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

NCT ID: NCT04233918

Last Updated: 2024-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-29
• Study Completion Date: 2023-05-30

Brief 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

Detailed Description

Part A is Phase 1b Part B is Phase 3

Conditions

Homozygous Familial Hypercholesterolemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Evinacumab

Part A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 20 Part C: IV dose Q4W

Group Type: EXPERIMENTAL

Evinacumab

Intervention Type: DRUG

Part A: Single IV dose Part B \& C: IV dose Q4W

Interventions

Evinacumab

Part A: Single IV dose Part B \& C: IV dose Q4W

Intervention Type: DRUG

Other Intervention Names

REGN1500; Evkeeza™

Eligibility Criteria

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)

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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

Regeneron Research Site

Wilmington, Delaware, United States

Regeneron Research Site

Boca Raton, Florida, United States

Regeneron Research Site

Kansas City, Kansas, United States

Regeneron Research Center

Boston, Massachusetts, United States

Regeneron Research Center

Philadelphia, Pennsylvania, United States

Regeneron Research Center

Salt Lake City, Utah, United States

Regeneron Research Center

Westmead, New South Wales, Australia

Regeneron Research Site

Vienna, , Austria

Regeneron Research Site

Amsterdam, , Netherlands

Regeneron Research Center

Taipei, , Taiwan

Regeneron Research Site

Kyiv, , Ukraine

Countries

United States; Australia; Austria; Netherlands; Taiwan; Ukraine

References

Wiegman A, Greber-Platzer S, Ali S, Reijman MD, Brinton EA, Charng MJ, Srinivasan S, Baker-Smith C, Baum S, Brothers JA, Hartz J, Moriarty PM, Mendell J, Bihorel S, Banerjee P, George RT, Hirshberg B, Pordy R. Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia. Circulation. 2024 Jan 30;149(5):343-353. doi: 10.1161/CIRCULATIONAHA.123.065529. Epub 2023 Oct 20.

Reference Type: DERIVED

PMID: 37860863 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-001931-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R1500-CL-17100

Identifier Type: -

Identifier Source: org_study_id