Study to Evaluate ARINA-1 in the Prevention of Bronchiolitis Obliterans Progression in Participants With Bilateral Lung Transplant
Pre-Bronchiolitis Obliterans Syndrome
About this trial
This is an interventional treatment trial for Pre-Bronchiolitis Obliterans Syndrome
Eligibility Criteria
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 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 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) <14 days prior to the baseline visit. Currently using an mTOR inhibitor or azathioprine 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 bronchial stents or cryotherapy within 12 months of the Screening Visit
Sites / Locations
- Dignity Health - St. Joseph's Hospital and Medical Center
- University of California Log Angeles School of MedicineRecruiting
- University of California San Diego HealthRecruiting
- Adventist Health
- University of South FloridaRecruiting
- University of Iowa HospitalRecruiting
- Johns Hopkins HospitalRecruiting
- University of Minnesota Medical SchoolRecruiting
- Washington University School of MedicineRecruiting
- Columbia University Irving Medical CenterRecruiting
- Cleveland ClinicRecruiting
- The Ohio State University Wexner Medical CenterRecruiting
- Medical University of South CarolinaRecruiting
- University of Texas Southwestern Medical CenterRecruiting
- Baylor Scott and White Research Institute
- Houston Methodist HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Other
ARINA-1 plus standard of care
Standard of care only
ARINA-1 (88 mg/mL ascorbic acid, ASC; 150 mg/mL reduced glutathione, GSH); fixed dose, 4 mL solution inhaled twice daily via nebulization plus standard 3-therapy immunosuppression regimen and azithromycin
Standard 3-therapy immunosuppression regimen and azithromycin