Study of ARO-MUC5AC in Healthy Subjects and Patients With Muco-Obstructive Lung Disease

A Phase 1/2a Study Evaluating the Effects of ARO-MUC5AC Inhalation Solution in Healthy Subjects and Patients With Muco-Obstructive Lung Disease

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of ARO-MUC5AC in normal healthy volunteers (NHVs), patients with moderate-to-severe asthma and patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In part 1 NHVs will receive a single dose of ARO-MUC5AC or placebo. In part 2 of the study, NHVs, adult patients with asthma, and adult patients with COPD will receive 3 doses of ARO-MUC5AC or placebo.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease; Asthma
• Intervention / Treatment: Drug: ARO-MUC5AC; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Research Site 1
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Research Site 2
• New Zealand
  • Auckland, New Zealand, 1010
    • Research Site 1
  • Auckland, New Zealand, 1051
    • Research Site 2
• Poland
  • Bialystok, Poland, 15-010
    • Research Site 1
  • Krakow, Poland, 31-455
    • Research Site 2
  • Oświęcim, Poland, 32-600
    • Research Site 3
• South Korea
  • Jeonju, South Korea, 54907
    • Research Site 2
  • Seoul, South Korea, 04763
    • Research Site 1
  • Gyeonggi-do
    • Bucheon-si, Gyeonggi-do, South Korea, 14647
      • Research Site 3
• Spain
  • Barcelona, Spain, 08017
    • Research Site 1
• Thailand
  • Bangkok, Thailand, 10700
    • Research Site 1
• United Kingdom
  • Manchester
    • Wythenshawe, Manchester, United Kingdom, M23 9QZ
      • Research Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Normal pulmonary function tests at Screening (NHVs only)
• Confirmed diagnosis of asthma or COPD based on source verifiable medical record (asthma and COPD patients only)
• No abnormal finding of clinical relevance at Screening (NHVs only)
• Stable dose of asthma controller medications for at least 28 days prior to Screening (asthma patients only)
• Documented treatment with an inhaled corticosteroid and at least 1 additional maintenance asthma controller medication for at least 3 months prior to Screening (asthma patients only)
• Non-smoking (NHVs and asthma patients)
• Current smoker or ex-smoker with smoking history of ≥ 10 pack-years (COPD patients only)
• All COPD treatments have been stable for at least one month prior to Screening (COPD patients only)
• Able to produce an induced sputum sample at Screening
• 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 90 days 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 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
• Any history of chronic pulmonary disease (NHVs only)
• Any concomitant pulmonary disease in asthma or COPD patients that could interfere with the evaluation of the study drug or interpretation of patient safety or study results
• Use of theophylline within 30 days prior to first dose
• History of lung volume reduction surgery or pneumonectomy (COPD patients)
• Need for chronic oxygen support at Screening
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-MUC5AC; ARO-MUC5AC Inhalation	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Placebo Comparator: Placebo; (0.9% NaCl)	Drug: Placebo; calculated volume to match active treatment by inhalation of nebulized solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	single dose phase: up to Day 29; multiple dose phase: up to Day 85

Secondary Outcome Measures

Outcome Measure	Time Frame
Change Over Time from Baseline in Forced Expiratory Volume (FEV1)	single dose phase: up to Day 29; multiple dose phase: up to Day 85
Change Over Time from Baseline in Forced Vital Capacity (FVC)	single dose phase: up to Day 29; multiple dose phase: up to Day 85
PK of ARO-MUC5AC: Recovery of Unchanged Drug in Urine Over 24 Hours (Amount Excreted; Ae)	through 24 hours post-dose
PK of ARO-MUC5AC: Percentage of Administered Drug Recovered in Urine Over 0-24 Hours	through 24 hours post-dose
PK of ARO-MUC5AC: Maximum Observed Plasma Concentration (Cmax)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
PK of ARO-MUC5AC: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
PK of ARO-MUC5AC: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
PK of ARO-MUC5AC: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
PK of ARO-MUC5AC: Terminal Elimination Half-Life (t1/2)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
PK of ARO-MUC5AC: Apparent Systemic Clearance (CL/F)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
PK of ARO-MUC5AC: Apparent Terminal-Phase Volume of Distribution (VZ/F)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD
PK of ARO-MUC5AC: Renal Clearance (CLr)	single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs; and up to 6 hours post-dose on Days 1 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2022
• Primary Completion (Actual): November 12, 2024
• Study Completion (Actual): November 12, 2024

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Estimated): November 5, 2025
• Last Update Submitted That Met QC Criteria: November 3, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Asthma
• Other Study ID Numbers: AROMUC5AC-1001; 2022-003467-21 (EudraCT Number)

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