AsthmaPhase 1/2NCT05276570
Study of ARO-RAGE in Healthy Subjects and Patients With Inflammatory Lung Disease
A Phase 1/2 study testing ARO-RAGE in people with Asthma, run by Arrowhead Pharmaceuticals at 8 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- ARO-RAGE
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 127 participants
- Where
- 8 sitesin 5 countries
- Study dates
- 29 Jun 2022to 16 Apr 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
New Zealand3 sites
Research Site 1
Auckland, 1010
Research Site 2
Auckland, 1051
Research Site 3
Auckland, 622
About this study
Official title: A Phase 1/2a Study Evaluating the Effects of ARO-RAGE Inhalation Solution in Healthy Subjects and Patients With Inflammatory Lung Disease
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.
- Conditions
- Asthma
- Being tested
- ARO-RAGE, Placebo
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARO-RAGEDrug
single or multiple doses of ARO-RAGE by inhalation of nebulized solution
PlaceboDrug
calculated volume to match active treatment by inhalation of nebulized solution
| Study group | Role | What they receive |
|---|---|---|
| ARO-RAGE | Experimental | ARO-RAGE Inhalation Receives: Drug: ARO-RAGE |
| Placebo | Placebo comparator | (0.9% NaCl) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Measured: From first dose of study drug through the end of study (EOS; up to 113 days)
Secondary outcomes (14)
Change from Baseline Over Time in Forced Expiratory Volume (FEV1)
Measured: Baseline through EOS (up to 113 days) or until serum soluble receptor for advance glycation end products (sRAGE) is ≥ 70% of baseline value
Change from Baseline Over Time in Forced Vital Capacity (FVC)
Measured: Baseline through EOS (up to 113 days) or until serum sRAGE is ≥ 70% of baseline value
Change from Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO)
Measured: Baseline through EOS (up to 113 days) or until serum sRAGE is ≥ 70% of baseline value
PK of ARO-RAGE: Maximum Observed Plasma Concentration (Cmax)
Measured: 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
PK of ARO-RAGE: Time to Maximum Observed Plasma Concentration (Tmax)
Measured: 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
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24)
Measured: 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
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
Measured: 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
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf)
Measured: 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
PK of ARO-RAGE: Terminal Elimination Half-Life (t1/2)
Measured: 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
PK of ARO-RAGE: Apparent Systemic Clearance (CL/F)
Measured: 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
PK of ARO-RAGE: Apparent Terminal-Phase Volume of Distribution (VZ/F)
Measured: 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
PK of ARO-RAGE: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae)
Measured: Through 24 hours post-dose
PK of ARO-RAGE: Percentage of Administrated Drug Recovered in Urine Over 0 to 24 hours
Measured: Through 24 hours post-dose
PK of ARO-RAGE: Renal Clearance (CLr)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2022
- Study start29 Jun 2022
- Primary completion16 Apr 2025
- Study completion16 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arrowhead Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05276570
- Sponsor's protocol ID
- ARORAGE-1001
- Status last verified
- Apr 2026
- First submitted
- 3 Mar 2022
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
O'Carroll M, Kasahara D, Huetsch J, Reed T, Perkins TN, Zhou R, Moser L, Tomasini-Johansson B, Ta A, Oury TD, Pei T, Hamilton J, Bush EW, Leeper NJ, Salathe M; RAGE study consortium. Inhaled siRNA therapy targeting RAGE for pulmonary inflammation: a first-in-human randomized trial. Nat Med. 2026 Sep 9. doi: 10.1038/s41591-026-04607-z. Online ahead of print.
PubMed 42717034
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Study Evaluating the Effects of ARO-RAGE Inhalation Solution in Healthy Subjects and Patients With Inflammatory Lung Disease
- ClinicalTrials.gov ID
- NCT05276570
- Acronym / sponsor ID
- ARORAGE-1001
- Conditions
- Asthma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Arrowhead PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2022 (actual)
- Primary completion
- 16 Apr 2025 (actual)
- Study completion
- 16 Apr 2025 (actual)
- First posted
- 11 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARO-RAGE | Experimental | Drug: ARO-RAGEARO-RAGE Inhalation |
| Placebo | Placebo comparator | Drug: Placebo(0.9% NaCl) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARO-RAGEsingle or multiple doses of ARO-RAGE by inhalation of nebulized solution | Drug | ARO-RAGE |
| Placebocalculated volume to match active treatment by inhalation of nebulized solution | Drug | Placebo |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug through the end of study (EOS; up to 113 days)
14 secondary outcomes
Change from Baseline Over Time in Forced Expiratory Volume (FEV1)
Time frame: Baseline through EOS (up to 113 days) or until serum soluble receptor for advance glycation end products (sRAGE) is ≥ 70% of baseline value
Change from Baseline Over Time in Forced Vital Capacity (FVC)
Time frame: Baseline through EOS (up to 113 days) or until serum sRAGE is ≥ 70% of baseline value
Change from Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO)
Time frame: Baseline through EOS (up to 113 days) or until serum sRAGE is ≥ 70% of baseline value
PK of ARO-RAGE: Maximum Observed Plasma Concentration (Cmax)
Time frame: 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
PK of ARO-RAGE: Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: 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
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24)
Time frame: 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
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
Time frame: 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
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf)
Time frame: 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
PK of ARO-RAGE: Terminal Elimination Half-Life (t1/2)
Time frame: 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
PK of ARO-RAGE: Apparent Systemic Clearance (CL/F)
Time frame: 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
PK of ARO-RAGE: Apparent Terminal-Phase Volume of Distribution (VZ/F)
Time frame: 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
PK of ARO-RAGE: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae)
Time frame: Through 24 hours post-dose
PK of ARO-RAGE: Percentage of Administrated Drug Recovered in Urine Over 0 to 24 hours
Time frame: Through 24 hours post-dose
PK of ARO-RAGE: Renal Clearance (CLr)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Derived from this study: PubMed 42717034O'Carroll M, Kasahara D, Huetsch J, Reed T, Perkins TN, Zhou R, Moser L, Tomasini-Johansson B, Ta A, Oury TD, Pei T, Hamilton J, Bush EW, Leeper NJ, Salathe M; RAGE study consortium. Inhaled siRNA therapy targeting RAGE for pulmonary inflammation: a first-in-human randomized trial. Nat Med. 2026 Sep 9. doi: 10.1038/s41591-026-04607-z. Online ahead of print.
Related trials for Asthma
RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ARO-RAGE in people with Asthma, run by Arrowhead Pharmaceuticals at 8 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in New Zealand, Poland, Australia, Spain, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: From first dose of study drug through the end of study (EOS; up to 113 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05276570, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.