Cholesterol and Inflammation Lowering Via Bempedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial)

• Status: Not yet recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomized placebo-controlled study in treated and suppressed HIV-infected individuals aged ≥40 years with either known CVD or 1 CVD risk factor to study the effect of Bempedoic acid (BA) on safety, arterial inflammation as assessed by FDG-PET/CT, lipids, inflammation, immune activation, cardiometabolic indices, and non-calcified plaque (NCP) in the coronary arteries (assessed by coronary CT angiography, CCTA). This trial will be enrolled at UCSF, UCLA, and University of Utah; collaborators at Massachusetts General Hospital (MGH) will serve as the core facility for imaging.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Priscilla Hsue, MD
• Collaborators: Massachusetts General Hospital; University of California, Los Angeles; University of Utah
• Treatments: 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid

Criteria

Inclusion Criteria:

• Documented HIV infection

• On continuous antiretroviral therapy and virologically suppressed HIV infection for ≥12 weeks prior to study entry

• CD4 T-cell count ≥ 200 cells/mm3

• Male or female between the ages ≥ 40 years of age

• LDL-C ≥ 100 mg/dL

• Documented cardiovascular disease as defined by: 1. Prior myocardial infarction, 2. Prior cerebrovascular disease, 3. Prior peripheral arterial disease, 4. History of percutaneous coronary intervention, 5. History of coronary artery bypass graft OR 6. Angiographic evidence of >50% stenosis in at least one coronary artery] OR 1 CVD risk factor (T2DM, current smoking, hypertension, dyslipidemia, hsCRP≥2mg/L, family history)

• TBR of >1.6 of the MDS of the carotid/aorta at baseline. This baseline arterial TBR cutoff excludes the rare individual that lacks appreciable arterial inflammation. It is notable that while 5-10% of uninfected individuals will have lower TBRs, it is rare that an HIV infected individual will fall below this range.

• Female subjects must either be of non-childbearing potential (defined as post-menopausal or amenorrhea > 12 months) or agree to use two forms of contraception (one hormonal and one barrier) throughout the study and for at least one month following study completion and have a negative pregnancy test at screening and prior to the first dose of drug.

• Males must use at least one method of contraception throughout the study.

Exclusion Criteria:

• Pregnant/nursing women (as there is no data on bempedoic acid in this setting)

• Diabetes requiring insulin (as insulin treatment alters the uptake of 18FDG)

• Uncontrolled HTN as defined by baseline blood pressure reading of ≥160 mmHg systolic OR ≥100 mmHg diastolic (exclusion criteria in other studies with BA)

• AST/ALT or alkaline phosphatase >2x ULN

• Triglycerides >500 mg/dL at screening

• Cancer within the last 5 years with exception of squamous cell carcinoma and basal cell carcinoma

• Individuals on simvastatin >20mg or pravastatin >40mg. All other dosages and statins will be permitted with close monitoring for myopathies including assessment of CK levels

• Nephrotic syndrome or eGFR <30 mL/min/1.73m2

• Cytopenias which include 1) WBC <3.5 x103/uL 2) Platelet <120 x103/uL 3) ANC <1.5 x103/uL, and absolute lymphocytes <0.8 x 103/uL

• Anemia as fined by Hgb <10 g/dL

• Acute systemic infection within 30 days