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

NCT04863014 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: R1500-HTG-201182021-000437-13
• Study Type: interventional
• Target: 21
• Locations: 4 countries
• Sites: 39

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)

Conditions

Hypertriglyceridemia

Keywords

Severe Hypertriglyceridemia (HTG); Recurrent Acute Pancreatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• Percent Change in Apolipoprotein C3 (ApoC3) From Baseline to Week 52

  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

Study Arms (2)

evinacumab

EXPERIMENTAL

Randomized 1:1

Drug: evinacumab

Placebo

PLACEBO COMPARATOR

Randomized 1:1

Other: Placebo

Interventions

evinacumab DRUG

Intravenous infusion every 4 weeks (Q4W)

Also known as: REGN1500, Evkeeza™

evinacumab

Placebo OTHER

Intravenous infusion Q4W

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (39)

Radin Cardivascular Medical Group, Inc

Newport Beach, California, 92663, United States

Location

Yale Cancer Center - Yale University

New Haven, Connecticut, 06510, United States

Location

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, 33434, United States

Location

Harmony Medical Research Institute, Inc.

Hialeah, Florida, 33015, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

NorthShore Medical Group

Evanston, Illinois, 60201, United States

Location

Advocate Medical Group Midwest Heart Specialists

Park Ridge, Illinois, 60068, United States

Location

Methodist Medical Center of Illiniois - UnityPoint Clinic

Peoria, Illinois, 61636, United States

Location

Quincy Medical Group

Quincy, Illinois, 62301, United States

Location

St. Vincent Medical Group, Inc.

Carmel, Indiana, 46290, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55422, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Mt Sinai - Ichan Medical Institute

New York, New York, 10029, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati Hospital

Cincinnati, Ohio, 45267, United States

Location

Penn Medicine: University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

University Of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University Diabetes & Endocrine Consultants

Chattanooga, Tennessee, 37411, United States

Location

Methodist Dallas Medical Center

Dallas, Texas, 75208, United States

Location

Sante Clinical Research

Kerrville, Texas, 78028, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MultiCare Institute for Research

Spokane, Washington, 99202, United States

Location

West Virginia University Heart & Vascular Institute

Morgantown, West Virginia, 26506, United States

Location

Wisconsin Center for Advanced Research - a division of GI Associates, LLC

Milwaukee, Wisconsin, 53215, United States

Location

Robarts Research Institute

London, Ontario, N6A 5B7, Canada

Location

Centre Etudes Cliniques Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Clinique des maladies lipidiques de Quebec

Québec, G1V 4W2, Canada

Location

University Hospital Carl Gustav Carus

Dresden, 01307, Germany

Location

University Hospital of Leipzig

Leipzig, 04103, Germany

Location

Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)

Amsterdam, 1105 AZ, Netherlands

Location

Ziekenhuis Rijnstate

Arnhem, 6815 AD, Netherlands

Location

MeSH Terms

Conditions

Hypertriglyceridemia; Pancreatitis

Interventions

evinacumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases

Limitations and Caveats

The sponsor terminated the study early due to enrollment issues.

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

8447346643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 28, 2021
• Study Start: July 12, 2021
• Primary Completion: February 15, 2023
• Study Completion: February 15, 2023
• Last Updated: May 22, 2024
• Results First Posted: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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

Locations

CA (3); DE (2); US (32); NL (2)