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

Inclusion criteria

• Bilateral lung transplant >12 months from the time of Visit 1 / Randomization
• Age 18-75 years old at the time of consent
• Routinely followed at enrolling site
• Willing and able to comply with visit schedule and at-home requirements
• 10-24% decrease in FEV1 from the post-transplant baseline within the last 12 months.
• Capable of giving informed consent
• On a stable maintenance regimen of azithromycin for >4 weeks prior to the Screening Visit
• 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
• If a woman of childbearing potential (WOCBP), must agree to use a reliable method of birth control for the entire duration of the study.

Exclusion criteria

• Positive urine pregnancy test at screening and baseline visit
• Diagnosis of active congestive heart failure or symptomatic coronary artery disease > grade 3 based on the New York Heart Association Functional Classification (NYHA) criteria
• Restrictive allograft syndrome (RAS) defined by radiographic interstitial or alveolar opacities on chest X-ray or CT scan that are consistent with RAS
• Have advanced BOS, defined by >24% decrease in FEV1 in post-transplant baseline
• A diagnosis of probable antibody-mediated rejection (AMR) <12 months prior to the baseline visit
• 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.
• Unresolved diffuse alveolar damage
• Receiving mechanical ventilation
• Chronic kidney disease stage IV or higher, including on dialysis
• Initiating a new maintenance therapy or changing immunosuppression maintenance therapy (e.g., changing tacrolimus to cyclosporine) <30 days prior to the baseline visit.
• Have initiated or changed mTOR maintenance therapy <3 months prior to Clinic Visit 1 (mTOR use for >3 months is allowed)
• Initiating or changing antibiotic (including azithromycin), antiviral, or antifungal therapy <14 days prior to the baseline visit.
• Use of alemtuzumab <6 months prior to the baseline visit
• 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.
• Initiating a multivitamin or other supplement (inhaled, oral, or IV) containing vitamin C, glutathione, or N-acetylcysteine <90 days prior to the baseline visit
• Significant unstable comorbidities, in the opinion of the site investigator
• Allery or previous adverse reaction to azithromycin
• A diagnosis of dynamic collapse / tracheobrochomalacia <90 days of the baseline visit.
• Subjects currently participating in, or who have participated in an interventional (drug or device) clinical study <30 days of the baseline visit.
• Have been diagnosed with ARAD within 6 weeks of the Screening Visit.
• Have used belatacept <6 months prior to Clinic Visit 1
• 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.