Clinical trial NCT05537025: Study of ARO-MMP7 Inhalation Solution in Healthy Subjects and Patients With Idiopathic Pulmonary Fibrosis
Official title: A Phase 1/2a Study Evaluating the Effects of ARO-MMP7 Inhalation Solution in Healthy Subjects and Patients With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-09-13
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time
timeFrame: 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 outcomes:
measure: Change From Baseline Over Time in Forced Expiratory Volume (FEV1)
timeFrame: Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later)
measure: Change From Baseline Over Time in Forced Vital Capacity (FVC)
timeFrame: Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later)
measure: Change From Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO)
timeFrame: Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later)
measure: PK of ARO-MMP7: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to 24 Hours (AUC0-24)
timeFrame: 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
measure: PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: 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
measure: PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to Infinity (AUCinf)
timeFrame: 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
measure: PK of ARO-MMP7: Terminal Elimination Half-Life (t1/2)
timeFrame: 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
measure: PK of ARO-MMP7: Apparent Systemic Clearance (CL/F)
timeFrame: 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
measure: PK of ARO-MMP7: Apparent Terminal Phase Volume of Distribution (VZ/F)
timeFrame: 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
measure: PK of ARO-MMP7: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount excreted; Ae) in NHVs
timeFrame: 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
measure: PK of ARO-MMP7: Percentage of Administered Drug Recovered in Urine Over 0 to 24 Hours in NHVs
timeFrame: 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
measure: PK of ARO-MMP7: Renal Clearance (CLr) in NHVs
timeFrame: 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
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet- University Hosptial of Copenhagen
city: Odense
country: Denmark
facility: Odense University Hospital
city: Ancona
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti
city: Florence
country: Italy
facility: AOUC Azienda Ospedaliero-Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione Irccs Ca'Granda Ospedale Maggiore Policlinico, Milano
city: Milano
country: Italy
facility: Fondazione Irccs Ca'Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: San Giuseppe Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Soeul
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research-Christchurch
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Giromed Institute - Barcelona
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Trust
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
Study officials:
References: