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)

Esperion Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Hypercholesterolemia

Treatments: Drug: Bempedoic acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT05694260

1002-041

Details and patient eligibility

About

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

Full description

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

Enrollment: 54 estimated patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 3 patient groups

Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Bempedoic acid

Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: Bempedoic acid

Cohort 3

Experimental group

Description:

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

Treatment:

Drug: Bempedoic acid