A Phase 2 Clinical Study in Children With HeFH Aged 6 to 17 Treated Once Daily With Bempedoic Acid Oral Dosing (CLEAR Path 1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Esperion Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

12 Mar 2025 → 4 Jun 2025

Decision date (initial)

2024-09-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Esperion Therapeutics, Inc.

External identifiers

EU CT number

2024-515864-30-00

EudraCT number

2018-004084-31

WHO UTN

U1111-1309-9693

ClinicalTrials.gov

NCT05694260

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic

To assess the pharmacokinetics (PK) of bempedoic acid (ETC-1002) in pediatric patients (6 to 17 years of age) with HeFH treated for 8 weeks.

Secondary objectives 5

1. To assess the PK of ESP15228 (active metabolite)
2. To assess bempedoic acid exposure/LDL-C-lowering response relationship
3. To assess the absolute and percent change from baseline to Weeks 8 and 16 inLDL-C, total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C)and high-sensitivity C-reactive protein (hsCRP)
4. To monitor the acceptability (taste and ease of swallowing) of the age appropriate formulations
5. To assess the safety and tolerability of bempedoic acid in pediatric patients withHeFH treated with escalating, multiple oral doses of bempedoic acid based on bodyweight for 8 and 16 weeks

Conditions and MedDRA coding

Heterozygous familial hypercholesterolemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. The patient's parent(s)/guardian(s) must be willing to provide written informed consent and the patient must provide informed assent before any study-specific procedures are performed
2. The patient must be aged 6-17 years old and willing to swallow tablets
3. The patient must weigh at least 16 kg
4. The patient must have a diagnosis of HeFH prior to receiving the first dose of study medication at Treatment Visit T1 per MEDPED (Make Early Diagnosis to Prevent Early Deaths project) criteria by meeting at least one of the following clinical criteria: (a.) Documented diagnosis of HeFH determined by positive genetic testing; or (b.) Documented LDL-C or TC meeting one or more of the following criteria: (i.) LDL-C >200 mg/dL (5.2 mmol/L) or total cholesterol (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
5. Current treatment with approved stable LMTs, 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 patients taking a statin as per co-administration instructions defined in the statin label) Patient 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 patient’s self-reported history of LMT. A patient’s optimal dose of statin is defined as meeting one of the following criteria: a. the highest approved dose of statin prescribed for the age of the patient based on regional practice or local guidelines; or b. less than the highest approved dose of statin, including no statin, prescribed for the age of the patient based on regional practice or local guidelines (including no statin) if: i. the patient 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 patient 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. Patient/parent and investigator attestation to the patient’s unwillingness to attempt and/or physician advice to not attempt additional statin therapy will be recorded.
6. The patient must have a fasting LDL-C level ≥130 mg/dL (3.4 mmol/L) while on sstable LMT as defined in inclusion criteria 5
7. The patient may be male or female. Females must not be pregnant (or planning to become pregnant within 30 days after the last dose of investigational medicinal product [IMP]) breastfeeding and must be sexually inactive or willing to use 1 acceptable method of birth control. The minimal requirement for use of acceptable contraception is from the time the informed consent form (ICF) is signed, during the study period, and for at least 30 days after the last dose of IMP. Acceptable methods of birth control include: a. placement of an intrauterine device (IUD) with or without hormones, b. established use of oral, implanted, topical, or injectable, or hormonal method of contraception associated with inhibition of ovulation, or c. barrier methods, including condom or occlusive cap with spermicidal foam or spermicidal jelly, There are no protocol-specific birth control requirements for males who have partners that can become pregnant.

Exclusion criteria 19

1. The patient has a diagnosis of HoFH or compound HeFH;
2. The patient has a fasting triglyceride (TG) level ≥400 mg/dL (4.5 mmol/L)
3. The patient 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)
4. The patient has liver disease or dysfunction, including: a. positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibodies (HCV-AB), or b. serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥2 × ULN and/or serum total bilirubin (TB) value ≥2 × ULN
5. The patient has renal dysfunction or glomerulonephritis, including an estimated glomerular filtration rate (eGFR) <75 mL/min/1.73 m2 (as determined by the central laboratory using the Revised ["Bedside"] Schwartz formula)
6. The patient has Stage 2 hypertension (based on gender, age and height; see Appendix 4)
7. The patient has a gastrointestinal condition that may affect drug absorption
8. The patient has a history of hematologic or coagulation disorders, anemia, or a hemoglobin (Hgb) level <11.5 g/dL
9. The patient has type 1 or type 2 diabetes, or newly diagnosed impaired glucose tolerance (within 3 months of Screening)
10. The patient had an active malignancy, including those requiring surgery, chemotherapy, and/or radiation, in the past 5 years. Nonmetastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ are allowed
11. The patient has an unexplained (ie, not associated with recent trauma or physically strenuous activity) serum creatine kinase (CK) value >3 × ULN at any time before randomization. Patients with an explained elevation in serum CK must have single repeat serum CK value ≤3 × ULN before enrollment
12. The patient has a history of drug or alcohol abuse within the last 2 years or is unwilling to refrain from alcohol consumption for the duration of the study, or uses any illicit drugs, or has a history of amphetamine or derivatives abuse or cocaine abuse. Patients who are using amphetamine derivatives prescribed by and who are under the care of a health care practitioner can be enrolled after evaluation by the Investigator
13. The patient has donated blood, undergone multiple blood draws in a clinical study, experienced major trauma, received a blood transfusion, or undergone surgery, with or without blood loss, within 30 days before enrollment
14. The patient has used any experimental or investigational drugs within 30 days before screening and throughout the trial
15. The patient has previously participated in a clinical study of bempedoic acid
16. The patient is taking any of the following medications or therapies, except as indicated below: a. Mipomersen or lomitapide (current or within 6 months of Screening). b.PCKS9 inhibitors including evolocumab or alirocumab (current or within 3 months of Screening). c. Lipid apheresis (current or within 8 weeks of Screening or intends to have lipidapheresis treatments throughout the trial). d. Systemic corticosteroids (current or within 4 weeks prior to enrollment; topical and inhaled corticosteroids are allowed). e. Red yeast rice extract (also known as monascus purpureus extract or Cholestin) containing products (current or within 4 weeks of Screening); f. Lipid altering nutritional supplements including berberine, psyllium (Metamucil®),green tea extract, sitostanol (found in oral nutritional supplements and some margarines, such as Benecol), beta-sitosterol(found in oral nutritional supplements and some margarines, such as Promise Activ), pantothine and policosanol (current or within 4 weeks of Screening); g. Bile acid sequestrants, fibrates, omega 3 fatty acids, or niacin, unless the dose has been stable for ≥6 weeks and will remain stable throughout the trial. h. Simvastatin >20 mg or pravastatin >40 mg (current or within 4 weeks of Screening).
17. The patient has a history or evidence of any other clinically significant condition, or planned or expected procedure that in the opinion of the Investigator, may compromise the patient's safety or ability to complete the study
18. The patient has a situational (ie, geographical) finding that, in the Investigator's opinion, may compromise the patient's safety or ability to complete the study
19. The patient is an employee or contractor of the facility that is conducting the study or is a family member of the Investigator, subInvestigator, or any Sponsor personnel

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Observed trough plasma concentration of ETC-1002 following 8 weeks of steady-state dosing of bempedoic acid
2. Model-based PK parameters including steady-state estimates of: −area under the plasma concentration-time curve (AUCss), −average plasma concentration (Cavg,ss) and −maximum plasma concentration (Cmax,ss)

Secondary endpoints 5

1. Observed trough plasma concentration of ESP15228 (active metabolite) following 8 weeks of steady-state dosing of bempedoic acid
2. Plasma concentration at 4 hours (C4hr) of ETC-1002 and ESP15228 following first dose
3. ETC-1002 dose and exposure/LDL-C-lowering response relationship
4. Percent and absolute from baseline to Weeks 8 and 16 in LDL-C, TC, non-HDL-C, and hsCRP
5. Evaluation of acceptability (taste and ease of swallowing) of the age appropriate formulations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Esperion Therapeutics Inc.

Sponsor organisation

Esperion Therapeutics Inc.

Address

3891 Ranchero Drive Suite 150

City

Ann Arbor

Postcode

48108-2837

Country

United States

Scientific contact point

Organisation

Esperion Therapeutics Inc.

Contact name

Esperion Medical Information

Public contact point

Organisation

Esperion Therapeutics Inc.

Contact name

Esperion Medical Information

Third parties 7

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications