A Clinical Study in Children With Heterozygous Familial Hypercholesterolemia (HeFH) Aged 6 to 17 Treated Once Daily With Bempedoic Acid Oral Dosing (CLEAR Path 1) (CLEAR Path 1)

An Open-Label Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Bempedoic Acid in Pediatric Patients (6 to 17 Years of Age) With Heterozygous Familial Hypercholesterolemia

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

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Bempedoic acid

Detailed Description

Dose-selection based on body weight will be determined for use in pediatric clinical development.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital - Stollery Children's Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Center
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Ecogene-21
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Viborg, Denmark
    • Viborg Regional Hospital
• Germany
  • Frankfurt am Main, Germany
    • Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
  • Hanover, Germany
    • Kinder- und Jugendkrankenhaus AUF DER BULT
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC - Locatie AMC
  • Rotterdam, Netherlands, 3015 G
    • Erasmus MC
• Spain
  • Barcelona, Spain, 8950
    • Hospital Sant Joan de Déu
  • Barcelona, Spain, 8208
    • Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
  • Cadiz, Spain, 11407
    • Hospital Universitario de Jerez de la Frontera
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Galicia
    • A Coruña, Galicia, Spain, 15001
      • Hospital Abente y Lago
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • West Covina, California, United States, 91790
      • Providere Research Inc
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17601
      • Cardiology Care for Children
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah and Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant's parent(s)/guardian(s) must be willing to provide written informed consent and the participant must provide informed assent before any study-specific procedures are performed;
• Participant must be aged 6-17 years old and willing to swallow tablets;
• Participant must weigh at least 16 kilograms (kg);

• Participant must have a diagnosis of HeFH prior to receiving the first dose of study medication at Treatment Visit T1 per Make Early Diagnosis to Prevent Early Deaths project (MEDPED) criteria by meeting at least one of the following clinical criteria:

  1. Documented diagnosis of HeFH determined by positive genetic testing; or
  2. Documented LDL-C or TC meeting one or more of the following criteria:

  i. LDL-C >200 milligrams per deciliter (mg/dL) (5.2 millimole per liter [mmol/L]) or TC >270 mg/dL (7.0 mmol/L), with no first- second- or third-degree relative with documented FH diagnosis (general population); or ii. LDL-C >155 mg/dL (4.0 mmol/L) or TC >220 mg/dL (5.7 mmol/L), and also having a first-degree relative with documented familial hypercholesterolemia (FH) diagnosis; or iii. LDL-C >165 mg/dL (4.3 mmol/L) or TC >230 mg/dL (5.9 mmol/L), and also having a second-degree relative with documented FH diagnosis; or iv. LDL-C >170 mg/dL (4.4 mmol/L) or TC >240 mg/dL (6.2 mmol/L), and also having a third-degree relative with documented FH diagnosis

• Current treatment with approved stable lipid-modifying therapy (LMT), including an optimal dose of statin with or without other LMT(s), at stable dose for at least 4 weeks prior to Treatment Visit T1 (6 weeks for fibrates; however, gemfibrozil is not allowed in participants taking a statin as per coadministration instructions defined in the statin label). Participants must remain on that stable dose throughout the duration of the trial. Optimal dose of statin will be determined by the investigator using their medical judgment and available sources, including the participant's self-reported history of LMT. A participant's optimal dose of statin is defined as meeting one of the following criteria:

  1. the highest approved dose of statin prescribed for the age of the participant based on regional practice or local guidelines; or
  2. less than the highest approved dose of statin, including no statin, prescribed for the age of the participant based on regional practice or local guidelines (including no statin) if: i. the participant has previously taken 2 or more statin therapies at any dose and not able to tolerate or unresponsive due to their mutations (null); or ii. the participant has previously taken 1 or more statin therapies at any dose and is unwilling to attempt another statin at any dose or advised by a physician to not attempt another statin at any dose.
  3. Participant/parent and investigator attestation to the participant's unwillingness to attempt and/or physician advice to not attempt additional statin therapy will be recorded.

Exclusion Criteria:

• Participant has a diagnosis of homozygous familial hypercholesterolemia (HoFH) or compound HeFH;
• Participant has a fasting triglyceride (TG) level ≥400 mg/dL (4.5 mmol/L);
• Participant has uncontrolled hypothyroidism, including a value for thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or >1.5 × the upper limit of normal (ULN);

• Participant has liver disease or dysfunction, including:

  1. positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibodies (HCV-AB), or
  2. serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥2 × ULN and/or serum total bilirubin (TB) value ≥2 × ULN. If the serum TB value is ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and, if consistent with Gilbert's disease or if the participant has a history of Gilbert's disease, the participant may be enrolled in the study.
• Participant has renal dysfunction or glomerulonephritis, including an estimated glomerular filtration rate (eGFR) <75 milliliters/minute/1.73 square meter (mL/min/1.73 m^2).

Other protocol defined inclusion and exclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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.	Drug: Bempedoic acid; Once daily oral dosing with oral tablets.; Other Names: ETC-1002
Experimental: Cohort 2; 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.	Drug: Bempedoic acid; Once daily oral dosing with oral tablets.; Other Names: ETC-1002
Experimental: Cohort 3; Participants at greater than 60 kg body weight at screening receiving once daily 180 mg bempedoic acid for 8 weeks.	Drug: Bempedoic acid; Once daily oral dosing with oral tablets.; Other Names: ETC-1002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Trough Plasma Concentration of ETC-1002 Following 8 Weeks of Steady State Dosing of Bempedoic Acid	Blood plasma samples were collected and analyzed to determine the plasma trough concentration of ETC-1002 following 8 weeks of steady-state dosing of bempedoic acid. The data presented here is for participants who received tablet formulation only.	Week 8 pre-dose
Model-based Steady State Area Under the Concentration-time Curve Over 24 Hours (AUC,24ss) of ETC-1002	Blood plasma samples were collected and analyzed to determine the AUC,24ss of ETC-1002 over 24 hours. The data presented here is for participants who received tablet formulation only.	24 hours
Model-based Steady State Average Plasma Concentration (Cavg,ss) of ETC-1002	Blood plasma samples were collected and analyzed to determine the Cavg,ss of ETC-1002. Cavg was calculated by empirical Bayesian estimated pediatric exposure over 24 hours divided by 24 (AUC24hr.ss / 24). The data presented here is for participants who received tablet formulation only.	Week 8, 24 hours post-dose at steady state
Model-based Steady State Maximum Plasma Concentration (Cmax,ss) of ETC-1002	Blood plasma samples were collected and analyzed to determine the Cmax,ss of ETC-1002. The data presented here is for participants who received tablet formulation only.	Day 1: 1-hour and 4 hours post-dose; Week 4 pre-dose; Week 8 pre-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Trough Plasma Concentration of ESP15228	Blood plasma samples were collected and analyzed to determine the trough plasma concentration of active metabolite ESP15228 following 8 weeks of steady-state dosing of bempedoic acid. The data presented here is for participants who received tablet formulation only.	Week 8 pre-dose
Observed Plasma Concentration at 4 Hours (C4hr) of ETC-1002	Blood plasma samples were collected and analyzed to determine the trough plasma concentration of ETC-1002 4 hours post-dose. The data presented here is for participants who received tablet formulation only.	Day 1: 4 hours post-dose
Observed C4hr of ESP15228	Blood plasma samples were collected and analyzed to determine the trough plasma concentration of active metabolite ESP15228 4 hours post-dose on Day 1. The data presented here is for participants who received tablet formulation only.	Day 1: 4 hours post-dose
Simulated Percent Change From Baseline in Exposure/ Low-Density Lipoprotein-Cholesterol (LDL-C)	Blood samples were collected for the analysis of and exposure/LDL-C-lowering response relationship.	Baseline and Week 12
Observed Percent Change From Baseline in LDL-C	Blood samples were collected for analysis of LDL-C levels. Baseline is defined as the last assessment measurements before the first dose of investigational medical product (IMP). Percent change from baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Observed Absolute Change From Baseline in LDL-C (mg/dl)	Blood samples were collected for analysis of LDL-C levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from baseline is defined as post- dose visit value minus baseline value. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Observed Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Blood samples were collected for analysis of Non-HDL-C levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Observed Absolute Change From Baseline in Non-HDL-C (mg/dL)	Blood samples were collected for analysis of Non-HDL-C levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from Baseline is defined as post- dose visit value minus Baseline value. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Observed Percent Change From Baseline in Total Cholesterol (TC)	Blood samples were collected for analysis of total cholesterol levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Observed Absolute Change From Baseline in TC (mg/dL)	Blood samples were collected for analysis of TC levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from Baseline is defined as post- dose visit value minus Baseline value. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Observed Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)	Blood samples were collected for analysis of hsCRP. Baseline is defined as the last assessment measurements before the first dose of IMP. Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Observed Absolute Change From Baseline in hsCRP (mg/L)	Blood samples were collected for analysis of hsCRP levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from Baseline is defined as post- dose visit value minus Baseline value. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.	Baseline and 8 Weeks post-treatment
Acceptability of Taste of Liquid Formulation Using a Dosing Acceptability Questionnaire	Participant acceptance is defined as the overall ability of the participant to use a medicine as intended. The acceptability of overall flavor of IMP was recorded using a dosing acceptability questionnaire, where participants were asked 'Yes' or 'No', whether the flavor of the medication was acceptable. At Week 8 (Phone) participants in cohorts 1 and 2 were contacted by phone to collect questionnaire information. The number of participants who have responded at each time point have been presented.	Days 1 and 2; Weeks 2, 4, 8, 8 (Phone), 10, 12, and 16
Acceptability of Ease of Swallowing Tablet Formulation Using a Dosing Acceptability Questionnaire	Participant acceptance is defined as the overall ability of the participant to use a medicine as intended. Acceptability of ease of swallowing was recorded using a dosing acceptability questionnaire where participants were asked if they were able to swallow the entire dose or not, by ticking 'yes' or 'no'. At Week 8 (Phone) participants in cohorts 1 and 2 were contacted by phone to collect questionnaire information. The number of participants who responded at each time point have been presented.	Days 1 and 2; Weeks 2, 4, 8, 8 (Phone), 10, 12, and 16
Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs	An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A serious AE is an AE occurring during any study phase (i.e., baseline, treatment, washout, or follow-up), and at any dose of the study medication that fulfills one or more of the following: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect, is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.	Up to Week 16

Collaborators and Investigators

• Sponsor: Esperion Therapeutics, Inc.
• Investigators: Study Director: Jeffrey C Hanselman, MS, Esperion Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Actual): June 4, 2025
• Study Completion (Actual): June 4, 2025

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 15, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pediatric; ETC-1002; Adenosine triphosphate citrate lyase; Heterozygous familial hypercholesterolemia; Bempedoic acid; Low-density lipoprotein cholesterol (LDL-cholesterol)
• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: 1002-041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

The Investigator must ensure that the participant's confidentiality is maintained. The names and identities of all research participants will be kept in strict confidence and will not appear on eCRFs or other records that are provided to or retained by the Sponsor (or designee). If a participant's name appears on any document, it must be redacted and replaced with the participant identifier before a copy of the document is supplied to the Sponsor (or designee). The ICF must include appropriate statements explaining that participant data will be confidential and the actions that will be taken to ensure participant confidentiality.

Any other confidentiality requirements specified by the site, IRB or IEC, or national or local regulations will be adhered to and detailed appropriately in the ICF.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No