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

Amgen

Status and phase: Completed; Phase 3

Conditions: Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection

Treatments: Drug: Placebo; Drug: Evolocumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02833844

20130286

2015-004735-12 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 467 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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467 participants in 2 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Evolocumab

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

Placebo Comparator group

Description:

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

Treatment:

Drug: Evolocumab