Study to Evaluate the Efficacy and Safety of Lerodalcibep for the Reduction of Cholesterol in Children and Adolescents with Heterozygous Familial Hypercholesterolemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

LIB Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2026-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

LIB Therapeutics, Inc.

External identifiers

EU CT number

2025-524214-28-00

WHO UTN

U1111-1331-9885

ClinicalTrials.gov

NCT07102511

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Others, Pharmacokinetic, Efficacy

To assess the LDL-C reductions at Week 24 with monthly dosing of lerodalcibep 300 mg compared to placebo, in pediatric patients 6 to 17 years of age, with Heterozygous Familial Hypercholesterolemia on a stable diet and maximally tolerated oral LDL-C lowering drug therapy

Secondary objectives 10

1. 1. To assess the LDL-C-lowering effects of lerodalcibep with LDL-C calculated by both Friedewald and Hopkins formulae compared to placebo at Weeks 12, 22, 24 and the mean of Weeks 22 and 24
2. 2. To assess the change in LDL-C, measured by preparative ultracentrifugation (PUC), from baseline (Week 0) with lerodalcibep compared to placebo at Week 12
3. 3. To assess safety and tolerability of lerodalcibep in pediatric patients with Heterozygous Familial Hypercholesterolemia
4. 4. To assess the pharmacodynamic (PD) effects of 300 mg lerodalcibep monthly on serum unbound (free) PCSK9 concentrations at Weeks 22 and 24
5. 5. To assess the effects of lerodalcibep on serum lipids, including total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), non-HDL-C, very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG)
6. 6. To assess the effects of lerodalcibep on ApoB and lipoprotein (a) (Lp[a]) serum concentrations compared to placebo at Weeks 12, 22, and 24, and the mean of Weeks 22 and 24
7. 7. To assess percentage of patients achieving current pediatric guidelines (EAS Consensus Panel 2015 target LDL-C < 3.5 mmol/L)
8. 8. To assess the effects on physical development and endocrine tests as appropriate for age and sex
9. 9. To assess the pharmacokinetics (PK) of lerodalcibep and total PCSK9 following 300 mg monthly subcutanous doses of lerodalcibep at Weeks 22 (peak post-dose) and 24 (trough post-dose)
10. 10. To assess the frequency and level of anti-drug antibodies (ADAs) (immunogenicity) following multiple subcutanous doses of lerodalcibep

Conditions and MedDRA coding

Heterozygous Familial Hypercholesterolemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002720-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Provision of written and signed informed consent/assent prior to any study-specific procedure
2. 2. Male or female, 6 to 17 years of age (defined as from 6 to less than 18 years of age), at the first Screening Visit
3. 3. Weight of more than 18 kg (40 lbs) and BMI more than 17 and less than 42 kg/m2
4. 4. Diagnosis of definite or probable Heterozygous Familial Hypercholesterolemia (HeFH) based on clinical criteria (SB Register, MEDPED or DLCN criteria) or genotyping and at the defined eligibility visit (Screening Visit or post washout/stabilization); a calculated LDL-C (Friedewald) equal or above 130 mg/dL and TG below 400 mg/dL while on stable lipid-lowering oral drug therapy (eg, maximally tolerated statin with or without ezetimibe); Note: Patients unable to tolerate approved doses of a statin may take lower than approved doses and less frequently than daily as long as the dose and dosing frequency is consistent per the Investigator's judgment. Patients with documented intolerance to statins may also participate.
5. 5. On a stable diet and lipid-lowering oral therapies (statins, ezetimibe, bile-acid sequestrants) or combinations thereof for at least 6 weeks (excluded oral lipid-lowering agents include mipomersen, lomitapide, and gemfibrozil)
6. 6. Patients on a PCSK9 mAb must undergo a washout period of ≥8 weeks after the last dose. For patients who have received an siRNA PCSK9 inhibitor the washout period is 360 days post last dose
7. 7. Females of childbearing potential must be using a highly effective form of contraception as specified in the study protocol during the study and until 60 days after last dose of study drug if sexually active and have negative urine pregnancy test during the trial and at the last Screening Visit
8. 8. Females of child bearing potential are not permitted to donate oocytes during exposure to the IMP or for 90 days after the last dose of study drug
9. 9. Male patients will either be surgically sterile or agree to use the following forms of contraception until 90 days after the last dose of study drug: male or female condom with spermicide and a female partner who is sterile or who agrees to use the following contraceptives: diaphragm or cervical cap with spermicide; or IUD, oral, implantable, or injectable contraceptives
10. 10. Male patients must refrain from sperm donation until 90 days following the last dose of study drug

Exclusion criteria 22

1. 1. Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months of screening or gemfibrozil within 6 weeks of the Screening Visit
2. 2. LDL or plasma apheresis within 2 months prior to Day 1
3. 3. Documented history of Homozygous Familial Hypercholesterolemia (HoFH) defined as clinical and/or genetic with true HoFH (ie, identical pathogenic variants), compound heterozygous (ie, 2 different pathogenic LDLR variants) or combined heterozygous (2 different pathogenic FH variants such as LDLR plus ApoB or LDLR plus PCSK9 gain-of function)
4. 4. History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator, including but not limited to clinically significant pulmonary, hematologic, gastrointestinal, endocrine (excluding diabetes), immunologic, dermatologic, neurologic, or psychiatric disease, which in the Investigator's opinion, would not be suitable for the study from a patient safety consideration or could interfere with the results of the study
5. 5. Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception as specified in the study protocol during the study and until 60 days after last dose of study drug, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit
6. 6. Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate <30 mL/min/1.73m2 at the Screening Visit
7. 7. Active liver disease or hepatic dysfunction (eg, cirrhosis, alcoholic liver disease, known hepatitis B or hepatitis C, autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, and/or AST or ALT >2.5 × the ULN based on age as determined by central laboratory analysis at screening (tests that result in ALT or AST up to 3 × ULN may have 1 repeat test to confirm eligibility during the Screening Period)
8. 8. Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) below the lower limit of normal (LLN) or >1.5 × ULN, respectively, at the Screening Visit. If TSH is above/below these cut-off points, the patient can enter if the free triiodothyronine (FT3) is within the reference range. If controlled, then treatment should be stable for at least 3 months prior to the Screening Visit
9. 9. Uncontrolled Type 1 or Type 2 diabetes mellitus (defined as fasting glucose above 200 mg/dL and HbA1c of above 9%)
10. 10. Uncontrolled serious cardiac arrhythmia (sustained ventricular tachycardia, frequent non sustained ventricular tachycardia, any ventricular fibrillation episode, wide-complex tachycardia, atrial fibrillation with rapid ventricular response, and severe second-degree or third degree atrioventricular block), myocardial infarction (MI), unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, placement of implantable cardioverter defibrillator or biventricular pacemaker, aortic valve surgery, or stroke within 3 months prior to enrollment (the day patient signs the informed consent/assent and first procedure is performed)
11. 11. Planned cardiac surgery or revascularization
12. 12. New York Heart Association III-IV heart failure; or patients with last documented left ventricular ejection fraction <30% by standard of care assessments (eg, echocardiography, cardiac magnetic resonance imaging, nuclear imaging, computed tomography angiography, or angiography with ventriculogram), within 12 months
13. 13. Uncontrolled hypertension defined as on treatment diastolic or systolic BP ≥95th percentile for age and sex
14. 14. Enrolled in another investigational device or drug study, or less than 30 days or 5 half-lives since ending another investigational device or drug study(ies), or receiving other investigational agent(s); such as PCSK9 or ANGPTL3 or Lp(a) siRNA or locked nucleic acid reducing agents within 12 months of the Screening Visit
15. 15. Unexplained CK >5 × ULN, unless related to exercise or unusual activity in which case 1 repeat test is allowed
16. 16. Patients who cannot be available for Protocol-required study visits or procedures, to the best of the patient's and Investigator's knowledge
17. 17. A history, within 6 months prior to screening, of prescription drug abuse, illicit drug use, or alcohol abuse according to medical history
18. 18. Donated or lost a significant volume (>500 mL) of blood or plasma within 30 days prior to Day 1
19. 19. Had a blood transfusion within 4 weeks of randomization or known diagnosis of human immunodeficiency virus
20. 20. Previous treatment with lerodalcibep or any adnectin product
21. 21. Have any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study
22. 22. An employee or family member of the Investigator or study site personnel

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percent change from baseline compared to placebo in LDL-C level (by preparative ultracentrifugation) at Week 24

Secondary endpoints 10

1. 1. Percent change in: o LDL-C level at Week 24 (by Hopkins formula and Friedewald); o LDL-C level at Weeks 12, 22 and the mean of Weeks 22 and 24 by Friedewald and Hopkins formula and LDL-C level at Week 24 by preparative ultracentrifugation
2. 2. Absolute and percent change (where not assessed prior) from baseline in LDL-C level by Friedewald and Hopkins formulas at all visits (Weeks 4, 8, 12, 16, 20, 22, and 24)
3. 3. Serum unbound (free) PCSK9 and PK concentrations in lerodalcibep patients at Day 1, Week 12, and Weeks 22 and 24. Other visits including Weeks 4, 8, 12, 16, and 20 will be measured in response to ADAs in lerodalcibep patients. Samples from placebo patients will be stored
4. 4. Percentage of patients achieving current pediatric guidelines (EAS Consensus Panel 2015 target LDL-C < 3.5 mmol/L)
5. 5. Growth and development including changes in height, weight, BMI, Tanner staging, and serum hormone levels (eg, estradiol, testosterone, dehydroepiandrosterone, follicle-stimulating hormone [FSH], luteinizing hormone, adrenocorticotropic hormone, and cortisol)
6. 6. Absolute and percent change from baseline in TC, HDL-C, non–HDL-C, VLDL-C, and TG at all visits (Weeks 4, 8, 12, 16, 20, 22, and 24)
7. 7. Absolute and percent change from baseline in ApoB and Lp(a) serum concentrations to Weeks 12, 22 and 24
8. 8. ADAs will be measured at Day 1 and Weeks 12 and 24/Early Termination (ET) in lerodalcibep patients. Measurements at other visits, including Weeks 4, 8, 16, and 20, may occur if ADAs are detected at Week 24/ET in lerodalcibep patients.
9. 9. The PK concentration for lerodalcibep and total serum PCSK9 will be measured at Weeks 12, 22 and Week 24/ET in lerodalcibep patients. Total serum PCSK9 will also be measured at Day 1. Other visits including Weeks 4, 8, 16, and 20 may be measured to support the population PK plan or the presence of ADAs in lerodalcibep patients.
10. 10. Safety endpoints are AEs, including the frequency of AEs, SAEs, SARs and AEs leading to treatment discontinuation, cardiovascular events and all-cause mortality; safety laboratory parameters (chemistry, hematology, coagulation, and urinalysis), with particular attention to hepatic (eg alanine transaminase/aspartate transaminase, total bilirubin, alkaline phosphatase), fasting glucose and HbA1c and skeletal muscle (ie creatine kinase) toxicities; 12-lead ECGs; ISRs; phys exam and vital signs

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

LIB Therapeutics Inc.

Sponsor organisation

LIB Therapeutics Inc.

Address

5375 Medpace Way

City

Cincinnati

Postcode

45227-1543

Country

United States

Scientific contact point

Organisation

LIB Therapeutics Inc.

Contact name

Evan Stein

Public contact point

Organisation

LIB Therapeutics Inc.

Contact name

Evan Stein

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 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