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)

Phase 2

Recruiting

• Conditions: Hypercholesterolemia
• Interventions: Drug: Bempedoic acid

• Registration Number: NCT05694260
• Lead Sponsor: Esperion Therapeutics, Inc.

Brief Summary

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

Detailed Description

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

Study Timeline

• Study Start: 2023-01-12
• Study First Submitted: 2023-01-12
• Study First Submitted QC: 2023-01-12
• Study First Posted: 2023-01-23
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-02-28
• Primary Completion: 2025-06
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Bempedoic acid	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.
Cohort 2	Bempedoic acid	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.
Cohort 3	Bempedoic acid	Participants at greater than 60 kg body weight at screening receiving once daily 180 mg bempedoic acid for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Plasma trough concentration of ETC-1002	8 weeks of steady-state dosing
Area under the plasma concentration-time curve (AUC,ss) of ETC-1002	8 weeks of steady-state dosing
Average plasma concentration (Cavg,ss) of ETC-1002	8 weeks of steady-state dosing
Maximum plasma concentration (Cmax,ss) of ETC-1002	8 weeks of steady-state dosing

Secondary Outcome Measures

Name	Time	Method
Plasma trough concentration of ESP15228	8 weeks of steady-state dosing
Plasma concentration at 4 hours (C4hr) of ETC-1002	Day 1
C4hr of ESP15228	Day 1
Exposure/LDL-C response relationship	8 weeks of steady-state dosing	ETC-1002 dose and exposure/LDL-C-lowering response relationship
Percent change from Baseline in low-density lipoprotein cholesterol (LDL-C)	Baseline and at Weeks 8 and 16
Absolute change from Baseline in LDL-C	Baseline and at Weeks 8 and 16
Percent change from Baseline in non-high-density lipoprotein cholesterol (non-HDL-C)	Baseline and at Weeks 8 and 16
Absolute change from Baseline in non-HDL-C	Baseline and at Weeks 8 and 16
Percent change from Baseline in total cholesterol (TC)	Baseline and at Weeks 8 and 16
Absolute change from Baseline in TC	Baseline and at Weeks 8 and 16
Percent change from Baseline in high-sensitivity C-reactive protein (hsCRP)	Baseline and at Weeks 8 and 16
Absolute change from Baseline in hsCRP	Baseline and at Weeks 8 and 16
Acceptability of taste using a dosing acceptability questionnaire	Up to Week 16
Acceptability of ease of swallowing using a dosing acceptability questionnaire	Up to Week 16
Number of participants reporting Serious adverse events (SAEs) and non-SAEs	Up to Week 16

Trial Locations

Locations (24)

Corporacio Sanitaria Parc Tauli - Hospital de Sabadell; 🇪🇸 Barcelona, Spain

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Providere Research Inc; 🇺🇸 West Covina, California, United States

Excel Medical Clinical Trials, LLC; 🇺🇸 Boca Raton, Florida, United States

Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research; 🇺🇸 Saint Louis, Missouri, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Cardiology Care for Children; 🇺🇸 Lancaster, Pennsylvania, United States

University of Utah and Primary Children's Hospital; 🇺🇸 Salt Lake City, Utah, United States

University of Alberta Hospital - Stollery Children's Hospital; 🇨🇦 Edmonton, Alberta, Canada

McMaster University Medical Center; 🇨🇦 Hamilton, Ontario, Canada

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Viborg Regional Hospital; 🇩🇰 Viborg, Denmark

Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet; 🇩🇪 Frankfurt am Main, Germany

Kinder- und Jugendkrankenhaus AUF DER BULT; 🇩🇪 Hannover, Germany

Amsterdam UMC - Locatie AMC; 🇳🇱 Amsterdam, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Hospital Abente y Lago; 🇪🇸 La Coruña, Galicia, Spain

Hospital Sant Joan de Deu; 🇪🇸 Barcelona, Spain

Hospital Universitario de Jerez de la Frontera; 🇪🇸 Cadiz, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Córdoba, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain