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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05537025
• Other study ID #: AROMMP7-1001
• Secondary ID: 2023-504964-41
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 30, 2023
• Est. completion date: March 2025

Study information

• Verified date: April 2024
• Source: Arrowhead Pharmaceuticals
• Contact: Medical Monitor
• Phone: 626-304-3400
• Email: AROMMP7[@]arrowheadpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 97
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• ARO-MMP7 Inhalation Solution
ARO-MMP7 by inhalation of nebulized solution
• Placebo
Calculated volume of normal saline (0.9% NaCl) to match active treatment by inhalation of nebulized solution

Locations

Country	Name	City	State
Denmark	Odense University Hospital	Odense
New Zealand	New Zealand Clinical Research	Auckland
New Zealand	New Zealand Clinical Research-Christchurch	Christchurch
Spain	Giromed Institute - Barcelona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

Denmark,  New Zealand,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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