Phase 3 N=20 Treatment

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

Homozygous Familial Hypercholesterolemia

Bottom Line

View on ClinicalTrials.gov: NCT04233918 ↗

Enrolled (actual)

Serious AEs

5.0%

Results posted

Jun 2023

Primary outcome: Primary: Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab — 238 Milligrams per Liter (mg/L)

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Evinacumab (Drug)
Age: Pediatric · 5+ yrs
Sex: All
Sponsor: Regeneron Pharmaceuticals
Primary completion: Jan 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab	238	—
PRIMARY Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab	4576	—
PRIMARY Part A: Terminal Half-Life (t1/2) of Evinacumab	7.69	—
PRIMARY Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24	-48.3	—
SECONDARY Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	5; 10	—
SECONDARY Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24	-41.3	—
SECONDARY Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24	-48.9	—
SECONDARY Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24	-49.1	—
SECONDARY Part B: Percentage of Participants With ≥50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24	78.6	—
SECONDARY Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants Who Have Negative/Negative and Null/Null Mutations	-67.7; -57.2	—
SECONDARY Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24	-37.3	—
SECONDARY Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24	-131.9	—
SECONDARY Part B: Serum Concentration of Total Evinacumab	0; 256; 62.6; 293; 98.8; 356	—
SECONDARY Part B: Maximum Serum Concentration at Steady State (Cmax,ss) of Evinacumab	428.9	—
SECONDARY Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab	7019	—
SECONDARY Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) of Evinacumab	171.8	—
SECONDARY Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants Who Have by Null/Null vs. Non-null/Null and Negative/Negative vs.Non-negative/Negative Mutations	-67.7; -43.0; -57.2; -47.6	—

Summary

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

Eligibility Criteria

Key Inclusion Criteria

Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol
LDL-C >130 mg/dL at the screening visit
Body weight ≥15 kg
Receiving stable maximally tolerated therapy*at the screening visit *Maximally tolerated therapy could include a daily statin.
Willing and able to comply with clinic visits and study-related procedures
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

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
For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit
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).
Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B
Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04233918). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.