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

NCT02833844 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 201302862015-004735-12
• Study Type: interventional
• Target: 467
• Locations: 15 countries
• Sites: 78

Brief Summary

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.

Conditions

Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection

Keywords

Hyperlipidemia; Dyslipidemia; Proprotein convertase subtilisin/kexin type 9 (PCSK9); Inhibition; HIV infection; Cluster of differentiation; Viral load

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Change From Baseline in LDL-C at Week 24

  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

  Baseline, Week 24

• Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24

  Baseline, Week 24

Study Arms (2)

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

EXPERIMENTAL

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; Drug: Placebo

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

PLACEBO COMPARATOR

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

Drug: Evolocumab

Interventions

Evolocumab DRUG

Dose of subcutaneous evolocumab QM

Also known as: EvoMab, Repatha, AMG 145

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

Placebo DRUG

Dose of matching placebo QM

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

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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (78)

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Los Angeles, California, 90035, United States

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Hartford, Connecticut, 06102, United States

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Washington D.C., District of Columbia, 20005, United States

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Washington D.C., District of Columbia, 20007, United States

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Washington D.C., District of Columbia, 20037, United States

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Miami, Florida, 33136, United States

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Tampa, Florida, 33602, United States

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Vero Beach, Florida, 32960, United States

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Augusta, Georgia, 30912, United States

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Berkley, Michigan, 48072, United States

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Detroit, Michigan, 48202, United States

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Southfield, Michigan, 48075, United States

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Minneapolis, Minnesota, 55415, United States

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St Louis, Missouri, 63110, United States

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Camden, New Jersey, 08103, United States

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Albany, New York, 12208, United States

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New York, New York, 10029, United States

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The Bronx, New York, 10467, United States

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Cincinnati, Ohio, 45267, United States

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Falls Church, Virginia, 22042, United States

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Darlinghurst, New South Wales, 2010, Australia

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East Sydney, New South Wales, 2010, Australia

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Sydney, New South Wales, 2010, Australia

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Fortitude Valley, Queensland, 4006, Australia

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Melbourne, Victoria, 3004, Australia

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Prahran, Victoria, 3181, Australia

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Antwerp, 2000, Belgium

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Brussels, 1000, Belgium

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Ghent, 9000, Belgium

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São Paulo, São Paulo, 04121-000, Brazil

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Rio de Janeiro, 21040-900, Brazil

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São Paulo, 05403-000, Brazil

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Calgary, Alberta, T2R 0X7, Canada

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Vancouver, British Columbia, V6Z 1Y6, Canada

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Hamilton, Ontario, L8S 1A4, Canada

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Montreal, Quebec, H4A 3T2, Canada

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Québec, Quebec, G1V 4G2, Canada

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Bordeaux, 33075, France

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Lyon, 69317, France

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Montpellier, 34295, France

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Nantes, 44093, France

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Paris, 75475, France

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Paris, 75571, France

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Paris, 75651, France

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Athens, 10676, Greece

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Athens, 11527, Greece

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Athens, 12462, Greece

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Athens, 16121, Greece

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Thessaloniki, 54636, Greece

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Bologna, 40138, Italy

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Genova, 16132, Italy

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Milan, 20157, Italy

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Modena, 41100, Italy

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Pisa, 56124, Italy

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Roma, 00149, Italy

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Warsaw, 01-201, Poland

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Almada, 2801-951, Portugal

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Aveiro, 3814-501, Portugal

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Coimbra, 3000-075, Portugal

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Porto, 4200-319, Portugal

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Brasov, 500174, Romania

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Bucharest, 021105, Romania

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Constanța, 900708, Romania

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Timișoara, 300310, Romania

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Pretoria, Gauteng, 0122, South Africa

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Westdene, Gauteng, 2092, South Africa

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Bloemfontein, 9301, South Africa

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Barcelona, Catalonia, 08035, Spain

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Barcelona, Catalonia, 08036, Spain

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Madrid, 28040, Spain

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Madrid, 28046, Spain

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Geneva, 1211, Switzerland

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Lausanne, 1011, Switzerland

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Lugano, 6900, Switzerland

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Zurich, 8091, Switzerland

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London, SE1 9RT, United Kingdom

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London, SW10 9NH, United Kingdom

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London, W2 1NY, United Kingdom

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Related Publications (4)

• 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.

  PMID: 32234462 BACKGROUND

• 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.

  PMID: 31841795 BACKGROUND

• 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.

  PMID: 35025817 BACKGROUND

• 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.

  PMID: 33078867 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Dyslipidemias; HIV Infections; Hyperlipidemias; Hypercholesterolemia, Autosomal Dominant, 3; Inhibition, Psychological

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Behavior

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2016
• First Posted: July 14, 2016
• Study Start: May 22, 2017
• Primary Completion: July 9, 2019
• Study Completion: January 27, 2020
• Last Updated: July 22, 2022
• Results First Posted: July 21, 2020

Record last verified: 2022-07

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 (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.
• 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.

Locations

US (20); PT (4); BE (3); AU (6); IT (6); RO (4); GR (5); BR (3); FR (7); PL (1); ES (4); CH (4); GB (3); CA (5); ZA (3)