Clinical trial NCT02833844: Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2016-07-14
Enrollment: 467
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in LDL-C at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in LDL-C at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Acheiving LDL-C < 70 mg/dL (1.8 mmol/L) at Week 24
timeFrame: Week 24
measure: Percentage of Participants With an LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Total Cholesterol (TC) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Triglycerides at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in HDL-C at Week 24
timeFrame: Bseline, Week 24
measure: Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Hartford
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Miami
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Vero Beach
country: United States
facility: Research Site
state: Florida
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Berkley
country: United States
facility: Research Site
state: Michigan
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Southfield
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Camden
country: United States
facility: Research Site
state: New Jersey
city: Albany
country: United States
facility: Research Site
state: New York
city: Bronx
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Falls Church
country: United States
facility: Research Site
state: Virginia
city: Darlinghurst
country: Australia
facility: Research Site
state: New South Wales
city: East Sydney
country: Australia
facility: Research Site
state: New South Wales
city: Sydney
country: Australia
facility: Research Site
state: New South Wales
city: Fortitude Valley
country: Australia
facility: Research Site
state: Queensland
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Prahran
country: Australia
facility: Research Site
state: Victoria
city: Antwerp
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Lyon cedex 04
country: France
facility: Research Site
city: Montpellier cedex 5
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Paris Cedex 12
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Modena
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Almada
country: Portugal
facility: Research Site
city: Aveiro
country: Portugal
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Constanta
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
state: Gauteng
city: Westdene
country: South Africa
facility: Research Site
state: Gauteng
city: Bloemfontein
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Geneva 14
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Lugano
country: Switzerland
facility: Research Site
city: Zuerich
country: Switzerland
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.