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

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: ARO-MMP7 Inhalation Solution; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, DA-2100
    • Research Site 1
  • Odense, Denmark, DK-5000
    • Research Site 2
• Italy
  • Ancona, Italy, 60126
    • Research Site 1
  • Florence, Italy, 50134
    • Research Site 2
  • Milan, Italy, 20122
    • Research Site 3
  • Milan, Italy, 20122
    • Research Site 4
  • Milan, Italy, 20123
    • Research Site 5
• New Zealand
  • Auckland, New Zealand, 1010
    • Research Site 1
  • Christchurch, New Zealand, 08011
    • Research Site 2
• South Korea
  • Seoul, South Korea, 05505
    • Research Site 2
  • Soeul, South Korea, 21565
    • Research Site 3
  • Ulsan, South Korea, 44033
    • Research Site 1
• Spain
  • Barcelona, Spain, 08017
    • Research Site 1
  • Oviedo, Spain, 33011
    • Research Site 2
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Research Site 3
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Research Site 1
  • Edinburgh, United Kingdom, EH16 4SA
    • Research Site 2
  • Manchester, United Kingdom, M23 9QZ
    • Research Site 4
  • Manchester, United Kingdom, M8 5RB
    • Research Site 3

Participation Criteria

Eligibility Criteria

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

Description

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 or plan to undergo transplant during the course of the study
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-MMP7; single or multiple doses of ARO-MMP7 by inhalation of nebulized solution	Drug: ARO-MMP7 Inhalation Solution; ARO-MMP7 by inhalation of nebulized solution
Placebo Comparator: Placebo; single or multiple doses of placebo by inhalation of nebulized solution	Drug: Placebo; Calculated volume of normal saline (0.9% NaCl) 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) 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	Time Frame
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
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)

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Actual): September 5, 2025
• Study Completion (Actual): September 5, 2025

Study Registration Dates

• First Submitted: September 8, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: AROMMP7-1001; 2023-504964-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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