Randomized, Placebo-Controlled, Double-Blind, Phase 3b Study to Evaluate the Efficacy and Safety of Lerodalcibep in Children 6 to 17 Years, With Heterozygous FH

Exclusion Criteria

• •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. LDL or plasma apheresis within 2 months prior to Day 1;
• •3. Documented history of 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. 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. Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit; Note: Highly effective methods of birth control include refraining from heterosexual sexual intercourse during the entire period of risk, birth control pills or patches, IUDs, sexual activity with a male partner who has had a vasectomy, condom or diaphragm or cervical cap with spermicide or IUD, oral, implantable, or injectable contraceptives.
• •6. Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate \<30 mL/min/1.73m2 at the Screening Visit;
• •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. 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. Uncontrolled Type 1 or Type 2 diabetes mellitus (defined as fasting glucose above 200 mg/dL and HbA1c of above 9%);
• •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. Planned cardiac surgery or revascularization;
• •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. Uncontrolled hypertension defined as a reproducible (ie, repeated 5 minutes apart) sitting blood pressure above 160 mmHg systolic or above 100 mmHg diastolic;
• •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. Unexplained CK \>5 × ULN, unless related to exercise or unusual activity in which case 1 repeat test is allowed;
• •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. A history, within 6 months prior to screening, of prescription drug abuse, illicit drug use, or alcohol abuse according to medical history;
• •18. Donated or lost a significant volume (\>500 mL) of blood or plasma within 30 days prior to Day 1;
• •19. Had a blood transfusion within 4 weeks of randomization or known diagnosis of human immunodeficiency virus;
• •20. Previous treatment with lerodalcibep or any adnectin product;
• •21. Have any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study; or
• •22. An employee or family member of the Investigator or study site personnel.