 44093
    • Research Site
  • Paris Cedex 10, France, 75475
    • Research Site
  • Paris Cedex 12, France, 75571
    • Research Site
  • Paris Cedex 13, France, 75651
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Research Site
  • Athens, Greece, 12462
    • Research Site
  • Athens, Greece, 10676
    • Research Site
  • Athens, Greece, 16121
    • Research Site
  • Thessaloniki, Greece, 54636
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Milano, Italy, 20157
    • Research Site
  • Modena, Italy, 41100
    • Research Site
  • Pisa, Italy, 56124
    • Research Site
  • Roma, Italy, 00149
    • Research Site
• Poland
  • Warszawa, Poland, 01-201
    • Research Site
• Portugal
  • Almada, Portugal, 2801-951
    • Research Site
  • Aveiro, Portugal, 3814-501
    • Research Site
  • Coimbra, Portugal, 3000-075
    • Research Site
  • Porto, Portugal, 4200-319
    • Research Site
• Romania
  • Brasov, Romania, 500174
    • Research Site
  • Bucharest, Romania, 021105
    • Research Site
  • Constanta, Romania, 900708
    • Research Site
  • Timisoara, Romania, 300310
    • Research Site
• South Africa
  • Bloemfontein, South Africa, 9301
    • Research Site
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0122
      • Research Site
    • Westdene, Gauteng, South Africa, 2092
      • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
• Switzerland
  • Geneva 14, Switzerland, 1211
    • Research Site
  • Lausanne, Switzerland, 1011
    • Research Site
  • Lugano, Switzerland, 6900
    • Research Site
  • Zuerich, Switzerland, 8091
    • Research Site
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Research Site
  • London, United Kingdom, W2 1NY
    • Research Site
  • London, United Kingdom, SW10 9NH
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90035
      • Research Site
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site
    • Washington, District of Columbia, United States, 20037
      • Research Site
    • Washington, District of Columbia, United States, 20005
      • Research Site
  • Florida
    • Miami, Florida, United States, 33136
      • Research Site
    • Tampa, Florida, United States, 33602
      • Research Site
    • Vero Beach, Florida, United States, 32960
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Research Site
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Research Site
    • Detroit, Michigan, United States, 48202
      • Research Site
    • Southfield, Michigan, United States, 48075
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Research Site
  • New York
    • Albany, New York, United States, 12208
      • Research Site
    • Bronx, New York, United States, 10467
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Research Site
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • 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
• 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

Other exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Evolocumab; Dose of subcutaneous evolocumab QM; Other Names: Repatha; AMG 145; EvoMab; Drug: Placebo; Dose of matching placebo QM
PLACEBO_COMPARATOR: 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.	Drug: Evolocumab; Dose of subcutaneous evolocumab QM; Other Names: Repatha; AMG 145; EvoMab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in LDL-C at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in LDL-C at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24
Percentage of Participants Acheiving LDL-C < 70 mg/dL (1.8 mmol/L) at Week 24		Week 24
Percentage of Participants With an LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 24		Baseline, Week 24
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24
Percent Change From Baseline in Total Cholesterol (TC) at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24
Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24
Percent Change From Baseline in Triglycerides at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24
Percent Change From Baseline in HDL-C at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Bseline, Week 24
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24	Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: J Am Coll Cardiol. 2020 Aug 11;76(6):762-765.
• 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.
• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 22, 2017
• Primary Completion (ACTUAL): July 9, 2019
• Study Completion (ACTUAL): January 27, 2020

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: July 12, 2016
• First Posted (ESTIMATE): July 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 15, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Dyslipidemia; Hyperlipidemia; HIV infection; Viral load; Inhibition; Proprotein convertase subtilisin/kexin type 9 (PCSK9); Cluster of differentiation
• Additional Relevant MeSH Terms: Metabolic Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Lipid Metabolism Disorders; HIV Infections; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: 20130286; 2015-004735-12 (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 (or other new use) 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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 link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; 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