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Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

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ClinicalTrials.gov Identifier: NCT03399786
Recruitment Status : Completed
First Posted : January 16, 2018
Results First Posted : May 18, 2021
Last Update Posted : May 18, 2021
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Homozygous Familial Hypercholesterolemia Drug: evinacumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 18, 2018
Actual Primary Completion Date : June 10, 2019
Actual Study Completion Date : March 17, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Evinacumab

Arm Intervention/treatment
Experimental: evinacumab Drug: evinacumab
IV administration of evinacumab
Other Name: REGN1500

Experimental: Placebo Drug: Placebo
IV administration of placebo




Primary Outcome Measures :
  1. Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand) [ Time Frame: Week 24 ]
    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 :
  1. Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  2. Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  3. Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  4. Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand) [ Time Frame: At Week 24 ]
    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).

  5. Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand) [ Time Frame: At Week 24 ]
    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).

  6. Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  7. Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand) [ Time Frame: At Week 24 ]
    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).

  8. 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) [ Time Frame: At Week 24 ]
    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).

  9. Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand) [ Time Frame: At Week 24 ]
    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).

  10. Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand) [ Time Frame: At Week 24 ]
    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).

  11. Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  12. Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  13. Absolute Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  14. Absolute Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  15. Absolute Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).

  16. Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline to Week 24 (ITT Estimand) [ Time Frame: Week 24 ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Diagnosis of functional HoFH
  2. 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
  3. Willing to consistently maintain his/her usual low fat or heart-healthy diet for the duration of the study

Key Exclusion Criteria:

  1. LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit
  2. Background medical Lipid Modifying Therapy (LMT) (if applicable) that has not been stable before the screening visit
  3. Lipid-apheresis schedule /apheresis settings (if applicable) that have not been stable for at least 8 weeks before the screening visit
  4. 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
  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 (HbA1c >9%) diabetes
  7. 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
  8. Pregnant or breastfeeding women
  9. 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
  10. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03399786


Locations
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United States, Florida
Regeneron Research Site
Boca Raton, Florida, United States, 33434
United States, Massachusetts
Regeneron Research Site
Boston, Massachusetts, United States, 02114
United States, New York
Regeneron Research Site
New York, New York, United States, 10029
United States, Ohio
Regeneron Research Site
Cincinnati, Ohio, United States, 45227
United States, Oregon
Regeneron Research Site
Portland, Oregon, United States, 97239
United States, Texas
Regeneron Research Site
Dallas, Texas, United States, 78226
Australia, New South Wales
Regeneron Research Site
Camperdown, New South Wales, Australia, 2050
Australia, Western Australia
Regeneron Research Site
Perth, Western Australia, Australia, 6000
Austria
Regeneron Research Site
Innsbruck, Austria, 6020
Canada, Quebec
Regeneron Research Site
Chicoutimi, Quebec, Canada, G7H 7K9
Regeneron Research Site
Québec, Quebec, Canada, G1V 4W2
France
Regeneron Research Site
Paris, Cedex, France, 75651
Regeneron Research Site
Marseille, France, 13385
Greece
Regeneron Research Site
Ioánnina, Ioannina, Greece, 45500
Regeneron Research Site
Athens, Greece, 17674
Italy
Regeneron Research Site # 2
Napoli, Italy, 80131
Japan
Regeneron Research Site
Kurume, Fukuoka, Japan, 830-8522
Regeneron Research Site
Nishinomiya, Hyogo, Japan, 662-0918
Regeneron Research Site
Kanazawa, Ishikawa, Japan, 920-8641
Regeneron Research Site #3
Suita, Osaka, Japan, 565-0871
Regeneron Research Site
Suita, Osaka, Japan, 565-8565
Regeneron Research Site
Osaka, Japan, 530-0001
Netherlands
Regeneron Research Site
Amsterdam, Netherlands, 1105 AZ
Regeneron Research Site
Rotterdam, Netherlands, 3045 PM
South Africa
Regeneron Research Site
Parktown, Johannesburg, South Africa, 2000
Ukraine
Regeneron Research Site
Ivano-Frankivs'k, Ukraine, 76075
Regeneron Research Site
Kharkiv, Ukraine, 61039
Regeneron Research Site #2
Kharkiv, Ukraine, 61176
Regeneron Research Site #2
Kyiv, Ukraine, 02660
Regeneron Research Site
Kyiv, Ukraine, 03680
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:
Study Protocol  [PDF] October 11, 2019
Statistical Analysis Plan  [PDF] July 16, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03399786    
Other Study ID Numbers: R1500-CL-1629
2017-001388-19 ( EudraCT Number )
First Posted: January 16, 2018    Key Record Dates
Results First Posted: May 18, 2021
Last Update Posted: May 18, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
HoFH
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias