Aerosol Liposomal Cyclosporine for Chronic Rejection in Lung Transplant Recipients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Rejection of Lung Transplant, Disorder Related to Lung Transplantation, Bronchiolitis Obliterans, Decreased Immunologic Activity

Intervention / Treatment
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* Drug: Liposomal aerosol cyclosporine
* Other: standard immune suppression, oral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic rejection Bronchiolitis obliterans diagnosed by bronchiolitis obliterans syndrome and > 20% decline from the individual patient's best FEV1 is observed Recipient of a double or single lung transplant Receiving immunosuppressive treatment according to institutional standards Exclusion criteria: Active invasive bacterial, viral or fungal infection Current mechanical ventilation Pregnant or breast-feeding woman Known hypersensitivity to cyclosporine A Serum creatinine value of more than 265 μmol/L (3 mg/dL) or chronic dialysis Receipt of an investigational drug as part of a clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liposomal Aerosol Cyclosporine<br>Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant ) | Drug: Liposomal aerosol cyclosporine<br>* inhaled form of immune suppression<br>* Other names: cyclosporine;Other: standard immune suppression, oral<br>* conventional drug Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone and rapamycin<br>* Other names: sirolimus;|
| Active Comparator: Conventional oral immune suppression<br>Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone. Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone rapamycin described in the subsequent section as well. | Other: standard immune suppression, oral<br>* conventional drug Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone and rapamycin<br>* Other names: sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants With Chronic Rejection Who Met Primary Combined End-point | Treatment failure defined as: BOS progression (> 20% decline lung function), re-transplant, or death | approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine Analysis From BAL Fluid in Lung | Multiple cytokines were assessed as markers of lung inflammation that may be used in addition to biopsy data, collected per patient as clinically indicated during the follow-up interval. Values are reported as mean change from baseline in each group, per week | baseline to approximately 1 year | 
| Overall Survival at 5 Years Follow-up | Number of participants surviving at 5 year follow-up | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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case-control study, aerosolized liposomal cyclosporine A, bronchiolitis obliterans syndrome, Lung Transplantation, Lung function