Idiopathic Pulmonary Fibrosis
Conditions
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.
Interventions
DRUGARO-MMP7 Inhalation Solution
ARO-MMP7 by inhalation of nebulized solution
DRUGPlacebo
Calculated volume of normal saline (0.9% NaCl) to match active treatment by inhalation of nebulized solution
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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 coronavirus disease (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Day 1 up to Day 85 | An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. TEAEs were defined as AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of Study (EOS) in Forced Expiratory Volume in One Second (FEV1) | Baseline, EOS (up to Day 85) | FEV1 was measured using Spirometry. |
| Change From Baseline to the EOS in Forced Vital Capacity (FVC) | Baseline, EOS (up to Day 85) | FVC was measured using Spirometry. |
| Change From Baseline to the EOS in Diffusing Capacity for Carbon Monoxide (DLCO) | Baseline, EOS (up to Day 85) | DLCO measures gas diffusion from the alveoli to the blood and is impaired by alveolar filling processes, interstitial lung diseases (ILDs), and emphysema. DLCO was measured in milliliters (mL)/minute (min)/millimeters of mercury (mmHG). |
| SAD Cohorts: Maximum Observed Plasma Concentration (Cmax) of ARO-MMP7 | Pre-dose (Day 1) up to 168 hours post-dose (Day 8) | — |
| MAD Cohorts: Cmax of ARO-MMP7 | Pre-dose up to 6 hours post-dose on Days 1, 15, and 29 | — |
| IPF Cohorts: Cmax of ARO-MMP7 | Pre-dose up to 6 hours post-dose on Days 1, 15, and 29 | — |
| SAD Cohorts: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of ARO-MMP7 | Pre-dose up to 24 hours post-dose (Day 2) | — |
| MAD Cohorts: AUC0-24 of ARO-MMP7 | Pre-dose up to 24 hours post-dose on Days 1, 15, and 29 | — |
| IPF Cohorts: AUC0-24 of ARO-MMP7 | Pre-dose up to 24 hours post-dose on Days 1, 15, and 29 | — |
| SAD Cohorts: Time to Reach Cmax (Tmax) of ARO-MMP7 | Pre-dose (Day 1) up to 168 hours post-dose (Day 8) | — |
| MAD Cohorts: Tmax of ARO-MMP7 | Pre-dose up to 6 hours post-dose on Days 1, 15, and 29 | — |
| IPF Cohorts: Tmax of ARO-MMP7 | Pre-dose up to 6 hours post-dose on Days 1, 15, and 29 | — |
| Urine PK of ARO-MMP7: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae) in NHVs Enrolled in SAD Cohorts | Pre-dose up to 24 hours post-dose on Day 1 | — |
| Urine PK of ARO-MMP7: Percentage of Administered Drug Recovered in Urine Over 0 to 24 Hours (Fraction Excreted; fe) in NHVs Enrolled in SAD Cohorts | Pre-dose up to 24 hours post-dose on Day 1 | — |
| Urine PK of ARO-MMP7: Renal Clearance (CLr) in NHVs Enrolled in SAD Cohorts | Pre-dose up to 24 hours post-dose on Day 1 | — |
Countries
Denmark, Italy, New Zealand, South Korea, Spain, United Kingdom
Participant flow
Pre-assignment details
The study was divided into 3 groups: normal healthy volunteers (NHV) single ascending dose (SAD) cohorts, NHV multiple ascending dose (MAD) cohorts, and idiopathic pulmonary fibrosis (IPF) cohorts. A total of 105 participants were randomized and received treatment. Of the randomized participants, 82 were NHVs and 23 were participants with IPF.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 16 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race White | 8 Participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 6 | 0 / 12 | 0 / 4 | 0 / 5 | 0 / 4 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 9 / 11 | 5 / 6 | 3 / 6 | 5 / 6 | 10 / 10 | 2 / 6 | 10 / 12 | 3 / 4 | 5 / 5 | 3 / 4 | 3 / 6 | 4 / 6 | 4 / 6 | 4 / 6 | 3 / 5 | 5 / 6 |
| serious Total, serious adverse events | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 6 | 0 / 12 | 0 / 4 | 0 / 5 | 0 / 4 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 5 | 2 / 6 |
Outcome results
None listed