Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

A Three-Part, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

The primary objective for Part A of the study is to assess the pharmacokinetics (PK) of evinacumab in pediatric patients with homozygous familial hypercholesterolemia (HoFH).

The primary objective for Part B of the study is to demonstrate a reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab in pediatric (5 to 11 years of age) patients with HoFH.

The secondary objective for Part A of the study is to evaluate the safety and tolerability of evinacumab administered intravenous (IV) in pediatric patients with HoFH.

The secondary objectives for Part B of the study are:

• To evaluate the effect of evinacumab on other lipid parameters (ie, apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein a [Lp(a)]) in pediatric patients with HoFH
• To evaluate the safety and tolerability of evinacumab administered IV in pediatric patients with HoFH
• To assess the PK of evinacumab in pediatric patients with HoFH
• To assess the immunogenicity of evinacumab in pediatric patients with HoFH over time
• To evaluate patient efficacy by mutation status

Part A is Phase 1b Part B is Phase 3

Key Inclusion Criteria:

1. Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol
2. LDL-C >130 mg/dL at the screening visit
3. Body weight ≥15 kg
4. Receiving stable maximally tolerated therapy*at the screening visit *Maximally tolerated therapy could include a daily statin.
5. Willing and able to comply with clinic visits and study-related procedures
6. Parent(s) or legal guardian(s) must provide the signed informed consent form (ICF). Patients ≥5 years of age (or above age determined by the IRB/EC and in accordance with the local regulations and requirements) must also provide informed assent forms (IAFs) to enroll in the study, and sign and date a separate IAF or ICF signed by the parent(s)/legal guardian(s) (as appropriate based on local regulations and requirements)

Key Exclusion Criteria:

1. Background pharmacologic LMT, nutraceuticals or over-the-counter (OTC) therapies known to affect lipids, at a dose/regimen that has not been stable for at least 4 weeks (8 weeks for PCSK9 inhibitors) before the screening visit and patient is unwilling to enter the run-in period
2. For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit
3. Receiving lipid apheresis, a setting (if applicable) and schedule that has not been stable for approximately 8 weeks before the screening visit or an apheresis schedule that is not anticipated to be stable over the duration of the treatment period (48 weeks).
4. Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B
5. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
6. Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled diabetes as defined in the protocol

Note: Other protocol-defined criteria apply