Bempedoic Acid for HIV-Related Cardiovascular Disease

Overseen By Marta Levkova

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Priscilla Hsue, MD

Must be taking: Antiretrovirals

Must not be taking: High-dose statins

Disqualifiers: Pregnancy, Insulin-dependent diabetes, Uncontrolled hypertension, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

121 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests bempedoic acid to determine if it can reduce heart-related issues in people with HIV. The focus is on individuals with heart disease or risk factors like high cholesterol or high blood pressure, who are already receiving HIV treatment. Participants will receive either bempedoic acid or a placebo (a pill with no active medicine) to compare effects over a year. People with HIV on stable treatment and with heart disease or a risk factor might be suitable for this trial. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on simvastatin over 20mg or pravastatin over 40mg, you cannot participate. Other statins are allowed with close monitoring.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that bempedoic acid is generally safe and effectively lowers bad cholesterol (LDL-C) while reducing inflammation. This is beneficial for those unable to take statins, a common cholesterol-lowering medication. Studies confirm that bempedoic acid is approved for treating high cholesterol, supporting its safety.

Previous studies demonstrated a good safety record for bempedoic acid, with patients often not experiencing severe side effects. However, some side effects can occur. Consulting a healthcare provider is advisable to understand personal risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cardiovascular disease?

Most treatments for HIV-related cardiovascular disease focus on managing cholesterol levels using statins. But bempedoic acid works differently, targeting an enzyme in the liver called ATP citrate lyase to reduce cholesterol production. Unlike statins, bempedoic acid is designed to lower LDL cholesterol without the muscle-related side effects often associated with those drugs. Researchers are excited about its potential because it offers a new way to help people with HIV manage their cardiovascular risk, particularly for those who can't tolerate statins well.

What evidence suggests that Bempedoic acid might be an effective treatment for HIV-related cardiovascular disease?

Research has shown that bempedoic acid, which participants in this trial may receive, effectively lowers cholesterol, reducing the risk of heart disease. Studies indicate it can reduce LDL cholesterol, often called "bad" cholesterol, by about 39% when combined with other medications. Additionally, bempedoic acid may benefit people with HIV by reducing inflammation related to heart disease. Early data suggest it is well-tolerated and effective for those at high risk of heart problems. These findings suggest that bempedoic acid could help manage heart disease risks in individuals with HIV. ^{4 6 7 8 9}

Who Is on the Research Team?

Priscilla Hsue, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for HIV-infected individuals aged ≥40 with controlled infection and either known cardiovascular disease or one risk factor. Participants must have a CD4 count ≥200 cells/mm3, LDL-C ≥70 mg/dL, and agree to contraception if applicable. Exclusions include pregnancy, certain liver enzyme levels, severe kidney dysfunction, anemia, uncontrolled hypertension, recent acute infections, specific blood cell count abnormalities, very high triglycerides at screening or insulin-treated diabetes.

Inclusion Criteria

Your carotid artery or aorta has too much inflammation. This helps make sure that only people with enough inflammation can join the study.

I will use contraception during the study.

I am 40 years old or older.

Exclusion Criteria

I have not had a serious infection in the last 30 days.

I take insulin for my diabetes.

I am taking simvastatin over 20mg or pravastatin over 40mg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Bempedoic acid or placebo orally once daily for 52 weeks

52 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bempedoic acid
• Placebo

Trial Overview The CLEAR HIV Trial is testing the safety and effects of Bempedoic acid on arterial inflammation (measured by FDG-PET/CT), cholesterol levels (lipids), immune activation and non-calcified plaque in coronary arteries among treated HIV patients with cardiovascular risks. It's a randomized study comparing Bempedoic acid against a placebo.

How Is the Trial Designed?

Group I: Bempedoic acid (BA) Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Bempedoic acid is already approved in United States, European Union for the following indications:

Approved in United States as Nexletol for:

• Hypercholesterolemia in combination with diet and the highest tolerated statin therapy in adults with heterozygous familial hypercholesterolemia, or with established atherosclerotic cardiovascular disease, who need additional lowering of LDL cholesterol

Approved in European Union as Nilemdo for:

• Primary hypercholesterolaemia (heterozygous familial and non familial) or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin; or alone or in combination with other lipid-lowering therapies in patients who are statin intolerant, or for whom a statin is contraindicated

Who Is Running the Clinical Trial?

Priscilla Hsue, MD

Lead Sponsor

Trials

4

Recruited

200+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

In a randomized, placebo-controlled trial involving 26 HIV-infected participants, pentoxifylline (PTX) did not significantly improve endothelial function as measured by flow-mediated dilation (FMD) after 8 weeks of treatment.

PTX was generally well-tolerated but unexpectedly increased the inflammatory biomarker soluble tumor necrosis factor receptor-1 (sTNFRI), indicating a need for further research to effectively reduce inflammation and cardiovascular risk in HIV-infected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial. Gupta, SK., Mi, D., Dubé, MP., et al.[2021]

People living with HIV/AIDS (PLWHA) are at increased risk for cardiovascular disease (CVD) due to endothelial dysfunction, which is influenced by both HIV-1 infection and antiretroviral therapy (ART).

Key factors contributing to endothelial dysfunction include oxidative stress, impaired nitric oxide production, and the effects of specific HIV-1 proteins and antiretroviral drugs, highlighting the need for further research to understand these mechanisms and develop prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular endothelial dysfunction in the wake of HIV and ART. Marincowitz, C., Genis, A., Goswami, N., et al.[2020]

Nevirapine has been shown to be superior to other antiretroviral combinations in improving HDL cholesterol levels in HIV-infected patients, which is important for managing cardiovascular risk.

International cohort studies indicate that nevirapine carries a very limited risk of cardiovascular morbidity, making it a favorable option for patients with cardiovascular risk factors when initiating or substituting antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nevirapine and cardiovascular risk]. Parienti, JJ., Verdon, R.[2013]

Bempedoic acid has been approved in the USA and EU for treating high cholesterol, based on positive results from the phase III CLEAR clinical trial program.

It is available both as a standalone treatment (NEXLETOL® in the USA, Nilemdo® in the EU) and in combination with ezetimibe (NEXLIZET® in the USA, Nustendi® in the EU), highlighting its versatility in managing hypercholesterolaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bempedoic Acid: First Approval. Markham, A.[2022]

In a study of 6,368 patients on first-line HAART, different antiretroviral regimens led to varying elevations in lipid levels over 48 weeks, with boosted protease inhibitors causing significant increases in total cholesterol and triglycerides.

Patients on efavirenz experienced lipid increases similar to those on certain protease inhibitors, but overall, the choice of nucleoside analogues also significantly influenced lipid elevations, highlighting the importance of regimen selection in managing cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of first-line use of nucleoside analogues, efavirenz, and ritonavir-boosted protease inhibitors on lipid levels. Hill, A., Sawyer, W., Gazzard, B.[2022]

In a study of 706 HIV-1 patients over 48 weeks, those on nevirapine (NVP) showed a significantly larger increase in high-density lipoprotein cholesterol (HDL-c) compared to those on efavirenz (EFV), suggesting better lipid profiles with NVP.

NVP treatment resulted in a decrease in the total cholesterol to HDL-c ratio and smaller increases in non-HDL cholesterol and triglycerides compared to EFV, indicating that NVP may lower the risk of coronary heart disease more effectively than EFV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1. van Leth, F., Phanuphak, P., Stroes, E., et al.[2022]

Bempedoic acid at a dose of 180mg has demonstrated both efficacy and safety in phase II and III studies, particularly in patients who cannot tolerate statins.

The drug effectively reduces LDL cholesterol levels when used alone or in combination with statins and ezetimibe, and it may also lower inflammation markers, pending further results from the CV Clear Outcomes trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of bempedoic acid: phase 2 and phase 3 clinical trials. Lekuona, I., Pintó, X.[2021]

Bempedoic acid has been approved as a new treatment for hypercholesterolemia, showing both efficacy and safety in clinical studies, making it a valuable option for managing cholesterol levels.

Unlike statins, bempedoic acid selectively targets the liver, which lowers the risk of muscle-related side effects, providing a safer alternative for patients who may be sensitive to traditional cholesterol-lowering medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[ANMCO Expert opinion: Bempedoic acid place in therapy for hypercholesterolemia management]. Di Fusco, SA., Aquilani, S., Spinelli, A., et al.[2023]

Bempedoic acid is a newly approved treatment for high cholesterol that works by targeting specific pathways to lower low-density lipoprotein (LDL) cholesterol levels, which are linked to atherosclerotic cardiovascular disease.

Clinical evidence supports the use of bempedoic acid in managing hypercholesterolemia, indicating its potential effectiveness in reducing cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated clinical evidence and place in therapy of bempedoic acid for hypercholesterolemia: ANMCO position paper. Colivicchi, F., Di Fusco, SA., Scicchitano, P., et al.[2023]

Bempedoic acid significantly reduces levels of harmful lipids, including LDL cholesterol, non-HDL cholesterol, and apolipoprotein B, based on a meta-analysis of 7 trials involving 3892 patients.

The drug also demonstrates anti-inflammatory effects by significantly lowering high sensitivity C-reactive protein (hsCRP) levels, indicating its potential benefits beyond just lipid lowering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis. Masson, W., Lobo, M., Lavalle-Cobo, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11035727/

Effects of statins beyond lipid-lowering agents in ART- ... Bempedoic acid, a first-in-class non-statin LDL-lowering drug with immune modulatory effects, may further aid PWH in combination with statins. Herein, we ...

2. sti.bmj.com sti.bmj.com/content/101/Suppl_1/A114

P10 Bempedoic acid and evolocumab in people living with ... Our preliminary data indicate that bempedoic acid (alone or with ezetimibe) and evolocumab are well-tolerated in PLH with moderate to very high cardiovascular ...

3. withpower.com withpower.com/trial/phase-3-hiv-infections-11-2022-22014

Bempedoic Acid for HIV-Related Cardiovascular Disease Bempedoic acid has been shown to effectively lower cholesterol levels, which is important because high cholesterol can lead to heart disease. It works similarly ...

4. academic.oup.com academic.oup.com/eurheartjsupp/article/26/Supplement_2/ii115/7674353

LDL TARGET IN PATIENTS WITH HIV AT HIGH ... The use of bempedoic acid, in addition to statin+ezetimibe therapy, or ezetimibe alone in statin–intolerant patients, reduces baseline LDL by 39% and achieves ...

5. natap.org natap.org/2023/HIV/042123_03.htm

Bempedoic Acid and Cardiovascular Outcomes in Statin ... 6 Although we do not have specific cardiovascular outcome data with bempedoic acid monotherapy, it is associated with a reduction in the level of C-reactive ...

6. reporter.nih.gov reporter.nih.gov/search/UcQMuStg50KDjppZ8dZT2Q/project-details/11145571

RePORT RePORTER - National Institutes of Health (NIH) | The purpose of this study is to evaluate the biology of bempedoic acid on atherosclerosis among individuals with treated and suppressed HIV infection. NIH ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05488431

Study Details | NCT05488431 | Cholesterol and ... 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 ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772632023000429

Clinical efficacy and safety outcomes of bempedoic acid ... Based on our analysis the bempedoic acid addition to therapy reduced cardiovascular events in selective patients who are either intolerant to statins or do not ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11221442/

Efficacy and Safety of Bempedoic Acid in Patients With ... Bempedoic acid has also been shown to reduce hsCRP levels. The ongoing CLEAR Outcomes trial, involving a large population of high cardiovascular disease ...