Study of ARO-RAGE in Healthy Subjects

A Phase 1 Study Evaluating the Effects of ARO-RAGE Injection for Subcutaneous Administration in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-RAGE Injection in normal healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: ARO-RAGE Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Aukland
    • Grafton, Aukland, New Zealand, 1010
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Normal pulmonary function tests at Screening prior to sputum induction
• Normal 12-lead electrocardiogram (ECG) at Screening
• Non-smoking
• Able to produce an induced sputum sample at Screening
• Participants of child-bearing potential (male and female) must use highly effective contraception and cannot donate sperm or eggs during the study or for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Women must have a negative pregnancy test and cannot be breastfeeding
• Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

• Acute lower respiratory infection within 30 days prior to first dose and/or acute upper respiratory infection within 7 days prior to first dose
• Positive COVID-19 test during Screening window
• Chronic or acute infection that is clinically significant or requires treatment with systemic antibiotics, antivirals, antifungals, or antiparasitics within 30 days prior to first dose
• Any history of chronic pulmonary disease
• Use of immunosuppressive medication within 90 days prior to first dose
• Receipt of any intranasal vaccine within 30 days prior to first dose
• Human Immunodeficiency virus (HIV) infection, seropositive fo Hepatitis B Virus (HBV), seropositive for Hepatitis C Virus (HCV)
• Uncontrolled hypertension
• Use of illicit drugs
• Unwilling to limit alcohol consumption to within moderate limits for the duration of the study
• Use of an investigational agent or device within 30 days prior to first dose
• Prior use of any formulation of ARO-RAGE

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: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-RAGE; single or multiple doses of ARO-RAGE by subcutaneous (sc) injection	Drug: ARO-RAGE Injection; ARO-RAGE injection for sc administration
Placebo Comparator: Placebo; placebo calculated volume to match active treatment by sc injection	Drug: Placebo; normal saline (0.9% NaCl) by sc injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	From first dose of study drug through the end of study (EOS; up to 113 days or until serum soluble receptor for advance glycation end products [SRAGE] is ≥70% of baseline value, whichever is later)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline Over Time in Forced Expiratory Volume (FEV1)	Baseline through EOS (up to 113 days or until serum SRAGE is ≥70% of baseline value, whichever is later)
Change from Baseline Over Time in Forced Vital Capacity (FVC)	Baseline through EOS (up to 113 days or until serum SRAGE is ≥70% of baseline value, whichever is later)
Change from Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO)	Baseline through EOS (up to 113 days or until serum SRAGE is ≥70% of baseline value, whichever is later)
PK of ARO-RAGE: Maximum Observed Plasma Concentration (Cmax)	single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24)	single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)	single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf)	single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29
PK of ARO-RAGE: Terminal Elimination Half-Life (t1/2)	single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29
PK of ARO-RAGE: Apparent Systemic Clearance (CL/F)	single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29
PK of ARO-RAGE: Apparent Terminal-Phase Volume of Distribution (VZ/F)	single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2022
• Primary Completion (Actual): February 8, 2024
• Study Completion (Actual): February 8, 2024

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ARORAGE-1002

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