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

NCT05488431 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 1.0
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 3

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.

Conditions

Dyslipidemias; Cardiovascular Diseases; HIV Infections; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• FDG PET/CT Endpoint

  Change in Target-to-background ratio from baseline to follow-up study at 52 weeks. The main arterial endpoint is the most diseased segment of the index vessel. These findings will be correlated to measurements in the secondary endpoint.

  Baseline and Week 52

Secondary Outcomes (22)

• Total Cholesterol Endpoint

  Baseline, Week 24 and Week 52

• HDL Endpoint

  Baseline, Week 24 and Week 52

• LDL Endpoint

  Baseline, Week 24 and Week 52

• Triglycerides Endpoint

  Baseline, Week 24 and Week 52

• Apolipoprotein B Endpoint

  Baseline, Week 24 and Week 52

Other Outcomes (3)

• Coronary CTA Non-calcified Plaque Endpoint

  Baseline and Week 52

• Coronary CTA High-risk Plaque Endpoint

  Baseline and Week 52

• Coronary CTA Coronary Plaque Incidence Endpoint

  Baseline and Week 52

Study Arms (2)

Bempedoic acid (BA)

EXPERIMENTAL

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

Drug: Bempedoic acid

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Bempedoic acid 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).

Also known as: BA

Bempedoic acid (BA)

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: collaborator
• Massachusetts General Hospital: collaborator
• Priscilla Hsue, MD: lead

Study Sites (3)

UCLA Center for Clinical AIDS Research and Education (CARE)

Los Angeles, California, 90095, United States

RECRUITING

San Francisco General Hospital

San Francisco, California, 94110, United States

RECRUITING

UT Health Houston

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Dyslipidemias; Cardiovascular Diseases; HIV Infections; Atherosclerosis

Interventions

8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Priscilla Hsue, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta Levkova

CONTACT

628-206-8037; marta.levkova@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Priscilla Hsue

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: August 4, 2022
• Study Start: March 1, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)