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

Open to people ages 18-75

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 3-agent immunosuppression regimen that includes a steroid, a calcineurin inhibitor (CNI), and 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) <14 days prior to the baseline visit.
11. Currently using an mTOR inhibitor or azathioprine
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 bronchial stents or cryotherapy within 12 months of the Screening Visit