Aerosol Liposomal Cyclosporine for Chronic Rejection in Lung Transplant Recipients

Phase 1

Completed

• Conditions: Disorder Related to Lung Transplantation; Bronchiolitis Obliterans; Decreased Immunologic Activity; Chronic Rejection of Lung Transplant
• Interventions: Drug: Liposomal aerosol cyclosporine; Other: standard immune suppression, oral

• Registration Number: NCT01650545
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2012-06-27
• Study Start: 2012-07
• Study First Submitted QC: 2012-07-23
• Study First Posted: 2012-07-26
• Primary Completion: 2015-08
• Results First Submitted: 2017-10-24
• Results First Submitted QC: 2017-10-24
• Results First Posted: 2017-10-25
• Status Verified: 2018-03
• Study Completion: 2019-11
• Last Update Submitted: 2023-05-04
• Last Update Posted: 2023-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Liposomal Aerosol Cyclosporine	Liposomal aerosol cyclosporine	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 )
Liposomal Aerosol Cyclosporine	standard immune suppression, oral	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 )
Conventional oral immune suppression	standard immune suppression, oral	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Cytokine Analysis From BAL Fluid in Lung	baseline to approximately 1 year	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
Overall Survival at 5 Years Follow-up	5 years	Number of participants surviving at 5 year follow-up

Trial Locations

Locations (1)

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States