Clinical trial NCT03399786: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: HoFH
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-01-16
Enrollment: 65
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand)
timeFrame: Week 24
Secondary outcomes:
measure: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
timeFrame: At Week 24
measure: Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
timeFrame: At Week 24
measure: Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
timeFrame: At Week 24
measure: 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)
timeFrame: At Week 24
measure: Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
timeFrame: At Week 24
measure: Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand)
timeFrame: At Week 24
measure: Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Absolute Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Absolute Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Absolute Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
measure: Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline to Week 24 (ITT Estimand)
timeFrame: Week 24
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Regeneron Research Site
state: Florida
city: Boston
country: United States
facility: Regeneron Research Site
state: Massachusetts
city: New York
country: United States
facility: Regeneron Research Site
state: New York
city: Cincinnati
country: United States
facility: Regeneron Research Site
state: Ohio
city: Portland
country: United States
facility: Regeneron Research Site
state: Oregon
city: Dallas
country: United States
facility: Regeneron Research Site
state: Texas
city: Camperdown
country: Australia
facility: Regeneron Research Site
state: New South Wales
city: Perth
country: Australia
facility: Regeneron Research Site
state: Western Australia
city: Innsbruck
country: Austria
facility: Regeneron Research Site
city: Chicoutimi
country: Canada
facility: Regeneron Research Site
state: Quebec
city: Québec
country: Canada
facility: Regeneron Research Site
state: Quebec
city: Paris
country: France
facility: Regeneron Research Site
state: Cedex
city: Marseille
country: France
facility: Regeneron Research Site
city: Ioánnina
country: Greece
facility: Regeneron Research Site
state: Ioannina
city: Athens
country: Greece
facility: Regeneron Research Site
city: Napoli
country: Italy
facility: Regeneron Research Site # 2
city: Kurume
country: Japan
facility: Regeneron Research Site
state: Fukuoka
city: Nishinomiya
country: Japan
facility: Regeneron Research Site
state: Hyogo
city: Kanazawa
country: Japan
facility: Regeneron Research Site
state: Ishikawa
city: Suita
country: Japan
facility: Regeneron Research Site #3
state: Osaka
city: Suita
country: Japan
facility: Regeneron Research Site
state: Osaka
city: Osaka
country: Japan
facility: Regeneron Research Site
city: Amsterdam
country: Netherlands
facility: Regeneron Research Site
city: Rotterdam
country: Netherlands
facility: Regeneron Research Site
city: Parktown
country: South Africa
facility: Regeneron Research Site
state: Johannesburg
city: Ivano-Frankivs'k
country: Ukraine
facility: Regeneron Research Site
city: Kharkiv
country: Ukraine
facility: Regeneron Research Site
city: Kharkiv
country: Ukraine
facility: Regeneron Research Site #2
city: Kyiv
country: Ukraine
facility: Regeneron Research Site #2
city: Kyiv
country: Ukraine
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
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.