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

Hypertriglyceridemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04863014
• Other study ID #: R1500-HTG-20118
• Secondary ID: 2021-000437-13
• Status: Terminated
• Phase: Phase 2
• Start date: July 12, 2021
• Est. completion date: February 15, 2023

Study information

• Verified date: March 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: February 15, 2023
• Est. primary completion date: February 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertriglyceridemia
• Pancreatitis

Intervention

Drug:
• evinacumab
Intravenous infusion every 4 weeks (Q4W)

Other:
• Placebo
Intravenous infusion Q4W

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with at least 1 positively adjudicated acute pancreatitis (AP) episode		Up to 52 weeks
Secondary	Percent change in ApoC3		Baseline to week 52
Secondary	Percent change in fasting triglycerides (TGs)		Baseline to week 52
Secondary	Percent change in total cholesterol (TC)		Baseline to week 52
Secondary	Percent change in non-high-density lipoprotein cholesterol (non-HDL-C)		Baseline to week 52
Secondary	Percent change in ApoB48		Baseline to week 52
Secondary	Percent change in ApoB100 levels		Baseline to week 52
Secondary	Percent change in nuclear magnetic resonance (NMR)-determined particle size and number		Baseline to week 52
Secondary	Number of independently adjudicated episodes of AP per patient		Up to 52 weeks