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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 )	Drug: Liposomal aerosol cyclosporine; inhaled form of immune suppression; Other Names: cyclosporine; Other: standard immune suppression, oral; conventional drug Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone and rapamycin; Other Names: tacrolimus; rapamycin; sirolimus
Active Comparator: Conventional oral immune suppression; 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; conventional drug Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone and rapamycin; Other Names: tacrolimus; rapamycin; sirolimus

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Aldo T Iacono, MD, University of Maryland

Publications and helpful links

General Publications

• Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50. doi: 10.1056/NEJMoa043204.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: June 27, 2012
• First Submitted That Met QC Criteria: July 23, 2012
• First Posted (Estimated): July 26, 2012

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Lung function; case-control study; Lung Transplantation; bronchiolitis obliterans syndrome; aerosolized liposomal cyclosporine A
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis; Bronchiolitis Obliterans; Bronchiolitis Obliterans Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Calcineurin Inhibitors; Tacrolimus; Sirolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: HP-00049596

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO