Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

NCT03399786 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: R1500-CL-16292017-001388-19
• Study Type: interventional
• Target: 65
• Locations: 10 countries
• Sites: 28

Brief Summary

The primary objective of the study is to demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab intravenously (IV) in comparison to placebo after 24 weeks in patients with homozygous familial hypercholesterolemia (HoFH). The secondary objectives of the study are to evaluate the effect of evinacumab IV on other lipid parameters, evaluate the effect of evinacumab on LDL-C goal attainment, assess the effect of evinacumab on eligibility for apheresis (using German and US apheresis criteria), evaluate the safety and tolerability of evinacumab in patients with HoFH, assess the pharmacokinetics (PK) of evinacumab in patients with HoFH and evaluate the potential development of anti-evinacumab antibodies.

Conditions

Homozygous Familial Hypercholesterolemia

Keywords

HoFH

Outcome Measures

Primary Outcomes (1)

• Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand)

  Percent change was calculated as 100x(calculated LDL-C value at Week 24 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. The baseline LDL-C value was the last calculated LDL-C value obtained before the first dose of double-blind-study drug. The calculated LDL-C at week 24 was the LDL-C value obtained within the week 24 efficacy analysis window, regardless of adherence to treatment and subsequent therapies (intent-to-treat \[ITT\] estimand). The ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

  Week 24

Secondary Outcomes (16)

• Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)

  Week 24

• Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)

  Week 24

• Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)

  Week 24

• Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)

  At Week 24

• Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)

  At Week 24

Study Arms (2)

evinacumab

EXPERIMENTAL

Drug: evinacumab

Placebo

EXPERIMENTAL

Drug: Placebo

Interventions

evinacumab DRUG

IV administration of evinacumab

Also known as: REGN1500

evinacumab

Placebo DRUG

IV administration of placebo

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of functional HoFH
• If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly or every other week schedule and/or stable settings for at least 8 weeks
• Willing to consistently maintain his/her usual low fat or heart-healthy diet for the duration of the study

You may not qualify if:

• LDL-C level \<70 mg/dL (1.81 mmol/L) at the screening visit
• Background medical Lipid Modifying Therapy (LMT) (if applicable) that has not been stable before the screening visit
• Lipid-apheresis schedule /apheresis settings (if applicable) that have not been stable for at least 8 weeks before the screening visit
• Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit
• 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 (HbA1c \>9%) diabetes
• History of a MI, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit
• Pregnant or breastfeeding women
• Sexually active women of child bearing potential (WOCBP), who are unwilling to practice a highly effective birth control method prior to the initial dose, during the study, and for 24 weeks after the last dose of study drug
• Men who are sexually active with women of child bearing potential (WOCBP) and are unwilling to consistently use condoms during the study drug treatment period and for 24 weeks after the last dose of study drug regardless of vasectomy status

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (30)

Regeneron Research Site

Boca Raton, Florida, 33434, United States

Location

Regeneron Research Site

Boston, Massachusetts, 02114, United States

Location

Regeneron Research Site

New York, New York, 10029, United States

Location

Regeneron Research Site

Cincinnati, Ohio, 45227, United States

Location

Regeneron Research Site

Portland, Oregon, 97239, United States

Location

Regeneron Research Site

Dallas, Texas, 78226, United States

Location

Regeneron Research Site

Camperdown, New South Wales, 2050, Australia

Location

Regeneron Research Site

Perth, Western Australia, 6000, Australia

Location

Regeneron Research Site

Innsbruck, 6020, Austria

Location

Regeneron Research Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Regeneron Research Site

Québec, Quebec, G1V 4W2, Canada

Location

Regeneron Research Site

Paris, Cedex, 75651, France

Location

Regeneron Research Site

Marseille, 13385, France

Location

Regeneron Research Site

Ioannina, Ioannina, 45500, Greece

Location

Regeneron Research Site

Athens, 17674, Greece

Location

Regeneron Research Site # 2

Napoli, 80131, Italy

Location

Regeneron Research Site

Kurume, Fukuoka, 830-8522, Japan

Location

Regeneron Research Site

Nishinomiya, Hyōgo, 662-0918, Japan

Location

Regeneron Research Site

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Regeneron Research Site #3

Suita, Osaka, 565-0871, Japan

Location

Regeneron Research Site

Suita, Osaka, 565-8565, Japan

Location

Regeneron Research Site

Osaka, 530-0001, Japan

Location

Regeneron Research Site

Amsterdam, 1105 AZ, Netherlands

Location

Regeneron Research Site

Rotterdam, 3045 PM, Netherlands

Location

Regeneron Research Site

Parktown, Johannesburg, 2000, South Africa

Location

Regeneron Research Site

Ivano-Frankivsk, 76075, Ukraine

Location

Regeneron Research Site

Kharkiv, 61039, Ukraine

Location

Regeneron Research Site #2

Kharkiv, 61176, Ukraine

Location

Regeneron Research Site #2

Kyiv, 02660, Ukraine

Location

Regeneron Research Site

Kyiv, 03680, Ukraine

Location

Related Publications (2)

• Iannuzzo G, Calcaterra I, Gentile M, Stanzione C, De Ruberto F, Di Taranto MD, Fortunato G, Di Minno M. Evinacumab for Homozygous Familial Hypercholesterolemia: The Italian Cohort of the ELIPSE HoFH Study. Adv Ther. 2025 May;42(5):2465-2479. doi: 10.1007/s12325-025-03160-4. Epub 2025 Apr 2.

  PMID: 40169529 DERIVED

• Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, Ali S, Banerjee P, Chan KC, Gipe DA, Khilla N, Pordy R, Weinreich DM, Yancopoulos GD, Zhang Y, Gaudet D; ELIPSE HoFH Investigators. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Aug 20;383(8):711-720. doi: 10.1056/NEJMoa2004215.

  PMID: 32813947 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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 16, 2018
• Study Start: January 18, 2018
• Primary Completion: June 10, 2019
• Study Completion: March 17, 2020
• Last Updated: May 18, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-04

Locations

NL (2); UA (5); AU (1); ZA (1); GR (2); JP (6); US (6); FR (2); CA (2); IT (1)