Clinical trial NCT05694260: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: Pediatric
Heterozygous familial hypercholesterolemia
Low-density lipoprotein cholesterol (LDL-cholesterol)
Bempedoic acid
ETC-1002
Adenosine triphosphate citrate lyase
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-23
Enrollment: 54
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Plasma trough concentration of ETC-1002
timeFrame: 8 weeks of steady-state dosing
measure: Area under the plasma concentration-time curve (AUC,ss) of ETC-1002
timeFrame: 8 weeks of steady-state dosing
measure: Average plasma concentration (Cavg,ss) of ETC-1002
timeFrame: 8 weeks of steady-state dosing
measure: Maximum plasma concentration (Cmax,ss) of ETC-1002
timeFrame: 8 weeks of steady-state dosing
Secondary outcomes:
measure: Plasma trough concentration of ESP15228
timeFrame: 8 weeks of steady-state dosing
measure: Plasma concentration at 4 hours (C4hr) of ETC-1002
timeFrame: Day 1
measure: C4hr of ESP15228
timeFrame: Day 1
measure: Exposure/LDL-C response relationship
timeFrame: 8 weeks of steady-state dosing
measure: Percent change from Baseline in low-density lipoprotein cholesterol (LDL-C)
timeFrame: Baseline and at Weeks 8 and 16
measure: Absolute change from Baseline in LDL-C
timeFrame: Baseline and at Weeks 8 and 16
measure: Percent change from Baseline in non-high-density lipoprotein cholesterol (non-HDL-C)
timeFrame: Baseline and at Weeks 8 and 16
measure: Absolute change from Baseline in non-HDL-C
timeFrame: Baseline and at Weeks 8 and 16
measure: Percent change from Baseline in total cholesterol (TC)
timeFrame: Baseline and at Weeks 8 and 16
measure: Absolute change from Baseline in TC
timeFrame: Baseline and at Weeks 8 and 16
measure: Percent change from Baseline in high-sensitivity C-reactive protein (hsCRP)
timeFrame: Baseline and at Weeks 8 and 16
measure: Absolute change from Baseline in hsCRP
timeFrame: Baseline and at Weeks 8 and 16
measure: Acceptability of taste using a dosing acceptability questionnaire
timeFrame: Up to Week 16
measure: Acceptability of ease of swallowing using a dosing acceptability questionnaire
timeFrame: Up to Week 16
measure: Number of participants reporting Serious adverse events (SAEs) and non-SAEs
timeFrame: Up to Week 16
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: West Covina
country: United States
facility: Providere Research Inc
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research
state: Missouri
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Lancaster
country: United States
facility: Cardiology Care for Children
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah and Primary Children's Hospital
state: Utah
city: Edmonton
country: Canada
facility: University of Alberta Hospital - Stollery Children's Hospital
state: Alberta
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Viborg
country: Denmark
facility: Viborg Regional Hospital
city: Frankfurt am Main
country: Germany
facility: Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
city: Hannover
country: Germany
facility: Kinder- und Jugendkrankenhaus AUF DER BULT
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie AMC
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: La Coruña
country: Spain
facility: Hospital Abente y Lago
state: Galicia
city: Barcelona
country: Spain
facility: Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Cadiz
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
References: