Asthma
Conditions
Brief 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.
Interventions
DRUGARO-RAGE
single or multiple doses of ARO-RAGE by inhalation of nebulized solution
DRUGPlacebo
calculated volume to match active treatment by inhalation of nebulized solution
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| 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) |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| PK of ARO-RAGE: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae) | Through 24 hours post-dose |
| PK of ARO-RAGE: Percentage of Administrated Drug Recovered in Urine Over 0 to 24 hours | Through 24 hours post-dose |
| 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 |
Countries
Australia, New Zealand, Poland, Spain, Thailand
Outcome results
None listed