A Phase III Clinical Trial to Demonstrate Efficacy / Safety of Liposomal Cyclosporine A + Standard of Care (SoC) vs SoC Alone in Treating Chronic Lung Allograft Dysfunction / Bronchiolitis Obliterans in Patients Post Double Lung Transplant

This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.

Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. Patients receiving azithromycin for prophylaxis or treatment of BOS, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.