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

NCT04233918 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: R1500-CL-171002019-001931-30
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 10

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

Conditions

Homozygous Familial Hypercholesterolemia

Keywords

HoFH

Outcome Measures

Primary Outcomes (4)

• Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab

  Cmax was obtained directly from the plasma concentration versus time curve.

  At day 12

• Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab

  AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.

  Up to Week 12

• Part A: Terminal Half-Life (t1/2) of Evinacumab

  T1/2 was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.

  Up to week 12

• Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24

  Percent change was calculated as 100 multiplied by (calculated LDL-C value at Week 24 minus calculated LDL-C value at baseline) divided by calculated LDL-C value at baseline.

  Baseline to Week 24

Secondary Outcomes (13)

• Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Part A: up to Week 24; Part B: up to Week 48

• Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24

  Baseline to Week 24

• Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24

  Baseline to Week 24

• Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24

  Baseline to Week 24

• Part B: Percentage of Participants With ≥50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24

  Week 24

Study Arms (1)

Evinacumab

EXPERIMENTAL

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

Drug: Evinacumab

Interventions

Evinacumab DRUG

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

Also known as: REGN1500, Evkeeza™

Evinacumab

Eligibility Criteria

• Age: 5 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (11)

Regeneron Research Site

Wilmington, Delaware, 19803, United States

Location

Regeneron Research Site

Boca Raton, Florida, 33434, United States

Location

Regeneron Research Site

Kansas City, Kansas, 66190, United States

Location

Regeneron Research Center

Boston, Massachusetts, 02115, United States

Location

Regeneron Research Center

Philadelphia, Pennsylvania, 19106, United States

Location

Regeneron Research Center

Salt Lake City, Utah, 84108, United States

Location

Regeneron Research Center

Westmead, New South Wales, 2145, Australia

Location

Regeneron Research Site

Vienna, 1090, Austria

Location

Regeneron Research Site

Amsterdam, 1105 AZ, Netherlands

Location

Regeneron Research Center

Taipei, 11217, Taiwan

Location

Regeneron Research Site

Kyiv, 04209, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 37860863 DERIVED

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

evinacumab

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 18, 2020
• Study Start: June 29, 2020
• Primary Completion: January 31, 2022
• Study Completion: May 30, 2023
• Last Updated: July 16, 2024
• Results First Posted: June 7, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency \[EMA\], Pharmaceuticals and Medical Devices Agency \[PMDA\], etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).

Locations

UA (1); US (6); AU (1); NL (1); TW (1)