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NCT03399786

Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Completed Phase 3 Results posted Last updated 18 May 2021
What this trial tests

Phase 3 trial testing evinacumab in Homozygous Familial Hypercholesterolemia in 65 participants. Completed in 17 March 2020.

Timeline
18 January 2018
Primary endpoint
10 June 2019
17 March 2020

Quick facts

Lead sponsorRegeneron Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment65
Start date18 January 2018
Primary completion10 June 2019
Estimated completion17 March 2020
Sites30 locations across France, Italy, Japan, Netherlands, Greece, South Africa, Ukraine, Austria

Drugs / interventions tested

Conditions studied

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

12 and older, any sex, with Homozygous Familial Hypercholesterolemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Placebo IV Q4W1.9± 6.5
Evinacumab 15 mg/kg IV Q4W-47.1± 4.6
Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W-4.5± 4.8
Evinacumab 15 mg/kg IV Q4W-41.4± 3.3
Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W2.0± 5.4
Evinacumab 15 mg/kg IV Q4W-49.7± 3.8
Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W1.0± 4.2
Evinacumab 15 mg/kg IV Q4W-47.4± 3.0
Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W18.2
Evinacumab 15 mg/kg IV Q4W83.7
Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W4.5
Evinacumab 15 mg/kg IV Q4W55.8
Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W-2.6± 17.6
Evinacumab 15 mg/kg IV Q4W-134.7± 12.4
Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand) Secondary · 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 o

GroupValue95% CI
Placebo IV Q4W22.7
Evinacumab 15 mg/kg IV Q4W7.0
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) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W22.7
Evinacumab 15 mg/kg IV Q4W46.5
Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand) Secondary · 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 sub

GroupValue95% CI
Placebo IV Q4W77.3
Evinacumab 15 mg/kg IV Q4W32.6
Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W4.5
Evinacumab 15 mg/kg IV Q4W27.9
Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand) Secondary · 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).

GroupValue95% CI
Placebo IV Q4W-4.6± 7.0
Evinacumab 15 mg/kg IV Q4W-55.0± 3.1

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events (AEs) were collected from signature of the informed consent form up until end of study (Week 68) regardless of seriousness or relationship to investigational product (IP).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo IV Q4W (DBTP)
Serious: 0/21 (0%)
Deaths: 0/21
Evinacumab 15 mg/kg (DBTP)
Serious: 2/44 (5%)
Deaths: 0/44
Placebo IV Q4W (OLTP)
Serious: 0/20 (0%)
Deaths: 0/20
Evinacumab 15 mg/kg (OLTP)
Serious: 7/44 (16%)
Deaths: 0/44

Serious adverse events (13 terms)

ReactionSystemPlacebo IV Q4W (DBTP)Evinacumab 15 mg/kg (DBTP)Placebo IV Q4W (OLTP)Evinacumab 15 mg/kg (OLTP)
Acute myocardial infarctionCardiac disorders
Angina pectorisCardiac disorders
Angina unstableCardiac disorders
Cardiac failure congestiveCardiac disorders
Coronary artery diseaseCardiac disorders
GlaucomaEye disorders
PyelonephritisInfections and infestations
UrosepsisInfections and infestations
Cardiac procedure complicationInjury, poisoning and procedural complications
Carotid artery restenosisInjury, poisoning and procedural complications
Suicide attemptPsychiatric disorders
NephrocalcinosisRenal and urinary disorders
Aortic stenosisVascular disorders
Other adverse events (27 terms — click to expand)

ReactionSystemPlacebo IV Q4W (DBTP)Evinacumab 15 mg/kg (DBTP)Placebo IV Q4W (OLTP)Evinacumab 15 mg/kg (OLTP)
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Influenza like illnessGeneral disorders
NauseaGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Urinary tract infectionInfections and infestations
ToothacheGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
Gastroenteritis viralInfections and infestations
InfluenzaInfections and infestations
ConstipationGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Bacterial test positiveInvestigations
Serum ferritin decreasedInvestigations
Procedural headacheInjury, poisoning and procedural complications
Vaccination complicationInjury, poisoning and procedural complications
Dermatitis contactSkin and subcutaneous tissue disorders
Pruritus generalisedSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
AsthmaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Generalised anxiety disorderPsychiatric disorders
InsomniaPsychiatric disorders
HaematuriaRenal and urinary disorders
Menstrual discomfortReproductive system and breast disorders

Most-reported serious reactions: Acute myocardial infarction, Angina pectoris, Angina unstable, Cardiac failure congestive, Coronary artery disease, Glaucoma, Pyelonephritis, Urosepsis.

Data from ClinicalTrials.gov NCT03399786 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Evinacumab for Homozygous Familial Hypercholesterolemia.
    Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, et al · · 2020 · cited 577× · PMID 32813947 · DOI 10.1056/nejmoa2004215
  2. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  3. Antibodies to watch in 2022.
    Kaplon H, Chenoweth A, Crescioli S, Reichert JM. · · 2022 · cited 245× · PMID 35030985 · DOI 10.1080/19420862.2021.2014296
  4. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  5. Broadening the Scope of Dyslipidemia Therapy by Targeting APOC3 (Apolipoprotein C3) and ANGPTL3 (Angiopoietin-Like Protein 3).
    Ginsberg HN, Goldberg IJ. · · 2023 · cited 65× · PMID 36579649 · DOI 10.1161/atvbaha.122.317966
  6. Marked plaque regression in homozygous familial hypercholesterolemia.
    Reeskamp LF, Nurmohamed NS, Bom MJ, Planken RN, et al · · 2021 · cited 50× · PMID 34004483 · DOI 10.1016/j.atherosclerosis.2021.04.014
  7. Evinacumab in homozygous familial hypercholesterolaemia: long-term safety and efficacy.
    Gaudet D, Greber-Platzer S, Reeskamp LF, Iannuzzo G, et al · · 2024 · cited 47× · PMID 38856678 · DOI 10.1093/eurheartj/ehae325
  8. Evinacumab, an ANGPTL3 Inhibitor, in the Treatment of Dyslipidemia.
    Sosnowska B, Adach W, Surma S, Rosenson RS, et al · · 2022 · cited 35× · PMID 36614969 · DOI 10.3390/jcm12010168

Verify or expand the search:

Other trials of evinacumab

Trials testing the same drug.

Other recruiting trials for Homozygous Familial Hypercholesterolemia

Currently open trials in the same condition.

Other Regeneron Pharmaceuticals trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03399786.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing