Study of ARO-RAGE in Healthy Subjects and Patients With Inflammatory Lung Disease
Primary Purpose
Asthma, Cystic Fibrosis
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ARO-RAGE
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma
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 for at least 4 weeks prior to Screening (asthma patients only)
- Non-smoking
- Able to produce an induced sputum sample at Screening
- 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 within 30 days prior to first dose and/or acute upper respiratory infection within 7 days prior to first dose
- Positive COVID-19 test during Screening window
- Chronic or acute infection that is clinically significant or requires treatment with systemic antibiotics, antivirals, antifungals, or antiparasitics within 30 days prior to first dose
- 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 theophylline within 30 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
Sites / Locations
- Institute for Respiratory Health-PerthRecruiting
- Jeonbuk National University HospitalRecruiting
- Hanyang University Seoul HospitalRecruiting
- New Zealand Clinical ResearchRecruiting
- New Zealand Respiratory and Research InstituteRecruiting
- Prywatny Gabinet Internistyczno-AlergologicznyRecruiting
- Krakmed.NZOZRecruiting
- Medicome SP.ZO.ORecruiting
- Giromed Institute BarcelonaRecruiting
- Sriraj HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ARO-RAGE
Placebo
Arm Description
ARO-RAGE Inhalation
(0.9% NaCl)
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Secondary Outcome Measures
Change from Baseline Over Time in Forced Expiratory Volume (FEV1)
Change from Baseline Over Time in Forced Vital Capacity (FVC)
Change from Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO)
PK of ARO-RAGE: Maximum Observed Plasma Concentration (Cmax)
PK of ARO-RAGE: Time to Maximum Observed Plasma Concentration (Tmax)
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to 24 Hours (AUC0-24)
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to the Last Quantifiable Plasma Concentration (AUClast)
PK of ARO-RAGE: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity (AUCinf)
PK of ARO-RAGE: Terminal Elimination Half-Life (t1/2)
PK of ARO-RAGE: Apparent Systemic Clearance (CL/F)
PK of ARO-RAGE: Apparent Terminal-Phase Volume of Distribution (VZ/F)
PK of ARO-RAGE: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae)
PK of ARO-RAGE: Percentage of Administrated Drug Recovered in Urine Over 0 to 24 hours
PK of ARO-RAGE: Renal Clearance (CLr)
Full Information
NCT ID
NCT05276570
First Posted
March 3, 2022
Last Updated
October 17, 2023
Sponsor
Arrowhead Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05276570
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 29, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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, cystic fibrosis [CF]). 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 inflammatory lung disease 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
142 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ARO-RAGE
Arm Type
Experimental
Arm Description
ARO-RAGE Inhalation
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
(0.9% NaCl)
Intervention Type
Drug
Intervention Name(s)
ARO-RAGE
Intervention Description
single or multiple doses of ARO-RAGE by inhalation of nebulized solution
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
calculated volume to match active treatment by inhalation of nebulized solution
Primary Outcome Measure Information:
Title
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)
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
Title
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
Title
PK of ARO-RAGE: Percentage of Administrated Drug Recovered in Urine Over 0 to 24 hours
Time Frame
Through 24 hours post-dose
Title
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 CF participants, and up to 24 hours post-dose for participants with asthma
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Confirmed diagnosis of Cystic Fibrosis based on source verifiable medical record (CF patients only)
No abnormal finding of clinical relevance at Screening (other than asthma for asthma patients and CF for CF 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
Stable regimen of CF therapy for at least 6 weeks prior to Screening (CF patients only)
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/CF 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 or CF in CF 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical Monitor
Phone
626-304-3400
Email
ARORAGE@arrowheadpharma.com
Facility Information:
Facility Name
Institute for Respiratory Health-Perth
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meaghan Shorten
Phone
+61 51 0944
Email
meagan.shorten@resphealth.uwa.edu.au
First Name & Middle Initial & Last Name & Degree
John Blakey, MD
Facility Name
Jeonbuk National University Hospital
City
Jeonju
ZIP/Postal Code
54907
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MiYoung Oh
Phone
+ 82 10 4922 0343
Email
pure53@naver.com
First Name & Middle Initial & Last Name & Degree
Yonchul Lee, MD
Facility Name
Hanyang University Seoul Hospital
City
Seoul
ZIP/Postal Code
04763
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sumi So
Phone
1092610942
Email
ssossum2144@gmail.com
First Name & Middle Initial & Last Name & Degree
Kim
First Name & Middle Initial & Last Name & Degree
Sang Heon Kim, MD
Facility Name
New Zealand Clinical Research
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Taisha Stowers
Phone
+64 937 33479
Email
taisha.stowers@nzcr.co.nz
First Name & Middle Initial & Last Name & Degree
Mark O'Carroll
Facility Name
New Zealand Respiratory and Research Institute
City
Auckland
ZIP/Postal Code
1051
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Gane
Phone
+64 9-638 5255
Email
melissa@nzrsi.health.nz
First Name & Middle Initial & Last Name & Degree
Fay Sommerville
Phone
+64 9-638 5255
Email
fay@nzrsi.health.nz
First Name & Middle Initial & Last Name & Degree
Michelle Baker, MD
Facility Name
Prywatny Gabinet Internistyczno-Alergologiczny
City
Białystok
ZIP/Postal Code
15-010
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grzegorz Siergiejko
Phone
48 60189 6534
Email
siergiejko.grzegorz@gmail.com
First Name & Middle Initial & Last Name & Degree
Zenon Siergiejko, MD
Facility Name
Krakmed.NZOZ
City
Kraków
ZIP/Postal Code
31-455
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aleksandra Hajol-Gora
Phone
48 50829 9646
Email
ola.hajolgora@gmail.com
First Name & Middle Initial & Last Name & Degree
Elzbieta Hajol, MD
Facility Name
Medicome SP.ZO.O
City
Oświęcim
ZIP/Postal Code
32-600
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Olejniczak
Email
aolejniczak@medicome.pl
Phone
48 57090 7205
First Name & Middle Initial & Last Name & Degree
Iwona Kobielsz-Gembala, MD
Facility Name
Giromed Institute Barcelona
City
Barcelona
ZIP/Postal Code
08017
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabet Arboix
Phone
+34972183397
Email
elisabet.arboix@giromedinstitute.com
First Name & Middle Initial & Last Name & Degree
Juan Roldan Sanchez, MD
Facility Name
Sriraj Hospital
City
Bangkok Noi
State/Province
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Walaiporn Wongsrisakunkaew
Phone
6695-512-2590
Email
walaiporn_noon@AROMUCRAGE.onmicrosoft.com
First Name & Middle Initial & Last Name & Degree
Kittipong Maneechotesuwan, MD
12. IPD Sharing Statement
Learn more about this trial
Study of ARO-RAGE in Healthy Subjects and Patients With Inflammatory Lung Disease
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