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Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Primary Purpose

Homozygous Familial Hypercholesterolemia

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

evinacumab

Placebo

About this trial

This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia focused on measuring HoFH

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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

Key Exclusion Criteria:

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

Note: Other protocol defined inclusion/exclusion criteria may apply.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

evinacumab

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Percent change in Apo B from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Percent change from baseline in non-HDL-C at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Percent change in TC from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Percentage of participants who achieved reduction in calculated LDL-C ≥30% at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Percentage of participants who achieved reduction in calculated LDL-C ≥ 50% at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand)

Absolute change in calculated LDL-C from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)

US apheresis eligibility criteria included participants who had inadequate response to diet and LMTs after 6 months of treatment and with functional Homozygous familial hypercholesterolemia (HoFH) or Heterozygous familial hypercholesterolemia (HeFH) (with 0-1 risk factor) with LDL-C ≥ 300 mg/dL (7.77 mmol/L). Percentage of participants who met US apheresis eligibility criteria at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

Percentage of Participants With Low-Density Lipoprotein Cholesterol (LDL-C) <100 Milligrams Per Deciliter (mg/dL) (2.59 Millimoles Per Liter [mmol/L]) at Week 24 (ITT Estimand)

Percentage of participants with LDL-C value <100 mg/dL (2.59 mmol/L) in the DBTP at Week 24 was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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 analysed according to the treatment group allocated by randomization (i.e., as randomized participant group).

Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)

EU apheresis eligibility criteria included participants who had inadequate response to diet and Lipid modifying therapies (LMTs) after 3 months of treatment, Primary prevention: Participants with Familial hypercholesterolemia (FH) with LDL-C >160 mg/dL (4.2 mmol/L) and Cardiovascular (CV) events in close relatives. Secondary prevention: Participants with progressive CV events with LDL-C > 120 to 130 mg/dL (3.1-3.4 mmol/L). Percentage of participants who met EU apheresis eligibility criteria at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand)

Percentage of participants with LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand)

Percent change from baseline in TG at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand)

Percent change in Lp(a) from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Absolute change in Apo B from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Absolute change in non-HDL-C from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Absolute change in TC from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

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

Percent change in Apo CIII from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). 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).

Full Information

NCT ID

NCT03399786

First Posted

January 8, 2018

Last Updated

April 26, 2021

Sponsor

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03399786

Brief Title

Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Official Title

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

January 18, 2018 (Actual)

Primary Completion Date

June 10, 2019 (Actual)

Study Completion Date

March 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Homozygous Familial Hypercholesterolemia

Keywords

HoFH

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

evinacumab

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

evinacumab

Other Intervention Name(s)

REGN1500

Intervention Description

IV administration of evinacumab

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

IV administration of placebo

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Week 24

Title

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

Description

Time Frame

At Week 24

Title

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

Description

Time Frame

At Week 24

Title

Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand)

Description

Time Frame

Week 24

Title

Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)

Description

Time Frame

At Week 24

Title

Percentage of Participants With Low-Density Lipoprotein Cholesterol (LDL-C) <100 Milligrams Per Deciliter (mg/dL) (2.59 Millimoles Per Liter [mmol/L]) at Week 24 (ITT Estimand)

Description

Time Frame

At Week 24

Title

Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)

Description

Time Frame

At Week 24

Title

Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand)

Description

Time Frame

At Week 24

Title

Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand)

Description

Time Frame

Week 24

Title

Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand)

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Week 24

Title

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

Description

Time Frame

Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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 Key Exclusion Criteria: 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 Note: Other protocol defined inclusion/exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Management

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Regeneron Research Site

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33434

Country

United States

Facility Name

Regeneron Research Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Regeneron Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Regeneron Research Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45227

Country

United States

Facility Name

Regeneron Research Site

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Regeneron Research Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

78226

Country

United States

Facility Name

Regeneron Research Site

City

Camperdown

State/Province

New South Wales

ZIP/Postal Code

2050

Country

Australia

Facility Name

Regeneron Research Site

City

Perth

State/Province

Western Australia

ZIP/Postal Code

6000

Country

Australia

Facility Name

Regeneron Research Site

City

Innsbruck

ZIP/Postal Code

6020

Country

Austria

Facility Name

Regeneron Research Site

City

Chicoutimi

State/Province

Quebec

ZIP/Postal Code

G7H 7K9

Country

Canada

Facility Name

Regeneron Research Site

City

Québec

State/Province

Quebec

ZIP/Postal Code

G1V 4W2

Country

Canada

Facility Name

Regeneron Research Site

City

Paris

State/Province

Cedex

ZIP/Postal Code

75651

Country

France

Facility Name

Regeneron Research Site

City

Marseille

ZIP/Postal Code

13385

Country

France

Facility Name

Regeneron Research Site

City

Ioánnina

State/Province

Ioannina

ZIP/Postal Code

45500

Country

Greece

Facility Name

Regeneron Research Site

City

Athens

ZIP/Postal Code

17674

Country

Greece

Facility Name

Regeneron Research Site # 2

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Facility Name

Regeneron Research Site

City

Kurume

State/Province

Fukuoka

ZIP/Postal Code

830-8522

Country

Japan

Facility Name

Regeneron Research Site

City

Nishinomiya

State/Province

Hyogo

ZIP/Postal Code

662-0918

Country

Japan

Facility Name

Regeneron Research Site

City

Kanazawa

State/Province

Ishikawa

ZIP/Postal Code

920-8641

Country

Japan

Facility Name

Regeneron Research Site #3

City

Suita

State/Province

Osaka

ZIP/Postal Code

565-0871

Country

Japan

Facility Name

Regeneron Research Site

City

Suita

State/Province

Osaka

ZIP/Postal Code

565-8565

Country

Japan

Facility Name

Regeneron Research Site

City

Osaka

ZIP/Postal Code

530-0001

Country

Japan

Facility Name

Regeneron Research Site

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Regeneron Research Site

City

Rotterdam

ZIP/Postal Code

3045 PM

Country

Netherlands

Facility Name

Regeneron Research Site

City

Parktown

State/Province

Johannesburg

ZIP/Postal Code

2000

Country

South Africa

Facility Name

Regeneron Research Site

City

Ivano-Frankivs'k

ZIP/Postal Code

76075

Country

Ukraine

Facility Name

Regeneron Research Site

City

Kharkiv

ZIP/Postal Code

61039

Country

Ukraine

Facility Name

Regeneron Research Site #2

City

Kharkiv

ZIP/Postal Code

61176

Country

Ukraine

Facility Name

Regeneron Research Site #2

City

Kyiv

ZIP/Postal Code

02660

Country

Ukraine

Facility Name

Regeneron Research Site

City

Kyiv

ZIP/Postal Code

03680

Country

Ukraine

12. IPD Sharing Statement

Citations:

PubMed Identifier

32813947

Citation

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.

Results Reference

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Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

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Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Homozygous Familial Hypercholesterolemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial