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

Regeneron Pharmaceuticals39 sites in 4 countries21 target enrollmentJuly 12, 2021

ConditionsHypertriglyceridemia

Interventionsevinacumab Placebo

Drugsevinacumab

Overview

Phase: Phase 2
Intervention: evinacumab
Conditions: Hypertriglyceridemia
Sponsor: Regeneron Pharmaceuticals
Enrollment: 21
Locations: 39
Primary Endpoint: Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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)

Registry

clinicaltrials.gov

Start Date

July 12, 2021

End Date

February 15, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Regeneron Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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

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

Arms & Interventions

evinacumab

Randomized 1:1

Intervention: evinacumab

Placebo

Randomized 1:1

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: Baseline to 52 weeks

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

Secondary Outcomes

Percent Change in Apolipoprotein B100 (ApoB100) Levels From Baseline to Week 52(Baseline to week 52)
Percent Change in Nuclear Magnetic Resonance (NMR)-Determined Particle Size and Number From Baseline to Week 52(Baseline to week 52)
Number of Independently Adjudicated Positive Episodes of Acute Pancreatitis (AP) Per Participant(Up to 52 weeks)
Number of Participants With Positive Neutralizing Antibodies (NAb)(Baseline to Week 52)
Percent Change in Fasting Low Density Lipoprotein (LDL-C) From Baseline to Week 52(Baseline to Week 52)
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)
Number of Participants With Positive Treatment-emergent Anti-Drug Antibodies (ADA)(Baseline to Week 52)
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) - (From Baseline to Week 52)(Baseline to week 52)
Number of Participants With TEAEs Based on Severity(From start of study drug administration up to off drug follow-up (up to Week 72))
Percent Change in Total Cholesterol (TC) - (Baseline to Week 52)(Baseline to week 52)
Percent Change in Apolipoprotein B48 (ApoB48) From Baseline to Week 52(Baseline to week 52)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs(From start of study drug administration up to off drug follow-up (up to Week 72))
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters(From start of study drug administration up to off drug follow-up (up to Week 72))
Percent Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52(Baseline to Week 52)
Concentration of Total Angiopoietin-like 3 (ANGPTL3) in Serum(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)
Concentration of Total Evinacumab in Serum(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)