Evolocumab (AMG 145) in HIV & Hyperlipidemia and/or Mixed Dyslipidemia
Research type
Research Study
Full 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
IRAS ID
202235
Contact name
Graeme Moyle
Contact email
Sponsor organisation
Amgen Ltd.
Eudract number
2015-004735-12
Duration of Study in the UK
2 years, 10 months, 5 days
Research summary
Individuals with high cholesterol (hyperlipidemia and mixed dyslipidemia) are at a higher risk of developing coronary heart disease. Hyperlipidemia and mixed dyslipidemia occurs when there is a high level of total cholesterol or low-density lipoprotein cholesterol (LDL cholesterol; “bad” cholesterol) in the blood.
In countries with access to highly active antiretroviral therapy, the prognosis of HIV infection has changed with mortality from acquired immunodeficiency syndrome (AIDS)-related causes declining while non-AIDS related causes, including cardiovascular disease (CVD), have risen. In addition to the increased risk of CVD attributed directly to HIV infection, HIV therapy itself, are also linked to increased CVD risk.
Evolocumab is an investigational protein that binds to a natural protein that is produced by the liver called proprotein convertase subtilisin kexin-type 9 (PCSK9). By attaching to PCSK9, evolocumab is expected to lower the low-density lipoprotein cholesterol (LDL-C) in the blood by allowing the protein already present in the liver (the LDL receptor) to move the LDL-C out of the bloodstream more efficiently. It has been shown that HIV-infected patients have limitations with statin therapy including possible statin resistance, and elevations of PCSK9 are seen in chronic inflammatory states including HIV infection. Treatment with an anti-PCSK9 monoclonal antibody is therefore a plausible target for LDL cholesterol reduction in HIV-infected individuals.
The purpose of this multi-centre, double-blind placebo controlled phase 3b study is to understand the efficacy and safety of evolocumab in HIV-positive subjects with hyperlipidemia and/or mixed dyslipidemia and will recruit approximately 450 participants.
After consenting, participants will enter the screening phase for approximately 4 weeks, following which eligible participants will be randomised to receive investigational product, which will be either placebo or evolocumab 420mg, for a 24 week double-blind treatment period. Subjects who receive a dose of investigational product at week 20 will continue in an open-label period for a further 24 weeks where all participants will receive evolocumab 420mg. The planned duration of involvement for each participant is approximately 56 weeks, including the screening period and end of study visit.
It is anticipated that participants will complete 7 on site study visits. Investigational product will be administered at the study site and also self-administered at home on 10 occasions by the participant. During the study, participants will undergo a number of procedures and assessments, including physical examinations, urine tests, blood tests, and reviews of adverse event and medication use.
The study is funded by the sponsor, Amgen Inc. and will be run at several specialist NHS centres in England.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
16/WM/0285
Date of REC Opinion
28 Jul 2016
REC opinion
Further Information Favourable Opinion