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

Phase 2TerminatedNCT04863014

Regeneron Pharmaceuticals21 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hypertriglyceridemia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (39)

Radin Cardivascular Medical Group, Inc

Newport Beach, California, United States

Yale Cancer Center - Yale University

New Haven, Connecticut, United States

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, United States

Harmony Medical Research Institute, Inc.

Hialeah, Florida, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Outcomes

Primary Outcomes

Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode

All AP (Acute Pancreatitis) episodes occurred post-study drug treatment.

Time frame: Baseline to 52 weeks

Secondary Outcomes

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.