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

NCT ID: NCT05488431

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-01
• Study Completion Date: 2028-03-01

Brief 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 and UCLA. Collaborators at Massachusetts General Hospital (MGH) will serve as the core facility for imaging.

Detailed Description

Persons living with HIV infection (PLWH) have a 2-fold higher risk of myocardial infarction and are twice as likely to develop cardiovascular disease accounting for a significant global burden of disease. While the mechanism underlying this excess risk remains poorly understood, studies demonstrate that atherosclerosis in the setting of HIV is distinct and characterized by heightened arterial inflammation as assessed by FDG-PET/CT. HIV and antiretroviral medication can worsen cardiometabolic parameters. Thus a therapeutic strategy that can lower lipids, inflammation, and improve glycemic parameters may be even more advantageous in HIV. Bempedoic acid (BA, an inhibitor of ATP citrate lyase), is safely tolerated, significantly lowers LDL-C and inflammatory markers (on top of statin therapy), and is FDA approved for individuals with heterozygous familial hypercholesterolemia or with established ASCVD who require additional LDL-C lowering. Additionally, BA has a protective effect on glycemic parameters and may reduce adiposity. Given the key role of lipids and inflammation in atherosclerosis in HIV, the purpose of this proof-of-concept mechanistic trial is to evaluate the impact of BA on the biology of HIV-associated atherosclerosis. This is a randomized placebo controlled study of effectively treated PLWH aged 40 years and older with either known CVD or 1 CVD risk factor to study the effect of BA on arterial inflammation (assessed by FDG-PET/CT), lipid levels, biomarkers of inflammatory/immune activation, cardiometabolic indices, and non-calcified plaque in the coronary arteries (assessed by CCTA). This multicenter trial will include PLWH enrolled at UCSF and UCLA. Long term collaborators at MGH will serve as the core facility for the imaging end-points. There are three specific aims for the: Cholesterol and inflammation Lowering via BEmpedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial): Aim 1: To determine whether BA can safely reduce arterial inflammation including carotid plaque as assessed by FDG-PET/CT; Aim 2: To determine whether BA improves cardiometabolic measures (lipid, inflammatory, glycemic and adipose parameters) among PLWH. Exploratory objectives will be to assess BA's effect (vs. placebo) on glycemic as well as adipose tissue measures (HbA1c, HOMA IR, and adipose tissue volumes); Aim 3: To evaluate the impact of BA on non-calcified coronary plaque volume as measured by coronary CT angiography (CCTA).

Conditions

Dyslipidemias; Cardiovascular Diseases; HIV Infections; Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Bempedoic acid (BA)

Patients randomized into the BA arm will receive 180 mg BA administered orally once daily without food for 52 weeks.

Group Type: EXPERIMENTAL

Bempedoic acid

Intervention Type: DRUG

Bempedoic Acid is an oral first-in-class small molecular adenosine triphosphate (ATP)-citrate lyase (ACL) inhibitor which lowers LDL-C by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Inhibition of ACL by bempedoyl-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of LDL receptors and concomitant suppression of hepatic fatty acid biosynthesis. BA has been studied in \>4300 individuals and is currently being studied in \>14,000 individuals in CLEAR Outcomes (NCT02993406).

Placebo

Patients randomized into the placebo arm will receive 180 mg placebo administered orally once daily without food for 52 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

Bempedoic acid

Bempedoic Acid is an oral first-in-class small molecular adenosine triphosphate (ATP)-citrate lyase (ACL) inhibitor which lowers LDL-C by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Inhibition of ACL by bempedoyl-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of LDL receptors and concomitant suppression of hepatic fatty acid biosynthesis. BA has been studied in \>4300 individuals and is currently being studied in \>14,000 individuals in CLEAR Outcomes (NCT02993406).

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Other Intervention Names

BA

Eligibility 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 ≥ 50 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)
• 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Priscilla Hsue, MD

OTHER

Sponsor Role: lead

Responsible Party

Priscilla Hsue, MD

Dr. Priscilla Hsue

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Priscilla Hsue, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

UCLA Center for Clinical AIDS Research and Education (CARE)

Los Angeles, California, United States

Site Status: RECRUITING

San Francisco General Hospital

San Francisco, California, United States

Site Status: RECRUITING

UT Health Houston

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marta Levkova

Role: CONTACT

marta.levkova@ucsf.edu

628-206-8037

Facility Contacts

Aleen Khodabakhshian

Role: primary

akhodabakhshian@mednet.ucla.edu

(310) 557-3798

Marta Levkova

Role: primary

Marta.levkova@ucsf.edu

628-206-8037

Brenda Lastra Bojorguez

Role: primary

brenda.lastrabojorquez@uth.tmc.edu

Other Identifiers

1.0

Identifier Type: -

Identifier Source: org_study_id