Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia
Condition: Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection
MeSH terms: HIV Infections; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias
Intervention: Evolocumab; Placebo
Intervention description: Dose of subcutaneous evolocumab QM; Dose of matching placebo QM
Intervention MeSH terms: Evolocumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 467.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hyperlipidemia; Dyslipidemia; Proprotein convertase subtilisin/kexin type 9 (PCSK9); Inhibition; HIV infection; Cluster of differentiation; Viral load

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.