Efficacy and Safety of Evinacumab in Adult Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis

The primary objective of the study is to determine the proportion of patients with elevated triglycerides (TG), without familial chylomicronemia syndrome (FCS) due to loss of function (LoF) mutations in lipoprotein lipase (LPL), and a history of hypertriglyceridemia (HTG)-associated acute pancreatitis (AP) who experience a recurrent episode of AP after treatment with evinacumab versus placebo.

The secondary objectives of the study are:

• To determine the change in the standard lipid profile after therapy with evinacumab versus placebo
• To determine the changes in specialty lipoprotein parameters (ApoC3, ApoB48, ApoB100, and nuclear magnetic resonance [NMR] lipid profile) after therapy with evinacumab versus placebo
• To measure the number of AP episodes per patient
• To assess the safety and tolerability of evinacumab
• To assess the potential immunogenicity of evinacumab
• To assess the concentrations of total evinacumab and total angiopoietin-like 3 (ANGPTL3)

Study Overview

• Status: Terminated
• Conditions: Hypertriglyceridemia
• Intervention / Treatment: Drug: evinacumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4W2
    • Clinique des maladies lipidiques de Quebec
  • Ontario
    • London, Ontario, Canada, N6A 5B7
      • Robarts Research Institute
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Centre Etudes Cliniques Ecogene-21
• Germany
  • Dresden, Germany, 01307
    • University Hospital Carl Gustav Carus
  • Leipzig, Germany, 04103
    • University Hospital of Leipzig
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
  • Arnhem, Netherlands, 6815 AD
    • Ziekenhuis Rijnstate
• United States
  • California
    • Newport Beach, California, United States, 92663
      • Radin Cardivascular Medical Group, Inc
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center - Yale University
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC
    • Hialeah, Florida, United States, 33015
      • Harmony Medical Research Institute, Inc.
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore Medical Group
    • Park Ridge, Illinois, United States, 60068
      • Advocate Medical Group Midwest Heart Specialists
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illiniois - UnityPoint Clinic
    • Quincy, Illinois, United States, 62301
      • Quincy Medical Group
  • Indiana
    • Carmel, Indiana, United States, 46290
      • St. Vincent Medical Group, Inc.
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Minneapolis, Minnesota, United States, 55422
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital - Long Island
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10029
      • Mt Sinai - Ichan Medical Institute
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine: University of Pennsylvania Health System
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes & Endocrine Consultants
  • Texas
    • Dallas, Texas, United States, 75208
      • Methodist Dallas Medical Center
    • Kerrville, Texas, United States, 78028
      • Sante Clinical Research
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington
    • Spokane, Washington, United States, 99202
      • MultiCare Institute for Research
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Heart & Vascular Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research - a division of GI Associates, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Adults without FCS due to LPL loss of function mutations
2. Documented history of 1 HTG-associated AP episode within 24 months of screening
3. Fasting serum TG value >880 mg/dL (10 mmol/L) or >500 mg/dL (5.6mmol/L) determined during the screening period as described in the protocol
4. Stable dose of lipid-lowering therapy (≥8 weeks) and willingness to maintain a stable regimen throughout the study
5. Body mass index ≥18.0 and ≤45.0 kg/m2
6. Compliance with a stable diet and exercise regimen at screening and willingness to continue the diet through the end of the study

Key Exclusion Criteria:

1. Hospitalization for AP within 4 weeks of screening
2. Known genetic FCS defined as homozygous or compound heterozygous LoF mutations in LPL as defined in the protocol
3. Symptomatic gallstone disease within 6 months prior to screening as defined in the protocol
4. Use of any medication or nutraceutical known to alter serum lipids which has not been part of a stable therapeutic regimen for at least 8 weeks, and there are no plans to change the regimen during the study
5. Presence of any clinically significant, uncontrolled endocrine disease known to influence serum lipids as defined in the protocol
6. Has received a COVID-19 vaccination within 1-week of planned start medication or for which the planned COVID-19 vaccination would not be completed 1-week prior to start of the study

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Randomized 1:1	Other: Placebo; Intravenous infusion Q4W
Experimental: evinacumab; Randomized 1:1	Drug: evinacumab; Intravenous infusion every 4 weeks (Q4W); Other Names: REGN1500; Evkeeza™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode	All AP (Acute Pancreatitis) episodes occurred post-study drug treatment.	Baseline to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Apolipoprotein C3 (ApoC3) From Baseline to Week 52	Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoC3 was a component of very-low-density lipoproteins (VLDL), high-density lipoprotein (HDL), and triglyceride-rich chylomicrons and regulates lipid metabolism. Percent change in ApoC3 from Baseline to Week 52 was reported.	Baseline to week 52
Percent Change in Fasting Triglycerides (TGs) - (From Baseline to Week 52)		Baseline to week 52
Percent Change in Total Cholesterol (TC) - (Baseline to Week 52)		Baseline to week 52
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) - (From Baseline to Week 52)		Baseline to week 52
Percent Change in Apolipoprotein B48 (ApoB48) From Baseline to Week 52		Baseline to week 52
Percent Change in Apolipoprotein B100 (ApoB100) Levels From Baseline to Week 52		Baseline to week 52
Percent Change in Nuclear Magnetic Resonance (NMR)-Determined Particle Size and Number From Baseline to Week 52		Baseline to week 52
Number of Independently Adjudicated Positive Episodes of Acute Pancreatitis (AP) Per Participant		Up to 52 weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs		From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With TEAEs Based on Severity	AE was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. TEAEs are defined as AEs that developed or worsened during the treatment period. Severity of TEAEs was graded according to the following scale: Mild: Does not interfere in a significant manner with the participants normal functioning level, Moderate: Produces some impairment of functioning but is not hazardous to health and Severe: Produces significant impairment of functioning or incapacitation and is a definite hazard to the participants health.	From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters	Clinical laboratory parameters included biochemistry, hematology and urinalysis. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.	From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With Positive Treatment-emergent Anti-Drug Antibodies (ADA)	Treatment-Emergent ADA was defined as any positive post baseline assay response when baseline results were negative or missing. Treatment-Emergent ADA responses were further classified as: Persistent (a positive result in the ADA assay detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period [based on] nominal sampling time], with no ADA-negative results in-between, regardless of any missing samples); Indeterminate (a positive result in the ADA assay at the last collection time point only, regardless of any missing samples); Transient (not persistent/indeterminate, regardless of any missing samples). Number of participants with positive treatment-emergent ADA response during Week 52 were reported.	Baseline to Week 52
Number of Participants With Positive Neutralizing Antibodies (NAb)	NAb positive was defined as presence of at least one positive nAb sample.	Baseline to Week 52
Percent Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52	Percent Change in fasting HDL-C from Baseline to Week 52 was reported.	Baseline to Week 52
Percent Change in Fasting Low Density Lipoprotein (LDL-C) From Baseline to Week 52	LDL-C levels were determined in beta-quantification with ultracentrifugation method. Percent change in fasting LDL-C from Baseline to Week 52 was reported.	Baseline to Week 52
Concentration of Total Evinacumab in Serum	Concentration of total evinacumab in serum by time at Pre-dose and End of Infusion were analyzed and reported.	Pre-dose and End of Infusion (EOI) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44, and 48; Pre-dose at Weeks 28 and 52
Concentration of Total Angiopoietin-like 3 (ANGPTL3) in Serum	Concentration of total ANGPTL3 in serum by time were analyzed and reported.	Pre-dose and End of Infusion (EOI) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44, and 48; Pre-dose at Weeks 28 and 52

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Actual): February 15, 2023
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Severe Hypertriglyceridemia (HTG); Recurrent Acute Pancreatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Pancreatic Diseases; Pancreatitis; Hypertriglyceridemia
• Other Study ID Numbers: R1500-HTG-20118; 2021-000437-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No