Aerosol Liposomal Cyclosporine for Chronic Rejection in Lung Transplant Recipients

University of Maryland Baltimore (UMB)

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Other: standard immune suppression, oral; Drug: Liposomal aerosol cyclosporine

Study type: Interventional

Funder types: Other

Identifiers

NCT01650545

HP-00049596

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 2 patient groups

Liposomal Aerosol Cyclosporine

Experimental group

Description:

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 )

Treatment:

Drug: Liposomal aerosol cyclosporine

Other: standard immune suppression, oral

Conventional oral immune suppression

Active Comparator group

Description:

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.

Treatment:

Other: standard immune suppression, oral