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

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

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).

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia; Familial Chylomicronemia
• Intervention / Treatment: Drug: ARO-APOC3; Drug: sterile normal saline (0.9% NaCl)

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Research Site 2
  • Queensland
    • Sippy Downs, Queensland, Australia
      • Research Site 5
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site 3
  • Washington
    • Perth, Washington, Australia, 6009
      • Research Site 4
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5B7
      • Research Site 7
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Research Site 6
    • Montreal, Quebec, Canada, H2W 1R7
      • Research Site 8
• New Zealand
  • Christchurch, New Zealand, 8011
    • Research Site 11
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Research Site 9
    • Papatoetoe, Auckland, New Zealand, 2025
      • Research Site 10

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• Gaudet D, Clifton P, Sullivan D, Baker J, Schwabe C, Thackwray S, Scott R, Hamilton J, Given B, Melquist S, Zhou R, Chang T, San Martin J, Watts GF, Goldberg IJ, Knowles JW, Hegele RA, Ballantyne CM. RNA Interference Therapy Targeting Apolipoprotein C-III in Hypertriglyceridemia. NEJM Evid. 2023 Dec;2(12):EVIDoa2200325. doi: 10.1056/EVIDoa2200325. Epub 2023 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2019
• Primary Completion (Actual): February 11, 2021
• Study Completion (Actual): February 11, 2021

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Estimated): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hypertriglyceridemia; Hyperlipoproteinemia Type I
• Other Study ID Numbers: AROAPOC31001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes