Bempedoic Acid for High Cholesterol in Children

(CLEAR Path 1 Trial)

No longer recruiting at 30 trial locations

Overseen By Esperion Medical Information

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Esperion Therapeutics, Inc.

Must be taking: Statins

Must not be taking: Gemfibrozil

Disqualifiers: HoFH, Triglycerides, Hypothyroidism, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of bempedoic acid in managing high cholesterol in children with heterozygous familial hypercholesterolemia (HeFH), a genetic condition that causes elevated cholesterol levels. Researchers aim to understand the body's response to different doses of the medication and assess its safety in children aged 6 to 17. Participants will be divided into groups based on weight and will receive varying doses of the treatment. The trial seeks children with HeFH who are on stable cholesterol medication and have a history of high cholesterol affecting their daily life. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

Participants must continue taking their current stable lipid-modifying therapy (like statins) at the same dose throughout the trial.

Is there any evidence suggesting that bempedoic acid is likely to be safe for children?

Research shows that bempedoic acid lowers bad cholesterol levels. It is approved for adults, but its safety for children remains under study. Clear information on how children handle bempedoic acid is not yet available. Researchers are still determining its safety and potential reactions in children.

As a Phase 2 trial, scientists are collecting data on safety and side effects in children. Earlier phase trials typically focus on understanding a treatment's safety, so participating in this trial helps researchers learn more about how bempedoic acid works in children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high cholesterol?

Bempedoic acid is unique because it offers a new approach to lowering high cholesterol by targeting a specific enzyme involved in cholesterol synthesis, which is different from commonly used treatments like statins. Unlike statins, bempedoic acid works without affecting muscles, potentially reducing side effects such as muscle pain. Researchers are excited because this could be a safer option for children who need cholesterol management, providing a tailored approach based on body weight.

What evidence suggests that bempedoic acid might be an effective treatment for high cholesterol in children?

Research shows that bempedoic acid, which participants in this trial will receive, effectively lowers LDL cholesterol, often called "bad" cholesterol. Earlier studies demonstrated a reduction in LDL cholesterol by 17 to 28%. When combined with another treatment, ezetimibe, it lowered LDL levels by up to 38%. These studies also found that bempedoic acid is generally safe for long-term use, making it a promising option for managing high cholesterol, including in children with HeFH, a genetic condition that causes high cholesterol. ^{5 6 7 8 9}

Who Is on the Research Team?

Michael Louie, MD

Principal Investigator

Esperion Therapeutics, Inc.

Jeffrey C Hanselman, MS

Principal Investigator

Esperion Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for children aged 6-17 with HeFH (a genetic cholesterol disorder) who have high LDL cholesterol levels despite taking other lipid-modifying medications. They must not have diabetes, extremely high triglycerides, or be pregnant or breastfeeding.

Inclusion Criteria

Your "bad" cholesterol (LDL-C) level is higher than 130 mg/dL after not eating for a while.

I am between 6 and 17 years old.

I am on a stable treatment for my cholesterol.

Exclusion Criteria

I have diabetes or my blood sugar levels are higher than normal.

Your fasting triglyceride level is 400 mg/dL (4.5 mmol/L) or higher.

I am currently pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bempedoic acid once daily with dose adjustments based on body weight for a total of 16 weeks

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bempedoic acid

Trial Overview

The study tests the effects of bempedoic acid, a medication intended to lower cholesterol levels in pediatric patients with HeFH. It's given once daily and researchers will monitor how it's processed by the body and its impact on cholesterol.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 1 Intervention

Participants at greater than 60 kg body weight at screening receiving once daily 180 mg bempedoic acid for 8 weeks.

Group II: Cohort 2 Experimental Treatment 1 Intervention

Participants at 30 to 60 kg body weight at screening receiving once daily120 mg bempedoic acid for 8 weeks followed by 150 mg bempedoic acid for 8 weeks.

Group III: Cohort 1 Experimental Treatment 1 Intervention

Participants at 16 to \<30 kilograms (kg) body weight at screening receiving once daily 60 milligrams (mg) bempedoic acid for 8 weeks followed by 90 mg bempedoic acid for 8 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?

Esperion Therapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

21,900+

Founded

2008

Headquarters

Ann Arbor, USA

Known For

Cholesterol Therapies

Top Products

NEXLETOL, NEXLIZET, NILEMDO, NUSTENDI

Published Research Related to This Trial

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]

Bempedoic acid effectively lowers LDL-cholesterol levels by selectively inhibiting cholesterol production in the liver, showing complementary effects when used with ezetimibe without increasing side effects.

It is particularly beneficial for patients at higher risk of cardiovascular events, including those with impaired glucose metabolism, the elderly, and individuals with a history of acute coronary syndrome or familial hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Opportunities and perspectives for bempedoic acid use in clinical practice]. Di Fusco, SA., Scicchitano, P., Colivicchi, F.[2021]

Bempedoic acid is a promising oral medication that lowers cholesterol without causing muscle-related side effects, making it suitable for patients who cannot tolerate statins due to muscle symptoms.

The CLEAR Outcomes trial, involving 14,014 patients with a history of cardiovascular disease and statin intolerance, aims to assess whether bempedoic acid can reduce serious cardiovascular events over a treatment period of at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance. Nicholls, S., Lincoff, AM., Bays, HE., et al.[2021]

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]

Bempedoic acid is an oral medication that effectively lowers low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) and those with heterozygous familial hypercholesterolemia (HeFH), as shown in pooled data from phase III trials involving multiple patients.

It is particularly beneficial for individuals who cannot tolerate statins or require additional LDL-C lowering, and ongoing trials like CLEAR Outcomes will further clarify its role in non-statin lipid-lowering therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside. Agarwala, A., Quispe, R., Goldberg, AC., et al.[2021]

Bempedoic acid significantly lowers various cholesterol levels, including total cholesterol and low-density lipoprotein (LDL) cholesterol, with a large study involving 3,788 participants across 10 randomized controlled trials.

While bempedoic acid has a favorable effect on lipid profiles, it is associated with some risks, such as elevated liver enzymes and uric acid levels, but it may reduce the risk of new or worsening diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis. Cicero, AFG., Fogacci, F., Hernandez, AV., et al.[2020]

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]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05694260

NCT05694260 | A Clinical Study in Children With ...

Multiple-dose study to measure pharmacokinetics, pharmacodynamics and safety of bempedoic acid in pediatric participants 6 to 17 years of age with HeFH.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8637781/

Novel therapeutic targets and agents for pediatric ...

Overall, it lowered LDL-C levels by 15–25% when used alone and up to 38% when combined with ezetimibe. In one of the pivotal studies, patients who received ...

3.

esperion.com

esperion.com/news-releases/news-release-details/esperion-aligns-us-food-and-drug-administration-initiate-phase-3

Esperion Aligns with U.S. Food and Drug Administration to ...

Esperion Aligns with U.S. Food and Drug Administration to Initiate Phase 3 Clinical Trials of Bempedoic Acid in Pediatric Heterozygous and ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0002914922003228

Long-Term Safety and Efficacy of Bempedoic Acid in ...

In conclusion, bempedoic acid was generally well tolerated and demonstrated sustained efficacy with up to 2.5 years of continuous treatment. Bempedoic acid ...

5.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2215024

Bempedoic Acid and Cardiovascular Outcomes in Statin ...

In several studies, bempedoic acid reduced the level of LDL cholesterol by 17 to 28%, a finding that, in 2020, prompted its approval by the Food ...

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/bempedoic-acid-oral-route/description/drg-20484223

Bempedoic acid (oral route) - Side effects & dosage

Pediatric. Appropriate studies have not been performed on the relationship of age to the effects of bempedoic acid in the pediatric population.

7.

ema.europa.eu

ema.europa.eu/en/documents/product-information/nilemdo-epar-product-information_en.pdf

Nilemdo, INN-bempedoic acid - EMA

Paediatric population. The safety and efficacy of Nilemdo in children aged less than 18 years have not yet been established. No data are available. Method of ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/211616s012s013lbl.pdf

nexletol - accessdata.fda.gov

It is not known if NEXLETOL is safe and effective in children. Do not take NEXLETOL if you are allergic to bempedoic acid or any of the ingredients in. NEXLETOL ...

9.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK594232/

Bempedoic Acid - StatPearls - NCBI Bookshelf

Bempedoic acid is a lipid-lowering agent pivotal in managing patients with elevated low-density lipoprotein cholesterol (LDL-C) levels.