RECRUITING

Study to Evaluate ARINA-1 in the Prevention of Bronchiolitis Obliterans Progression in Participants With Bilateral Lung Transplant

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The goal of this Phase 3 clinical trial is to compare ARINA-1 (a nebulized immunomodulatory agent) plus Standard of Care vs Standard of Care alone. The main question it aims to answer are: * Evaluate the effectiveness of ARINA-1 in preventing bronchiolitis obliterans syndrome (BOS) progression in participants with a bilateral lung transplant * To evaluate the effectiveness of ARINA-1 on improving quality of life decline and preventing or delaying the use of augmented immunosuppression in participants with pre-BOS relative to SOC. Participants will have clinic visits at screening, randomization (day 1) and weeks 4, 12, 18, and 24. After week 24, participants will have clinic visits at weeks 32, 40, and 48. Participants will also have a telehealth visit on day 2 and phone calls to assess adverse events (AEs), serious adverse events (SAEs), and review patient education will occur during weeks 5, 8, 36, and 44.

Official Title

A Phase 3, Open-label, Randomized, Standard of Care-controlled, Parallel Study Arm Study to Demonstrate Efficacy and Safety of ARINA-1 in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) Progression in Participants With a Bilateral Lung Transplant

Quick Facts

Study Start:2023-04-10

Study Completion:2026-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05654922

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Bilateral lung transplant \>12 months from the time of Visit 1 / Randomization 2. Age 18-75 years old at the time of consent 3. Routinely followed at enrolling site 4. Willing and able to comply with visit schedule and at-home requirements 5. 10-24% decrease in FEV1 from the post-transplant baseline within the last 12 months. 6. Capable of giving informed consent 7. On a stable maintenance regimen of azithromycin for \>4 weeks prior to the Screening Visit 8. On a stable 2-agent or 3-agent immunosuppression regimen that includes a steroid, a calcineurin inhibitor (CNI), and, optionally, a cell cycle inhibitor (e.g., mycophenolate, azathioprine) \>4 weeks prior to Screening 9. If a woman of childbearing potential (WOCBP), must agree to use a reliable method of birth control for the entire duration of the study.	1. Positive urine pregnancy test at screening and baseline visit 2. Diagnosis of active congestive heart failure or symptomatic coronary artery disease \> grade 3 based on the New York Heart Association Functional Classification (NYHA) criteria 3. Restrictive allograft syndrome (RAS) defined by radiographic interstitial or alveolar opacities on chest X-ray or CT scan that are consistent with RAS 4. Have advanced BOS, defined by \>24% decrease in FEV1 in post-transplant baseline 5. A diagnosis of probable antibody-mediated rejection (AMR) \<12 months prior to the baseline visit 6. Donor-specific antibodies (DSA) identified \<6 months prior to the baseline visit. \*The presence of DSA \>6 months from the baseline visit is acceptable for enrollment into the study. 7. Unresolved diffuse alveolar damage 8. Receiving mechanical ventilation 9. Chronic kidney disease stage IV or higher, including on dialysis 10. Initiating a new maintenance therapy or changing immunosuppression maintenance therapy (e.g., changing tacrolimus to cyclosporine) \<30 days prior to the baseline visit. 11. Have initiated or changed mTOR maintenance therapy \<3 months prior to Clinic Visit 1 (mTOR use for \>3 months is allowed) 12. Initiating or changing antibiotic (including azithromycin), antiviral, or antifungal therapy \<14 days prior to the baseline visit. 13. Use of alemtuzumab \<6 months prior to the baseline visit 14. Use of anti-thymocyte therapies (e.g., anti-thymocyte globulin) or photopheresis \<90 days prior to the Screening Visit. Prior use of Trikafta (elexacaftor, ivacaftor, and tezacaftor is allowed as long as the participant has been on stable dose for \>90 days prior to the Screening Visit. 15. Initiating a multivitamin or other supplement (inhaled, oral, or IV) containing vitamin C, glutathione, or N-acetylcysteine \<90 days prior to the baseline visit 16. Significant unstable comorbidities, in the opinion of the site investigator 17. Allery or previous adverse reaction to azithromycin 18. A diagnosis of dynamic collapse / tracheobrochomalacia \<90 days of the baseline visit. 19. Subjects currently participating in, or who have participated in an interventional (drug or device) clinical study \<30 days of the baseline visit. 20. Have been diagnosed with ARAD within 6 weeks of the Screening Visit. 21. Have used belatacept \<6 months prior to Clinic Visit 1 22. Have had an initial treatment of bronchial stents or cryotherapy within 12 months of the Screening Visit, or had bronchial stents removed within the last 3 months of the Screening Visit.

Inclusion Criteria

Exclusion Criteria

1. Bilateral lung transplant \>12 months from the time of Visit 1 / Randomization
2. Age 18-75 years old at the time of consent
3. Routinely followed at enrolling site
4. Willing and able to comply with visit schedule and at-home requirements
5. 10-24% decrease in FEV1 from the post-transplant baseline within the last 12 months.
6. Capable of giving informed consent
7. On a stable maintenance regimen of azithromycin for \>4 weeks prior to the Screening Visit
8. On a stable 2-agent or 3-agent immunosuppression regimen that includes a steroid, a calcineurin inhibitor (CNI), and, optionally, a cell cycle inhibitor (e.g., mycophenolate, azathioprine) \>4 weeks prior to Screening
9. If a woman of childbearing potential (WOCBP), must agree to use a reliable method of birth control for the entire duration of the study.

1. Positive urine pregnancy test at screening and baseline visit
2. Diagnosis of active congestive heart failure or symptomatic coronary artery disease \> grade 3 based on the New York Heart Association Functional Classification (NYHA) criteria
3. Restrictive allograft syndrome (RAS) defined by radiographic interstitial or alveolar opacities on chest X-ray or CT scan that are consistent with RAS
4. Have advanced BOS, defined by \>24% decrease in FEV1 in post-transplant baseline
5. A diagnosis of probable antibody-mediated rejection (AMR) \<12 months prior to the baseline visit
6. Donor-specific antibodies (DSA) identified \<6 months prior to the baseline visit. \*The presence of DSA \>6 months from the baseline visit is acceptable for enrollment into the study.
7. Unresolved diffuse alveolar damage
8. Receiving mechanical ventilation
9. Chronic kidney disease stage IV or higher, including on dialysis
10. Initiating a new maintenance therapy or changing immunosuppression maintenance therapy (e.g., changing tacrolimus to cyclosporine) \<30 days prior to the baseline visit.
11. Have initiated or changed mTOR maintenance therapy \<3 months prior to Clinic Visit 1 (mTOR use for \>3 months is allowed)
12. Initiating or changing antibiotic (including azithromycin), antiviral, or antifungal therapy \<14 days prior to the baseline visit.
13. Use of alemtuzumab \<6 months prior to the baseline visit
14. Use of anti-thymocyte therapies (e.g., anti-thymocyte globulin) or photopheresis \<90 days prior to the Screening Visit. Prior use of Trikafta (elexacaftor, ivacaftor, and tezacaftor is allowed as long as the participant has been on stable dose for \>90 days prior to the Screening Visit.
15. Initiating a multivitamin or other supplement (inhaled, oral, or IV) containing vitamin C, glutathione, or N-acetylcysteine \<90 days prior to the baseline visit
16. Significant unstable comorbidities, in the opinion of the site investigator
17. Allery or previous adverse reaction to azithromycin
18. A diagnosis of dynamic collapse / tracheobrochomalacia \<90 days of the baseline visit.
19. Subjects currently participating in, or who have participated in an interventional (drug or device) clinical study \<30 days of the baseline visit.
20. Have been diagnosed with ARAD within 6 weeks of the Screening Visit.
21. Have used belatacept \<6 months prior to Clinic Visit 1
22. Have had an initial treatment of bronchial stents or cryotherapy within 12 months of the Screening Visit, or had bronchial stents removed within the last 3 months of the Screening Visit.

Contacts and Locations

Study Contact

Carolyn Durham, PhD

CONTACT

919-240-7034

info@renovion.com

Will Anderson

CONTACT

919-240-7034

info@renovion.com

Principal Investigator

Ramsey Hachem, MD

PRINCIPAL_INVESTIGATOR

Barnes-Jewish Hospital / Washington University

Study Locations (Sites)

Dignity Health - St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013

United States

University of California Los Angeles School of Medicine

Los Angeles, California, 90095

United States

University of California San Diego Health

San Diego, California, 92103

United States

Advent Health

Orlando, Florida, 32803

United States

University of South Florida

Tampa, Florida, 33606

United States

University of Iowa Hospital

Iowa City, Iowa, 52242

United States

Johns Hopkins Hospital

Baltimore, Maryland, 21287

United States

University of Minnesota Medical School

Minneapolis, Minnesota, 55455

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Columbia University Irving Medical Center

New York, New York, 10032

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43221

United States

Medical University of South Carolina

Charleston, South Carolina, 29452

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 45390

United States

Baylor Scott and White Research Institute

Dallas, Texas, 75246

United States

Houston Methodist Hospital

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Renovion, Inc.

Ramsey Hachem, MD, PRINCIPAL_INVESTIGATOR, Barnes-Jewish Hospital / Washington University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-10

Study Completion Date2026-11

Study Record Updates

Study Start Date2023-04-10

Study Completion Date2026-11

Terms related to this study

Additional Relevant MeSH Terms

Pre-Bronchiolitis Obliterans Syndrome