To Evaluate the Efficacy and Safety of Pegozafermin in Subjects With Severe Hypertriglyceridemia

Study Overview
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Brief Summary
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To determine the effect of Pegozafermin on fasting serum triglyceride levels in subjects with Severe Hypertriglyceridemia (TG ≥500 to ≤2000 mg/dL) after 26 weeks of treatment.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pegozafermin in Subjects With Severe Hypertriglyceridemia (SHTG): The ENTRUST Study

Conditions
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Severe Hypertriglyceridemia

Intervention / Treatment
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* Drug: Pegozafermin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥22 years Willing to enter a lifestyle optimization period during the screening period and willing to maintain those eating and exercise habits for the duration of the study Subjects should be on stable background standard-of-care Lipid Modifying Therapy (LMT) Exclusion Criteria: Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Uncontrolled or newly diagnosed (≤3 months since diagnosis) Type 2 diabetes mellitus as determined by the Principal Investigator. Subjects must have HbA1c level ≤9.5% at Screening. Medications for glucose management must be stable for at least 4 weeks prior to Screening Type 1 diabetes mellitus A history of symptomatic gallstone disease (unless treated with cholecystectomy), or any other ongoing symptomatic biliary disease Acute pancreatitis within 6 months prior to Screening Subjects with chronic pancreatitis Known or suspected familial chylomicronemia syndrome (FCS) (Type 1 hyperlipoproteinemia) Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 22 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: Pegozafermin - 30mg once a week<br> | Drug: Pegozafermin<br>* Subcutaneous injection<br>|
| Experimental: Pegozafermin - 20mg once a week<br> | Drug: Pegozafermin<br>* Subcutaneous injection<br>|
| Placebo Comparator: Placebo once a week<br> | Drug: Placebo<br>* Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in fasting TG |  | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C) |  | 26 weeks | 
| Percent change from baseline in high-density lipoprotein cholesterol (HDL-C) |  | 26 weeks | 
| Percent change from baseline in very low-density lipoprotein cholesterol (VLDL-C) |  | 26 weeks | 
| Percent change from baseline in total cholesterol (TC) |  | 26 weeks | 
| Change from baseline in liver fat by magnetic resonance imaging - whole liver proton density fat fraction (MRI-PDFF) |  | 26 weeks | 
| Percent change from baseline in apolipoprotein B (apo-B) |  | 26 weeks | 
| Change in HbA1c at Week 26 for those with baseline ≥6.5% |  | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHTG, Hypertriglyceridemia, Metabolic diseases, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders