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

Regeneron Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Hypertriglyceridemia

Treatments: Other: Placebo; Drug: evinacumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04863014

R1500-HTG-20118

2021-000437-13 (EudraCT Number)

Details and patient eligibility

About

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)

Enrollment: 21 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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21 participants in 2 patient groups, including a placebo group

evinacumab

Experimental group

Description:

Randomized 1:1

Treatment:

Drug: evinacumab

Placebo

Placebo Comparator group

Description:

Randomized 1:1

Treatment:

Other: Placebo