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

Phase 2TerminatedNCT05292950

Arrowhead Pharmaceuticals78 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Asthma Chronic Obstructive Pulmonary Disease

Interventions

ARO-MUC5ACDRUG

single or multiple doses of ARO- MUC5AC by inhalation of nebulized solution

PlaceboDRUG

calculated volume to match active treatment by inhalation of nebulized solution

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (13)

Research Site 2

South Brisbane, Queensland, Australia

Research Site 1

Nedlands, Australia

Research Site 1

Auckland, New Zealand

Outcomes

Primary Outcomes

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.

Time frame: From first dose of study drug up to Day 29 (single dose phase), and up to Day 85 (multiple dose phase)

Secondary Outcomes

Change Over Time From Baseline in Forced Expiratory Volume (FEV1), SAD Cohorts

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Data from ClinicalTrials.gov

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