Clinical trial NCT04863014: Efficacy and Safety of Evinacumab in Adult Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hypertriglyceridemia
Keywords: Severe Hypertriglyceridemia (HTG)
Recurrent Acute Pancreatitis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-04-28
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: 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 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)


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode
timeFrame: Baseline to 52 weeks
Secondary outcomes:
measure: Percent Change in Apolipoprotein C3 (ApoC3) From Baseline to Week 52
timeFrame: Baseline to week 52
measure: Percent Change in Fasting Triglycerides (TGs) - (From Baseline to Week 52)
timeFrame: Baseline to week 52
measure: Percent Change in Total Cholesterol (TC) - (Baseline to Week 52)
timeFrame: Baseline to week 52
measure: Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) - (From Baseline to Week 52)
timeFrame: Baseline to week 52
measure: Percent Change in Apolipoprotein B48 (ApoB48) From Baseline to Week 52
timeFrame: Baseline to week 52
measure: Percent Change in Apolipoprotein B100 (ApoB100) Levels From Baseline to Week 52
timeFrame: Baseline to week 52
measure: Percent Change in Nuclear Magnetic Resonance (NMR)-Determined Particle Size and Number From Baseline to Week 52
timeFrame: Baseline to week 52
measure: Number of Independently Adjudicated Positive Episodes of Acute Pancreatitis (AP) Per Participant
timeFrame: Up to 52 weeks
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From start of study drug administration up to off drug follow-up (up to Week 72)
measure: Number of Participants With TEAEs Based on Severity
timeFrame: From start of study drug administration up to off drug follow-up (up to Week 72)
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
timeFrame: From start of study drug administration up to off drug follow-up (up to Week 72)
measure: Number of Participants With Positive Treatment-emergent Anti-Drug Antibodies (ADA)
timeFrame: Baseline to Week 52
measure: Number of Participants With Positive Neutralizing Antibodies (NAb)
timeFrame: Baseline to Week 52
measure: Percent Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52
timeFrame: Baseline to Week 52
measure: Percent Change in Fasting Low Density Lipoprotein (LDL-C) From Baseline to Week 52
timeFrame: Baseline to Week 52
measure: Concentration of Total Evinacumab in Serum
timeFrame: 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
measure: Concentration of Total Angiopoietin-like 3 (ANGPTL3) in Serum
timeFrame: 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
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Radin Cardivascular Medical Group, Inc
state: California
city: New Haven
country: United States
facility: Yale Cancer Center - Yale University
state: Connecticut
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Hialeah
country: United States
facility: Harmony Medical Research Institute, Inc.
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Evanston
country: United States
facility: NorthShore Medical Group
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Medical Group Midwest Heart Specialists
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illiniois - UnityPoint Clinic
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: Carmel
country: United States
facility: St. Vincent Medical Group, Inc.
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Mt Sinai - Ichan Medical Institute
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Kerrville
country: United States
facility: Sante Clinical Research
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: MultiCare Institute for Research
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Heart & Vascular Institute
state: West Virginia
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research - a division of GI Associates, LLC
state: Wisconsin
city: London
country: Canada
facility: Robarts Research Institute
state: Ontario
city: Chicoutimi
country: Canada
facility: Centre Etudes Cliniques Ecogene-21
state: Quebec
city: Quebec
country: Canada
facility: Clinique des maladies lipidiques de Quebec
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Leipzig
country: Germany
facility: University Hospital of Leipzig
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: