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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection

Intervention / Treatment
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* Drug: Evolocumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-Blind Placebo SC QM/Open-Label Evolocumab 420 mg SC QM<br>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<br>* Dose of subcutaneous evolocumab QM<br>* Other names: AMG 145;Drug: Placebo<br>* Dose of matching placebo QM<br>|
| Placebo Comparator: Double-Blind Evolocumab 420 mg SC QM/Open-Label Evolocumab 420 mg SC QM<br>Double-blind evolocumab SC injection QM for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks. | Drug: Evolocumab<br>* Dose of subcutaneous evolocumab QM<br>* Other names: AMG 145;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 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 | 
| Percent Change From Baseline in Apolipoprotein B (ApoB) 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 | 
| Percent Change From Baseline in Total Cholesterol (TC) 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 | 
| Percent Change From Baseline in Lipoprotein(a) (Lp[a]) 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 | 
| Percent Change From Baseline in Triglycerides 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 | 
| Percent Change From Baseline in HDL-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.) | Bseline, Week 24 | 
| Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viral load, Dyslipidemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9), Inhibition, HIV infection, Cluster of differentiation, Hyperlipidemia