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

Eligibility 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.