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Phase 3 N=65 Randomized Quadruple-blind Treatment

Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Homozygous Familial Hypercholesterolemia

Enrolled (actual)
65
Serious AEs
7.0%
Results posted
May 2021
Primary outcome: Primary: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand) — 1.9; -47.1 Percent Change — p=< 0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
evinacumab (Drug); Placebo (Drug)
Age
Pediatric, Adult, Older Adult · 12+ yrs
Sex
All
Sponsor
Regeneron Pharmaceuticals
Primary completion
Jun 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand)
1.9; -47.1 < 0.0001 sig
SECONDARY
Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
-4.5; -41.4 < 0.0001 sig
SECONDARY
Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
2.0; -49.7 < 0.0001 sig
SECONDARY
Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
1.0; -47.4 < 0.0001 sig
SECONDARY
Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
18.2; 83.7 < 0.0001 sig
SECONDARY
Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
4.5; 55.8 = 0.0028 sig
SECONDARY
Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand)
-2.6; -134.7 < 0.0001 sig
SECONDARY
Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
22.7; 7.0 = 0.0845
SECONDARY
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)
22.7; 46.5 = 0.0203 sig
SECONDARY
Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
77.3; 32.6 = 0.0004 sig
SECONDARY
Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand)
4.5; 27.9
SECONDARY
Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand)
-4.6; -55.0
SECONDARY
Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand)
-3.6; -5.5
SECONDARY
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
-8.0; -74.4
SECONDARY
Absolute Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
-0.4; -148.0
SECONDARY
Absolute Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
-0.4; -161.6
SECONDARY
Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline to Week 24 (ITT Estimand)
5.8; -84.1

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

  • 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 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03399786). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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