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

Phase 2

Terminated

Conditions: Hypertriglyceridemia

Interventions: Drug: evinacumab
Other: Placebo

Registration Number: NCT04863014

Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary: 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 21

Inclusion Criteria

Adults without FCS due to LPL loss of function mutations
Documented history of 1 HTG-associated AP episode within 24 months of screening
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
Stable dose of lipid-lowering therapy (≥8 weeks) and willingness to maintain a stable regimen throughout the study
Body mass index ≥18.0 and ≤45.0 kg/m2
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

Hospitalization for AP within 4 weeks of screening
Known genetic FCS defined as homozygous or compound heterozygous LoF mutations in LPL as defined in the protocol
Symptomatic gallstone disease within 6 months prior to screening as defined in the protocol
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
Presence of any clinically significant, uncontrolled endocrine disease known to influence serum lipids as defined in the protocol
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
evinacumab	evinacumab	Randomized 1:1
Placebo	Placebo	Randomized 1:1

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 Positive Neutralizing Antibodies (NAb)	Baseline to Week 52	NAb positive was defined as presence of at least one positive nAb sample.
Percent Change in Fasting Low Density Lipoprotein (LDL-C) From Baseline to Week 52	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.
Percent Change in Apolipoprotein C3 (ApoC3) From Baseline to Week 52	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.
Percent Change in Fasting Triglycerides (TGs) - (From Baseline to Week 52)	Baseline to week 52
Number of Participants With Positive Treatment-emergent Anti-Drug Antibodies (ADA)	Baseline to Week 52	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.
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) - (From Baseline to Week 52)	Baseline to week 52
Number of Participants With TEAEs Based on Severity	From start of study drug administration up to off drug follow-up (up to Week 72)	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.
Percent Change in Total Cholesterol (TC) - (Baseline to Week 52)	Baseline to week 52
Percent Change in Apolipoprotein B48 (ApoB48) From Baseline to Week 52	Baseline to week 52
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 Clinically Significant Changes From Baseline in Laboratory Parameters	From start of study drug administration up to off drug follow-up (up to Week 72)	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.
Percent Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52	Baseline to Week 52	Percent Change in fasting HDL-C from Baseline to Week 52 was reported.
Concentration of Total Angiopoietin-like 3 (ANGPTL3) in Serum	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 ANGPTL3 in serum by time were analyzed and reported.
Concentration of Total Evinacumab in Serum	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 evinacumab in serum by time at Pre-dose and End of Infusion were analyzed and reported.

Trial Locations

Locations (39): Saint Louis University
🇺🇸
Saint Louis, Missouri, United States
Clinique des maladies lipidiques de Quebec
🇨🇦
Quebec, Canada
Excel Medical Clinical Trials, LLC
🇺🇸
Boca Raton, Florida, United States
Harmony Medical Research Institute, Inc.
🇺🇸
Hialeah, Florida, United States
NorthShore Medical Group
🇺🇸
Evanston, Illinois, United States
Advocate Medical Group Midwest Heart Specialists
🇺🇸
Park Ridge, Illinois, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
St. Vincent Medical Group, Inc.
🇺🇸
Carmel, Indiana, United States
Northwell Health
🇺🇸
Manhasset, New York, United States
University of Cincinnati Hospital
🇺🇸
Cincinnati, Ohio, United States
Penn Medicine: University of Pennsylvania Health System
🇺🇸
Philadelphia, Pennsylvania, United States
Methodist Dallas Medical Center
🇺🇸
Dallas, Texas, United States
West Virginia University Heart & Vascular Institute
🇺🇸
Morgantown, West Virginia, United States
Minneapolis Heart Institute
🇺🇸
Minneapolis, Minnesota, United States
Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
🇳🇱
Amsterdam, Netherlands
University Diabetes & Endocrine Consultants
🇺🇸
Chattanooga, Tennessee, United States
Ziekenhuis Rijnstate
🇳🇱
Arnhem, Netherlands
University of Washington
🇺🇸
Seattle, Washington, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
University Of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Radin Cardivascular Medical Group, Inc
🇺🇸
Newport Beach, California, United States
Northeast Georgia Medical Center
🇺🇸
Gainesville, Georgia, United States
Quincy Medical Group
🇺🇸
Quincy, Illinois, United States
Methodist Medical Center of Illiniois - UnityPoint Clinic
🇺🇸
Peoria, Illinois, United States
NYU Langone Hospital - Long Island
🇺🇸
Mineola, New York, United States
Mt Sinai - Ichan Medical Institute
🇺🇸
New York, New York, United States
Sante Clinical Research
🇺🇸
Kerrville, Texas, United States
MultiCare Institute for Research
🇺🇸
Spokane, Washington, United States
Centre Etudes Cliniques Ecogene-21
🇨🇦
Chicoutimi, Quebec, Canada
Robarts Research Institute
🇨🇦
London, Ontario, Canada
University Hospital Carl Gustav Carus
🇩🇪
Dresden, Germany
University Hospital of Leipzig
🇩🇪
Leipzig, Germany
Weill Cornell Medical College
🇺🇸
New York, New York, United States
Yale Cancer Center - Yale University
🇺🇸
New Haven, Connecticut, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Wisconsin Center for Advanced Research - a division of GI Associates, LLC
🇺🇸
Milwaukee, Wisconsin, United States
Johns Hopkins University School of Medicine
🇺🇸
Baltimore, Maryland, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States