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

Arrowhead Pharmaceuticals127 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

127

Conditions

Asthma

Interventions

ARO-RAGEDRUG

single or multiple doses of ARO-RAGE by inhalation of nebulized solution

PlaceboDRUG

calculated volume to match active treatment by inhalation of nebulized solution

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (8)

Research Site 1

Nedlands, Washington, Australia

Research Site 1

Auckland, New Zealand

Research Site 2

Auckland, New Zealand

Research Site 3

Auckland, New Zealand

Outcomes

Primary Outcomes

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)

Secondary Outcomes

Change from Baseline Over Time in Forced Expiratory Volume (FEV1)

Time frame: Baseline through EOS (up to 113 days) or until serum soluble receptor for advance glycation end products (sRAGE) is ≥ 70% of baseline value

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

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

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 29 for NHVs, and up to 24 hours post-dose for participants with asthma

PK of ARO-RAGE: Time to Maximum Observed Plasma Concentration (Tmax)

Time frame: 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

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 29 for NHVs, and up to 24 hours post-dose for participants with asthma

PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)

Data from ClinicalTrials.gov

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