Study of ARO-MMP7 Inhalation Solution in Healthy Subjects and Patients With Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-MMP7 in normal healthy volunteers (NHVs) and in participants with idiopathic pulmonary fibrosis (IPF). The study will initiate with NHVs receiving single ascending doses of ARO-MMP7. Following evaluation of safety and pharmacodynamic (PD) data, participants will receive multiple doses of ARO-MMP7.

Official Title
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A Phase 1/2a Study Evaluating the Effects of ARO-MMP7 Inhalation Solution in Healthy Subjects and Patients With Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: ARO-MMP7 Inhalation Solution
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (NHVs): Normal pulmonary function tests at Screening Normal electrocardiogram (ECG) at Screening Non-smoking Female participants cannot be pregnant or lactating Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later. Inclusion Criteria (IPF Participants): Age ≥ 45 years at Screening Clinical diagnosis consistent with IPF based upon established criteria confirmed by review of high-resolution computed tomography (HRCT) and surgical lung biopsy findings (if available) Safely able to undergo bronchoscopy Stable IPF disease at Screening with minimum life expectancy of ≥ 12 months from Screening Female participants cannot be pregnant or lactating Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later. Exclusion Criteria (NHVs): Acute lower respiratory infection within 30 days prior to first dose 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 or anaphylaxis Human immunodeficiency virus (HIV) infection, seropositive for hepatitis B virus (HBV), seropositive for hepatitis C virus (HCV) Uncontrolled hypertension History of significant cardiac disease History of major surgery within 12 weeks prior to first dose 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 Exclusion Criteria (IPF Participants): Interstitial lung disease (ILD) associated with known primary cause Positive COVID-19 test during Screening window IPF exacerbation within 6 weeks prior to first dose Lower respiratory tract infection requiring antibiotics or antivirals within 30 days prior to first dose Smoking cigarettes or e-cigarettes within 3 months prior to first dose Use of systemic corticosteroid therapy within 30 days prior to first dose Initiation or cessation of antifibrotic therapy or change of antifibrotic dose regimen within 10 weeks prior to first dose Any history of lung transplant Any concomitant pulmonary disease that could interfere with the evaluation of the study drug or interpretation of patient safety or study results HIV infection, seropositive for HBV, seropositive for HCV Uncontrolled hypertension History of significant cardiac disease History of major surgery within 12 weeks prior to first dose 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

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARO-MMP7<br>single or multiple doses of ARO-MMP7 by inhalation of nebulized solution | Drug: ARO-MMP7 Inhalation Solution<br>* ARO-MMP7 by inhalation of nebulized solution<br>|
| Placebo Comparator: Placebo<br>single or multiple doses of placebo by inhalation of nebulized solution | Drug: Placebo<br>* Calculated volume of normal saline (0.9% NaCl) 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) Over Time |  | From first dose of study drug through the end of study (EOS; up to 85 days, or until sputum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Over Time in Forced Expiratory Volume (FEV1) |  | Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later) | 
| Change From Baseline Over Time in Forced Vital Capacity (FVC) |  | Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later) | 
| Change From Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO) |  | Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later) | 
| PK of ARO-MMP7: Maximum Observed Plasma Concentration (Cmax) |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36 | 
| PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to 24 Hours (AUC0-24) |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36 | 
| PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast) |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36 | 
| PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to Infinity (AUCinf) |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36 | 
| PK of ARO-MMP7: Terminal Elimination Half-Life (t1/2) |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36 | 
| PK of ARO-MMP7: Apparent Systemic Clearance (CL/F) |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36 | 
| PK of ARO-MMP7: Apparent Terminal Phase Volume of Distribution (VZ/F) |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36 | 
| PK of ARO-MMP7: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount excreted; Ae) in NHVs |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30 | 
| PK of ARO-MMP7: Percentage of Administered Drug Recovered in Urine Over 0 to 24 Hours in NHVs |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30 | 
| PK of ARO-MMP7: Renal Clearance (CLr) in NHVs |  | single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30 |