Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia

Study Overview
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Brief Summary
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The purpose of AROAPOC3-2001 is to evaluate the efficacy and safety of ARO-APOC3 in participants with severe hypertriglyceridemia. Participants will receive 2 subcutaneous injections of ARO-APOC3.

Official Title
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A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Severe Hypertriglyceridemia

Conditions
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Severe Hypertriglyceridemia

Intervention / Treatment
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* Drug: ARO-APOC3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Based on medical history, evidence of TG ≥ 500 mg/dL and ≤ 4000 mg/dL at Screening Fasting TG ≥ 500 mg/dL at Screening Willing to follow diet counseling per Investigator judgment based on local standard of care Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception Willing to provide written informed consent and to comply with study requirements Exclusion Criteria: Active pancreatitis within 12 weeks prior to first dose Any planned bariatric surgery or similar procedures to induce weight loss from consent to end of study Acute coronary syndrome event within 24 weeks of first dose Major surgery within 12 weeks of first dose Planned coronary intervention (e.g., stent placement or heart bypass) or any non-cardiac major surgical procedure throughout the study Uncontrolled hypertension Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV), seropositive for Hepatitis C (HCV) Uncontrolled hypothyroidism or hyperthyroidism Hemorrhagic stroke within 24 weeks of first dose Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply) Note: additional inclusion/exclusion criteria may apply per protocol

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 |
| --- | --- |
| Experimental: ARO-APOC3<br>ARO-APOC3 Injection | Drug: ARO-APOC3<br>* 2 doses of ARO-APOC3 by subcutaneous (sc) injection<br>|
| Placebo Comparator: Placebo<br>Sterile Normal Saline (0.9% NaCl) | Drug: Placebo<br>* calculated volume to match active treatment by sc 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 Triglycerides (TG) at Week 24 |  | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Fasting TG Over Time Through Week 48 |  | Baseline, up to Week 48 | 
| Percent Change from Baseline in Apolipoprotein (Apo)C-III at Week 24 |  | Baseline, Week 24 | 
| Percent Change from Baseline in ApoC-III Over Time Through Week 48 |  | Baseline, up to Week 48 | 
| Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 |  | Baseline, Week 24 | 
| Percent Change from Baseline in Fasting Non-HDL-C Over Time Through Week 48 |  | Baseline, up to Week 48 | 
| Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 |  | Baseline, Week 24 | 
| Percent Change from Baseline in Fasting HDL-C Over Time Through Week 48 |  | Baseline, up to Week 48 | 
| Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 |  | Baseline, Week 24 | 
| Percent Change from Baseline in Fasting Total ApoB Over Time Through Week 48 |  | Baseline, up to Week 48 | 
| Percent Change from Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation |  | Baseline, Week 24 | 
| Percent Change from Baseline in Fasting LDL-C Using Ultracentrifugation Over Time Through Week 48 |  | Baseline, up to Week 48 | 
| Change from Baseline in Plasma Concentration of ARO-APOC3 Over Time Through Week 48 |  | Baseline, up to Week 48 | 
| Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) Possibly or Probably Related to Treatment |  | up to Week 48 |