Phase 3b Study of Lerodalcibep in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
- Trial ID
- 2025-524214-28-00
- Protocol
- LIB003-008
- Sponsor
- LIB Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the LDL-C reduction at Week 24 with monthly lerodalcibep 300 mg compared with placebo in children and adolescents aged 6 to 17 years with heterozygous familial hypercholesterolemia receiving a stable diet and maximally tolerated oral lipid-lowering therapy. This endpoint is clinically relevant because it assesses the degree of low-density lipoprotein cholesterol lowering achieved on top of background treatment. Secondary objectives include assessment of LDL-C lowering at Weeks 12, 22, 24, and the mean of Weeks 22 and 24 using Friedewald and Hopkins calculations; change in LDL-C measured by preparative ultracentrifugation at Week 12; safety and tolerability; pharmacodynamic effects on serum unbound PCSK9 at Weeks 22 and 24; effects on serum lipids including total cholesterol, HDL-C, non-HDL-C, VLDL-C, and triglycerides; effects on ApoB and lipoprotein(a) at Weeks 12, 22, and 24; proportion achieving the pediatric LDL-C target of <3.5 mmol/L; effects on physical development and endocrine tests as appropriate for age and sex; pharmacokinetics of lerodalcibep and total PCSK9 at Weeks 22 and 24; and frequency and level of anti-drug antibodies.
Participants
The trial included 145 participants with Heterozygous Familial Hypercholesterolemia. The study population consisted of male and female pediatric patients 6 to 17 years of age, with a weight greater than 18 kg and a BMI greater than 17 and less than 42 kg/m2. Participants were required to have a diagnosis of definite or probable Heterozygous Familial Hypercholesterolemia or a genotypic confirmation, and to have an LDL-C level of at least 130 mg/dL with triglycerides below 400 mg/dL while receiving stable lipid-lowering oral therapy. Selection was based on written informed consent or assent and on eligibility assessment at screening. The population was maintained on a stable diet and lipid-lowering oral therapies for at least 6 weeks before enrollment. Relevant criteria included prior washout from PCSK9-targeted therapies and the use of appropriate contraception requirements for sexually active participants of childbearing potential and male participants.
Plans and Procedures
The study is a randomized, placebo-controlled, double-blind, phase 3b trial evaluating monthly subcutaneous lerodalcibep 300 mg versus matching placebo in children and adolescents 6 to 17 years of age with heterozygous familial hypercholesterolemia on a stable diet and maximally tolerated oral lipid-lowering therapy. The treatment period lasts 24 weeks, and the overall trial duration extends from the planned start in 2026 to the planned end in 2027. The sequence of study procedures includes a screening visit to confirm eligibility, obtain informed consent or assent, and assess baseline clinical and laboratory criteria, followed by scheduled follow-up visits during treatment at Weeks 4, 8, 12, 16, 20, 22, and 24 to evaluate efficacy, pharmacokinetics, immunogenicity, growth and development, and safety. An end-of-study visit occurs at Week 24 or at early termination to complete final assessments. Participant involvement is expected to last up to 24 weeks, with possible early termination in cases of treatment discontinuation, withdrawal, loss to follow-up, or other protocol-defined reasons requiring study discontinuation.
Treatment
Lerodalcibep was administered as a solution for injection in a pre-filled pen at a dose of 300 mg by subcutaneous injection monthly. The study evaluated monthly dosing in pediatric participants 6 to 17 years of age with heterozygous familial hypercholesterolemia on stable diet and maximally tolerated oral LDL-C lowering therapy.
A placebo matching lerodalcibep, solution for injection in pre-filled pen/injector, was used as the comparator treatment. The study was randomized, placebo-controlled, and double-blind. LDL-C reduction was assessed at Week 24.
Efficacy
Efficacy will be assessed by the percent change from baseline in LDL-C compared with placebo at Week 24, using preparative ultracentrifugation. Additional efficacy assessments include percent change in LDL-C at Week 24 by Hopkins formula and Friedewald, and at Weeks 12, 22, and the mean of Weeks 22 and 24 by Friedewald and Hopkins formula. Absolute and percent change from baseline in LDL-C by Friedewald and Hopkins formulas will also be evaluated at all visits at Weeks 4, 8, 12, 16, 20, 22, and 24.
Further efficacy parameters include the percentage of patients achieving the current pediatric guideline target LDL-C of less than 3.5 mmol/L, absolute and percent change from baseline in total cholesterol, HDL-C, non-HDL-C, VLDL-C, and triglycerides at all visits at Weeks 4, 8, 12, 16, 20, 22, and 24, and absolute and percent change from baseline in ApoB and Lp(a) serum concentrations at Weeks 12, 22, and 24. Serum unbound free PCSK9 and pharmacokinetic concentrations will be measured in lerodalcibep patients at Day 1, Week 12, and Weeks 22 and 24, with additional measurements at Weeks 4, 8, 12, 16, and 20 in response to ADAs. Total serum PCSK9 will be measured at Day 1 and at Weeks 12, 22, and 24/Early Termination, with additional measurements at Weeks 4, 8, 16, and 20 as needed to support the population PK plan or the presence of ADAs.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Provision of written and signed informed consent/assent prior to any study-specific procedure
- 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
- Weight of more than 18 kg (40 lbs) and BMI more than 17 and less than 42 kg/m2
- 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.
- 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)
- 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
- 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
- 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
- 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
- Male patients must refrain from sperm donation until 90 days following the last dose of study drug
Exclusion Criteria
- Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months of screening or gemfibrozil within 6 weeks of the Screening Visit
- LDL or plasma apheresis within 2 months prior to Day 1
- 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)
- 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
- 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
- Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate <30 mL/min/1.73m2 at the Screening Visit
- 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)
- 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
- Uncontrolled Type 1 or Type 2 diabetes mellitus (defined as fasting glucose above 200 mg/dL and HbA1c of above 9%)
- 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)
- Planned cardiac surgery or revascularization
- 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
- Uncontrolled hypertension defined as on treatment diastolic or systolic BP ≥95th percentile for age and sex
- 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
- Unexplained CK >5 × ULN, unless related to exercise or unusual activity in which case 1 repeat test is allowed
- Patients who cannot be available for Protocol-required study visits or procedures, to the best of the patient's and Investigator's knowledge
- A history, within 6 months prior to screening, of prescription drug abuse, illicit drug use, or alcohol abuse according to medical history
- Donated or lost a significant volume (>500 mL) of blood or plasma within 30 days prior to Day 1
- Had a blood transfusion within 4 weeks of randomization or known diagnosis of human immunodeficiency virus
- Previous treatment with lerodalcibep or any adnectin product
- Have any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study
- An employee or family member of the Investigator or study site personnel
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Norway | Recruiting | 27 Jul 2026 | 5 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Lerodalcibep | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS USE | 300 | 24 | PRD13416982 |
Placebo matching lerodalcibep, solution for injection in pre-filled pen/injector | Placebo | N/A | — | — | — | N/A |