Clinical trial NCT05276570: Study of ARO-RAGE in Healthy Subjects and Patients With Inflammatory Lung Disease
Official title: A Phase 1/2a Study Evaluating the Effects of ARO-RAGE Inhalation Solution in Healthy Subjects and Patients With Inflammatory Lung Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Asthma
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-03-11
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ARO-RAGE in normal healthy volunteers (NHVs) and in participants with inflammatory lung disease (asthma). In Part 1 of the study, NHVs will receive a single dose of ARO-RAGE or placebo. In Part 2 of the study, adult participants with asthma will receive 2 doses of ARO-RAGE or placebo. Additional NHVs may be randomized to receive 1 or 2 doses of ARO-RAGE or placebo at Sponsor discretion. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.


Eligibility criteria: Inclusion Criteria:

* Normal pulmonary function tests at Screening (NHVs only)
* Confirmed diagnosis of asthma based on source verifiable medical record (asthma patients only)
* No abnormal finding of clinical relevance at Screening (other than asthma for asthma patients)
* Stable dose of asthma controller medications prior to Screening (asthma patients only)
* If on allergen-specific immunotherapy, participants must be on a stable maintenance dose
* Non-smoking
* Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception. Males must not donate sperm during the study and for at least 12 weeks following the last dose of study drug
* Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria:

* Acute lower respiratory infection or asthma exacerbation within 30 days prior to first dose
* Positive COVID-19 test during Screening window
* Use of immunosuppressive medication within 90 days prior to first dose
* Receipt of any intranasal vaccine within 30 days prior to first dose
* Use of systemic corticosteroid therapy within 90 days prior to first dose
* Clinically significant health concerns (other than asthma in asthma patients)
* Human Immunodeficiency virus (HIV) infection, seropositive for Hepatitis B Virus (HBV), seropositive for Hepatitis C Virus (HCV)
* Uncontrolled hypertension
* 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)
timeFrame: From first dose of study drug through the end of study (EOS; up to 113 days)
Secondary outcomes:
measure: Change from Baseline Over Time in Forced Expiratory Volume (FEV1)
timeFrame: Baseline through EOS (up to 113 days) or until serum soluble receptor for advance glycation end products (sRAGE) is ≥ 70% of baseline value
measure: Change from Baseline Over Time in Forced Vital Capacity (FVC)
timeFrame: Baseline through EOS (up to 113 days) or until serum sRAGE is ≥ 70% of baseline value
measure: Change from Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO)
timeFrame: Baseline through EOS (up to 113 days) or until serum sRAGE is ≥ 70% of baseline value
measure: PK of ARO-RAGE: Maximum Observed Plasma Concentration (Cmax)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Terminal Elimination Half-Life (t1/2)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Apparent Systemic Clearance (CL/F)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Apparent Terminal-Phase Volume of Distribution (VZ/F)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
measure: PK of ARO-RAGE: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-RAGE: Percentage of Administrated Drug Recovered in Urine Over 0 to 24 hours
timeFrame: Through 24 hours post-dose
measure: PK of ARO-RAGE: Renal Clearance (CLr)
timeFrame: single dose phase: up to 48 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 29 for NHVs, and up to 24 hours post-dose for participants with asthma
Other outcomes:
Locations:
city: South Brisbane
country: Australia
facility: Mater Hospital
state: Queensland
city: Nedlands
country: Australia
facility: Institute for Respiratory Health-Perth
state: Western Australia
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Auckland
country: New Zealand
facility: New Zealand Respiratory and Research Institute
city: Auckland
country: New Zealand
facility: Pacific Clinical Research Network (PCRN)
city: Białystok
country: Poland
facility: Prywatny Gabinet Internistyczno-Alergologiczny
city: Kraków
country: Poland
facility: Krakmed.NZOZ
city: Oświęcim
country: Poland
facility: Medicome SP.ZO.O
city: Barcelona
country: Spain
facility: Pectus Respiratory Health
city: Bangkok Noi
country: Thailand
facility: Sriraj Hospital
state: Bangkok
city: Bangkok
country: Thailand
facility: Vajira Hospital
Study officials:
References: