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

Phase 3

Completed

Conditions: Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection

Interventions: Drug: Evolocumab
Drug: Placebo

Registration Number: NCT02833844

Lead Sponsor: Amgen

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 467

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Double-Blind Placebo SC QM/Open-Label Evolocumab 420 mg SC QM	Placebo	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.
Double-Blind Placebo SC QM/Open-Label Evolocumab 420 mg SC QM	Evolocumab	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.
Double-Blind Evolocumab 420 mg SC QM/Open-Label Evolocumab 420 mg SC QM	Evolocumab	Double-blind evolocumab SC injection QM for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in LDL-C at Week 24	Baseline, 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.)

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in LDL-C at Week 24	Baseline, 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.)
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	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.)
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24	Baseline, 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.)
Percent Change From Baseline in Total Cholesterol (TC) at Week 24	Baseline, 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.)
Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24	Baseline, 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.)
Percent Change From Baseline in Triglycerides at Week 24	Baseline, 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.)
Percent Change From Baseline in HDL-C at Week 24	Bseline, 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.)
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24	Baseline, 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.)