Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients

A Phase 1 Single and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-ANG3 in Adult Healthy Volunteers and in Dyslipidemic Patients

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetcs and pharmacodynamics of single- and multiple doses of ARO-ANG3 in healthy adult volunteers and in dyslipidemic patients including familial hypercholesterolemia and severe hypertriglyceridemia.

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Hypertriglyceridemia; Familial Hypercholesterolemia
• Intervention / Treatment: Drug: sterile normal saline (0.9% NaCl); Drug: ARO-ANG3

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Linear Clinical Research
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• New Zealand
  • Christchurch, New Zealand, 8011
    • Lipid & Diabetes Research Group
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies Limited
  • Aukland
    • Papatoetoe, Aukland, New Zealand, 2025
      • Middlemore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Women of child bearing 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
• On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study
• Normal electrocardiogram (ECG) at Screening

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-ANG3	Drug: ARO-ANG3; single or multiple doses of ARO-ANG3 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 113 (+/- 3 days) post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK) of ARO-ANG3: Maximum Observed Plasma Concentration (Cmax)	Single dose phase: Up to 48 hours post-dose
PK of ARO-ANG3: Time to Maximum Plasma Concentration (Tmax)	Single dose phase: Up to 48 hours post-dose
PK of ARO-ANG3: Terminal Elimination Half-Life (t1/2)	Single dose phase: Up to 48 hours post-dose
PK of ARO-ANG3: 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-ANG3: 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 ANGPTL3 from Pre-Dose Baseline	Baseline, Up to Day 113 (+/- 3 days)

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• Ying Q, Chan DC, Watts GF. Angiopoietin-like protein 3 inhibitors and contemporary unmet needs in lipid management. Curr Opin Lipidol. 2021 Jun 1;32(3):210-212. doi: 10.1097/MOL.0000000000000747. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Actual): May 17, 2021
• Study Completion (Actual): May 17, 2021

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 16, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Dyslipidemias; Hypercholesterolemia; Hypertriglyceridemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: AROANG1001

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