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

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: NHV (Single Ascending Dose [SAD]): Pooled Placebo; a single dose of placebo was administered once on Day 1	Drug: Placebo; calculated volume to match active treatment by inhalation of nebulized solution
Experimental: NHV (SAD): ARO-MUC5AC 24 mg; a single dose of ARO-MUC5AC 24 mg was administered once on Day 1	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Experimental: NHV (SAD): ARO-MUC5AC 56 mg; a single dose of ARO-MUC5AC 56 mg was administered once on Day 1	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Experimental: NHV (SAD): ARO-MUC5AC 108 mg; a single dose of ARO-MUC5AC 108 mg was administered once on Day 1	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Experimental: NHV (SAD): ARO-MUC5AC 232 mg; a single dose of ARO-MUC5AC 232 mg was administered once on Day 1	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Placebo Comparator: NHV (Multiple Ascending Dose [MAD]): Pooled Placebo; 3 total doses of placebo were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: Placebo; calculated volume to match active treatment by inhalation of nebulized solution
Experimental: NHV (MAD): ARO-MUC5AC 24 mg; 3 total doses of ARO-MUC5AC 24 mg were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Experimental: NHV (MAD): ARO-MUC5AC 56 mg; 3 total doses of ARO-MUC5AC 56 mg were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Experimental: NHV (MAD): ARO-MUC5AC 108 mg; 3 total doses of ARO-MUC5AC 108 mg were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Placebo Comparator: Asthma Patients (MAD): Pooled Placebo; 3 total doses of placebo were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: Placebo; calculated volume to match active treatment by inhalation of nebulized solution
Experimental: Asthma Patients (MAD): ARO-MUC5AC 56 mg; 3 total doses of ARO-MUC5AC 56 mg were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Experimental: Asthma Patients (MAD): ARO-MUC5AC 108 mg; 3 total doses of ARO-MUC5AC 108 mg were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution
Placebo Comparator: COPD Patients (MAD): Pooled Placebo; 3 total doses of placebo were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: Placebo; calculated volume to match active treatment by inhalation of nebulized solution
Experimental: COPD Patients (MAD): 56 mg; 3 total doses of ARO-MUC5AC 56 mg were administered, with 1 dose given on each of Days 1, 15, and 29	Drug: ARO-MUC5AC; single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with treatment. TEAEs will be defined as AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. A serious AE (SAE) is an AE occurring during any study phase, and at any dose of study drug that: results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event that may jeopardize the subject or may require medical intervention to prevent one of the outcomes listed above.	From first dose of study drug up to Day 29 (single dose phase), and up to Day 85 (multiple dose phase)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Over Time From Baseline in Forced Expiratory Volume (FEV1), SAD Cohorts		Baseline, Day 1: 15, 60, 120 minutes (mins) post-dose, Days 2,3, 8, 15, 22, 29 (end of study [EOS])
Change Over Time From Baseline in FEV1, MAD Cohorts		Baseline, Day 1 (15, 60, 120 mins post-dose), Days 2, 3, 8, 15 (15, 60, 120 mins post-dose), 22, 29 (15, 60, 120 mins post-dose), 30, 35, 36, 43, 50, 57, 71, 85 (EOS)
Change Over Time From Baseline in Forced Vital Capacity (FVC), SAD Cohorts	Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose	Baseline, Day 1: 15, 60, 120 minutes (mins) post-dose, Days 2, 3, 8, 15, 22, 29 (end of study [EOS])
Change Over Time From Baseline in FVC, MAD Cohorts		Baseline, Day 1 (15, 60, 120 mins post-dose), Days 2, 8, 15 (15, 60, 120 mins post-dose), 22, 29 (15, 60, 120 mins post-dose), 30, 35, 36, 43, 50, 57, 71, 85 (EOS)
Pharmacokinetics (PK) of ARO-MUC5AC: Maximum Observed Plasma Concentration (Cmax), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose
PK of ARO-MUC5AC: Time to Cmax (Tmax), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose
PK of ARO-MUC5AC: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC0-t), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose
PK of ARO-MUC5AC: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose (based on start of inhalation)
PK of ARO-MUC5AC: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose
PK of ARO-MUC5AC: Terminal Elimination Half-Life (t1/2), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose
PK of ARO-MUC5AC: Apparent Systemic Clearance (CL/F), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose
PK of ARO-MUC5AC: Apparent Terminal-Phase Volume of Distribution (Vz/F), SAD Cohorts		Day 1: Predose, at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (based on start of inhalation); Day 2: 24 hours postdose; Day 3: 48 hours postdose
PK of ARO-MUC5AC: Recovery of Unchanged Drug in Urine Over 24 Hours (Amount Excreted; Ae), SAD Cohorts Only		Day 1: Predose and cumulatively from 0 to 6 hours and 6 to 24 hours postdose.
PK of ARO-MUC5AC: Fraction of Respirable Delivered Dose (RDD) Excreted Unchanged in Urine Over 24 Hours Postdose, as a Percentage (Fe), SAD Cohorts Only		Day 1: Predose and cumulatively from 0 to 6 hours and 6 to 24 hours postdose.
PK of ARO-MUC5AC: Renal Clearance (CLr), SAD Cohorts Only		Day 1: Predose and cumulatively from 0 to 6 hours and 6 to 24 hours postdose.
PK of ARO-MUC5AC: Maximum Observed Plasma Concentration (Cmax), MAD Cohorts		NHV Cohorts: Day 1: Predose, 0.5, 1, 2, 4, and 6 hours postdose (based on start of inhalation); Day 15: Predose; Day 29: Predose, 0.5, 1, 2, 4, and 6 hours postdose.
PK of ARO-MUC5AC: Tmax, MAD Cohorts		NHV Cohorts: Day 1: Predose, 0.5, 1, 2, 4, and 6 hours postdose (based on start of inhalation); Day 15: Predose; Day 29: Predose, 0.5, 1, 2, 4, and 6 hours postdose.
PK of ARO-MUC5AC: AUC0-t, MAD Cohorts		NHV Cohorts: Day 1: Predose, 0.5, 1, 2, 4, and 6 hours postdose (based on start of inhalation); Day 15: Predose; Day 29: Predose, 0.5, 1, 2, 4, and 6 hours postdose.

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 (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: August 19, 2026
• Last Verified: August 1, 2026

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