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

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Hypertriglyceridemia

Intervention / Treatment
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* Drug: evinacumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: evinacumab<br>Randomized 1:1 | Drug: evinacumab<br>* Intravenous infusion every 4 weeks (Q4W)<br>* Other names: Evkeeza™;|
| Placebo Comparator: Placebo<br>Randomized 1:1 | Other: Placebo<br>* Intravenous infusion Q4W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with at least 1 positively adjudicated acute pancreatitis (AP) episode |  | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in ApoC3 |  | Baseline to week 52 | 
| Percent change in fasting triglycerides (TGs) |  | Baseline to week 52 | 
| Percent change in total cholesterol (TC) |  | Baseline to week 52 | 
| Percent change in non-high-density lipoprotein cholesterol (non-HDL-C) |  | Baseline to week 52 | 
| Percent change in ApoB48 |  | Baseline to week 52 | 
| Percent change in ApoB100 levels |  | Baseline to week 52 | 
| Percent change in nuclear magnetic resonance (NMR)-determined particle size and number |  | Baseline to week 52 | 
| Number of independently adjudicated episodes of AP per patient |  | Up to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe Hypertriglyceridemia (HTG), Recurrent Acute Pancreatitis