Heterozygous Familial Hypercholesterolemia HeFH
Conditions
Interventions
Placebo
Sponsors
Sponsor LIB Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provision of written and signed informed consent/assent prior to any study-specific procedure. 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.Weight of more than 18 kg (40 lbs) and BMI more than 17 and less than42 kg/m2. 4.Diagnosis of definite, probable, or possible HeFH based on clinical criteria; a calculated LDL-C (Friedewald) equal or above 130 mg/dL or, if the patient has additional risk factors as defined. 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.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.Females of childbearing potential must be using a highly effective form of contraception if sexually active and have negative urine pregnancy test at the last Screening Visit. 8.Male patients will either be surgically sterile or agree to use the specified forms of contraception: male or female condom with spermicide and a female partner who is sterile or who agrees to use the specified contraceptives. 9.Male patients must refrain from sperm donation until 90 days following the last dose of study medication.
Exclusion criteria
Exclusion criteria: 1.Use of prohibited oral lipid-lowering agents mipomersen or lomitapide within 6 months of screening/gemfibrozil within 6 weeks of Screening. 2.LDL/plasma apheresis within 2 months prior to Day 1. 3.Documented history of HoFH as defined. 4.History of any prior/active clinical condition or acute and/or unstable systemic disease. 5.Females of childbearing potential: sexually active/not using or unwilling to use a highly effective form of contraception/pregnant/breastfeeding, or who have a positive urine pregnancy test at Screening. 6.Moderate to severe renal dysfunction: eGFR 2.5 × the ULN based on age. 8.Uncontrolled thyroid disease: hyperthyroidism/hypothyroidism as defined. 9.Uncontrolled Type 1/Type 2 diabetes mellitus (fasting glucose above 200 mg/dL and HbA1c above 9%). 10.Uncontrolled serious cardiac arrhythmia,myocardial infarction,unstable angina,percutaneous coronary intervention,coronary artery bypass grafting,placement of implantable cardioverter defibrillator/biventricular pacemaker,aortic valve surgery,stroke within 3 months prior to enrollment. 11.Planned cardiac surgery/revascularization. 12.New York Heart Association III-IV heart failure/patients with last documented left ventricular ejection fraction 5 ×ULN, unless related to exercise/other unusual activity. 16.A history, within 6 months prior to screening: prescription medication abuse/illicit drug use/alcohol abuse. 17.Donated/lost >500 mL blood/plasma within 30 days prior to Day 1. 18.Had a blood transfusion within 4 weeks of randomization/known diagnosis of HIV. 19.Previous treatment with lerodalcibep/adnectin products.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The co-primary objectives of this study are to assess the LDL-C reductions at Week 12 and Week 24 with monthly dosing of lerodalcibep 300 mg compared to placebo, in pediatric patients 6 to 17 years of age, with HeFH on a stable diet and maximally tolerated oral LDL C lowering drug therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the LDL-C-lowering effects of lerodalcibep with LDL-C calculated by Friedewald formula compared to placebo at Week 22 and the mean of Weeks 22 and 24; To assess the change in LDL-C, measured by preparative ultracentrifugation (PUC), from baseline (Week 0) with lerodalcibep compared to placebo at Week 24; To assess safety and tolerability of lerodalcibep in pediatric patients with HeFH; To assess the pharmacodynamic (PD) effects of 300 mg lerodalcibep QM on serum unbound (free) PCSK9 concentrations at Weeks 22 and 24; 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); 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; To assess the pharmacokinetics (PK) of lerodalcibep and total PCSK9 following 300 mg QM SC doses of lerodalcibep at Weeks 22 (peak post-dose) and 24 (trough post-dose); and To assess the frequency and level of anti-drug antibodies (ADAs) (immunogenicity) following multiple SC doses of lerodalcibep. | — |
Countries
South Africa
Contacts
Public ContactCarolyn Glashagen
CRO
Outcome results
None listed