Study of ARO-APOC3 in Healthy Volunteers, Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome (FCS)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).

Official Title
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A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome

Conditions
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Hypertriglyceridemia, Familial Chylomicronemia

Intervention / Treatment
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* Drug: ARO-APOC3
* Drug: sterile normal saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Normal electrocardiogram (ECG) at screening Hypertriglyceridemic patients must have a history of fasting serum triglycerides of at least 300 mg/dL (3.38 mmol/L) at screening or verifiable diagnosis of FCS Exclusion Criteria: Clinically significant health concerns Regular use of alcohol within one month prior to Screening Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study Recent use of illicit drugs Use of more than two tobacco/nicotine containing or cannabis products per month within 6 months prior to drug administration (applicable only to Normal Healthy Volunteers) Note: additional inclusion/exclusion criteria may apply, per protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARO-APOC3<br> | Drug: ARO-APOC3<br>* single or multiple doses of ARO-APOC3 by subcutaneous (sc) injections<br>|
| Placebo Comparator: Placebo<br> | Drug: sterile normal saline (0.9% NaCl)<br>* calculated volume to match active treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment |  | Up to Day 113 (+/- 3 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ARO-APOC3 in Normal Healthy Volunteers (NHVs): Maximum Observed Plasma Concentration (Cmax) |  | Single dose phase: Up to 48 hours post-dose | 
| PK of ARO-APOC3 in NHVs: Time to Maximum Plasma Concentration (Tmax) |  | Single dose phase: Up to 48 hours post-dose | 
| PK of ARO-APOC3 in NHVs: Terminal Elimination Half-Life (t1/2) |  | Single dose phase: Up to 48 hours post-dose | 
| PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) |  | Single dose phase: Up to 48 hours post-dose | 
| PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) |  | Single dose phase: Up to 48 hours post-dose | 
| Reduction in Fasting Serum APOC3 from Pre-Dose Baseline |  | Up to Day 113 (+/- 3 days) |