The COMPASS Study: A Study of Volanesorsen (Formally ISIS-APOCIIIRx) in Patients With Hypertriglyceridemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 26 weeks in participants with Hypertriglyceridemia.

Official Title
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The COMPASS Study: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Hypertriglyceridemia

Conditions
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Hypertriglyceridemia

Intervention / Treatment
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* Drug: Volanesorsen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≤ 45 kg/m2 Fasting Triglycerides (TG) ≥ 500 mg/dL (≥ 5.7 mmol/L) at Screening. If on statin or fibrate, participants must be on stable, labeled dose for at least 3 months prior to screening. Participants not receiving these drugs within 4 weeks prior to screening are also eligible. Exclusion Criteria: Type 1 diabetes mellitus Newly diagnosed type 2 diabetes mellitus (within 12 weeks of screening) or HbA1c ≥ 9.0% at Screening Acute pancreatitis within 3 months of screening Acute Coronary Syndrome within 6 months of screening Major surgery within 3 months of screening Prior exposure to ISIS 304801 Have any other conditions in the opinion of the investigator which could interfere with the participant participating in or completing the study

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks. | Drug: Placebo<br>* Volanesorsen-matching placebo administered subcutaneously once-weekly for 26 weeks.<br>|
| Experimental: Volanesorsen 300 mg weekly<br>Volanesorsen 300 mg administered subcutaneously once-weekly for 26 weeks. | Drug: Volanesorsen<br>* 300 mg volanesorsen administered subcutaneously once-weekly for 26 weeks.<br>* Other names: ISIS 304801;|
| Experimental: Volanesorsen 300 mg biweekly, post Week 13<br>Volanesorsen 300 mg administered subcutaneously once-weekly for 13 weeks, then bi-weekly for 13 weeks. | Drug: Volanesorsen<br>* 300 mg volanesorsen administered subcutaneously once-weekly for 26 weeks.<br>* Other names: ISIS 304801;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3 |  | Baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Fasting TG From Baseline to Month 3 |  | Baseline to 3 months | 
| Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3 |  | Baseline to 3 months | 
| Percent Change in High-density Lipoprotein-cholesterol (HDL-C) From Baseline |  | Baseline to 3 months | 
| Treatment Response Rate Defined as Participants With Fasting TG < 150 mg/dL Reduction From Baseline at Month 3 | mg/dL = milligrams per deciliter | Baseline to 3 months | 
| Change From Baseline in Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) | HOMA-IR was calculated using the following formula: fasting insulin micro-international units per millimeter (μIU/mL) x fasting glucose mg/dL]/405. A negative change from baseline indicates improvement; a positive change from baseline indicates worsening. | Baseline to 3 and 6 months | 
| Change From Baseline in Glycated Hemoglobin (HbA1c) in Type 2 Diabetes Mellitus (T2DM) Participants |  | Baseline to 3 and 6 months |