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

Study Overview
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Brief Summary
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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.

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

Conditions
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Asthma, Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: ARO-MUC5AC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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: Maximum Observed Plasma Concentration (Cmax) |  | single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 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, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 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, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 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, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 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, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 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, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 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, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD | 
| 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: Renal Clearance (CLr) |  | single dose phase: up to 48 Hours; multiple dose phase: up to 6 hours post-dose on Days 1, 15 and 29 for NHVs; and up to 6 hours post-dose on Days 1, 15 and 29, and up to 24 hours post-dose on Days 2 and 30 for participants with asthma or COPD |