Study of ARO-RAGE in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT05533294
• Recruitment Status: Completed
• First Posted: September 9, 2022
• Last Update Posted: March 29, 2024
• Sponsor: Arrowhead Pharmaceuticals
• Information provided by (Responsible Party): Arrowhead Pharmaceuticals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: ARO-RAGE Injection; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study Evaluating the Effects of ARO-RAGE Injection for Subcutaneous Administration in Healthy Subjects
• Actual Study Start Date: November 29, 2022
• Actual Primary Completion Date: February 8, 2024
• Actual Study Completion Date: February 8, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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 :

1. Change from Baseline Over Time in Forced Expiratory Volume (FEV1) [ Time Frame: Baseline through EOS (up to 113 days or until serum SRAGE is ≥70% of baseline value, whichever is later) ]
2. Change from Baseline Over Time in Forced Vital Capacity (FVC) [ Time Frame: Baseline through EOS (up to 113 days or until serum SRAGE is ≥70% of baseline value, whichever is later) ]
3. Change from Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO) [ Time Frame: Baseline through EOS (up to 113 days or until serum SRAGE is ≥70% of baseline value, whichever is later) ]
4. PK of ARO-RAGE: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 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 ]
5. PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24) [ Time Frame: 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 ]
6. PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast) [ Time Frame: 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 ]
7. PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf) [ Time Frame: 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 ]
8. PK of ARO-RAGE: Terminal Elimination Half-Life (t1/2) [ Time Frame: 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 ]
9. PK of ARO-RAGE: Apparent Systemic Clearance (CL/F) [ Time Frame: 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 ]
10. PK of ARO-RAGE: Apparent Terminal-Phase Volume of Distribution (VZ/F) [ Time Frame: 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 ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

New Zealand

Research Site

Grafton, Aukland, New Zealand, 1010

Sponsors and Collaborators

Arrowhead Pharmaceuticals

More Information

• Responsible Party: Arrowhead Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05533294
• Other Study ID Numbers: ARORAGE-1002
• First Posted: September 9, 2022
• Last Update Posted: March 29, 2024
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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