Study of ARO-RAGE in Healthy Subjects and Patients With Inflammatory Lung Disease

Asthma Clinical Trial

Official title:

A Phase 1/2a Study Evaluating the Effects of ARO-RAGE Inhalation Solution in Healthy Subjects and Patients With Inflammatory Lung Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05276570
• Other study ID #: ARORAGE-1001
• Status: Recruiting
• Phase: Phase 1
• Start date: June 29, 2022
• Est. completion date: February 2025

Study information

• Verified date: June 2024
• Source: Arrowhead Pharmaceuticals
• Contact: Medical Monitor
• Phone: 626-304-3400
• Email: ARORAGE[@]arrowheadpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ARO-RAGE in normal healthy volunteers (NHVs) and in participants with inflammatory lung disease (asthma). In Part 1 of the study, NHVs will receive a single dose of ARO-RAGE or placebo. In Part 2 of the study, adult participants with asthma will receive 2 doses of ARO-RAGE or placebo. Additional NHVs may be randomized to receive 1 or 2 doses of ARO-RAGE or placebo at Sponsor discretion. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 149
• Est. completion date: February 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Normal pulmonary function tests at Screening (NHVs only)
• Confirmed diagnosis of asthma based on source verifiable medical record (asthma patients only)
• No abnormal finding of clinical relevance at Screening (other than asthma for asthma patients)
• Stable dose of asthma controller medications prior to Screening (asthma patients only)
• If on allergen-specific immunotherapy, participants must be on a stable maintenance dose
• Non-smoking
• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception. Males must not donate sperm during the study and for at least 12 weeks following the last dose of study drug
• Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

• Acute lower respiratory infection or asthma exacerbation within 30 days prior to first dose
• Positive COVID-19 test during Screening window
• Use of immunosuppressive medication within 90 days prior to first dose
• Receipt of any intranasal vaccine within 30 days prior to first dose
• Use of systemic corticosteroid therapy within 90 days prior to first dose
• Clinically significant health concerns (other than asthma in asthma patients)
• Human Immunodeficiency virus (HIV) infection, seropositive for Hepatitis B Virus (HBV), seropositive for Hepatitis C Virus (HCV)
• Uncontrolled hypertension
• Unwilling to limit alcohol consumption to within moderate limits for the duration of the study
• Use of illicit drugs
• Use of an investigational agent or device within 30 days prior to first dose Note: additional inclusion/exclusion criteria may apply per protocol

Related Conditions & MeSH terms

• Asthma
• Lung Diseases

Intervention

Drug:
• ARO-RAGE
single or multiple doses of ARO-RAGE by inhalation of nebulized solution
• Placebo
calculated volume to match active treatment by inhalation of nebulized solution

Locations

Country	Name	City	State
Australia	Institute for Respiratory Health-Perth	Nedlands	Western Australia
Australia	Mater Hospital	South Brisbane	Queensland
Korea, Republic of	Jeonbuk National University Hospital	Jeonju
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
New Zealand	New Zealand Clinical Research	Auckland
New Zealand	New Zealand Respiratory and Research Institute	Auckland
New Zealand	Pacific Clinical Research Network (PCRN)	Auckland
Poland	Prywatny Gabinet Internistyczno-Alergologiczny	Bialystok
Poland	Krakmed.NZOZ	Kraków
Poland	Medicome SP.ZO.O	Oswiecim
Spain	Pectus Respiratory Health	Barcelona
Thailand	Vajira Hospital	Bangkok
Thailand	Sriraj Hospital	Bangkok Noi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Korea, Republic of,  New Zealand,  Poland,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Secondary	Change from Baseline Over Time in Forced Expiratory Volume (FEV1)		Baseline through EOS (up to 113 days) or until serum soluble receptor for advance glycation end products (sRAGE) is = 70% of baseline value
Secondary	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
Secondary	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
Secondary	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 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	PK of ARO-RAGE: Time to Maximum Observed Plasma Concentration (Tmax)		single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	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 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	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 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	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 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	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 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	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 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	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 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Secondary	PK of ARO-RAGE: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae)		Through 24 hours post-dose
Secondary	PK of ARO-RAGE: Percentage of Administrated Drug Recovered in Urine Over 0 to 24 hours		Through 24 hours post-dose
Secondary	PK of ARO-RAGE: Renal Clearance (CLr)		single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma