Aerosol Liposomal Cyclosporine for Chronic Rejection in Lung Transplant Recipients

A Pilot Study to Demonstrate Efficacy and Safety of Aerosol Liposomal Cyclosporine (L-CsA) in the Treatment of Bronchiolitis Obliterans Syndrome After Lung Transplantation

This is a single-center pilot study to investigate the efficacy and safety of aerosolized liposomal cyclosporine A in the treatment of chronic rejection in lung transplant recipients with bronchiolitis obliterans syndrome (BOS).

The primary objective is to evaluate the efficacy of liposomal cyclosporine A in the treatment of chronic rejection. Pulmonary function and changes in BOS grade are the primary end points.

This is a randomized single-center pilot study to investigate the efficacy and safety of aerosolized liposomal cyclosporine A (L-CsA) in the treatment of chronic rejection in lung transplant recipients with Grade 1 or 2 BOS.

The primary endpoints will include:

• Improvement or stabilization of pulmonary function test (FEV1) from baseline
• Stabilization of histology (no deterioration from baseline)
• Safety of the preparation

The secondary endpoints will include:

• Pharmacokinetics and distribution of CsA in blood -
• Change in cytokine levels from BAL specimens.

Inclusion Criteria:

Chronic rejection

1. Bronchiolitis obliterans diagnosed by bronchiolitis obliterans syndrome and > 20% decline from the individual patient's best FEV1 is observed
2. Recipient of a double or single lung transplant
3. Receiving immunosuppressive treatment according to institutional standards

Exclusion criteria:

1. Active invasive bacterial, viral or fungal infection
2. Current mechanical ventilation
3. Pregnant or breast-feeding woman
4. Known hypersensitivity to cyclosporine A
5. Serum creatinine value of more than 265 μmol/L (3 mg/dL) or chronic dialysis
6. Receipt of an investigational drug as part of a clinical trial