Study of Cyclosporine Inhalation Solution (CIS) in Improving Bronchiolitis Obliterans Syndrome-Free Survival Following Lung Transplantation

Study Overview
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Brief Summary
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A Phase III, multi-center, randomized, controlled study designed to demonstrate the efficacy and safety of Cyclosporine Inhalation Solution (CIS)in improving survival and preventing bronchiolitis obliterans syndrome (BOS) when given prophylactically to lung transplant recipients in addition to their standard immunosuppressive regimen.

Official Title
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A Multi-Center, Randomized, Controlled Study to Demonstrate the Efficacy and Safety of Cyclosporine Inhalation Solution (CIS) in Improving Bronchiolitis Obliterans Syndrome-Free Survival Following Lung Transplantation

Conditions
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Lung Transplant

Intervention / Treatment
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* Drug: Cyclosporine Inhalation Solution (CIS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A recipient of a single or double lung transplant (including heart-lung transplant) Age 18 years or older Able to produce a forced expiratory volume in one second (FEV1) of greater than one liter at randomization Eligible subjects must be enrolled within 70 days after receiving a lung transplant Clinical status sufficiently stable to enable routine post-transplant bronchoscopy with bronchoalveolar lavage (BAL) and chest X-ray (or equivalent i.e., chest computerized tomogram (CT)) prior to screening Exclusion Criteria: Lung re-transplantation Documented allergy to propylene glycol and/or cyclosporine Documented respiratory or anastomotic infections unless on appropriate antimicrobial therapy with evidence of clinical response Women who are pregnant, wishing to become pregnant, or unwilling to use appropriate birth control to avoid becoming pregnant Women who are breastfeeding Clinically significant bronchial stenosis unresponsive to dilation and/or stenting Malignancies diagnosed within one year prior to screening (with the exception of non-melanomatous skin cancers)

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CIS<br>CIS in addition to standard immunosuppressive regimen. | Drug: Cyclosporine Inhalation Solution (CIS)<br>* Cyclosporine (USP) Inhalation Solution; 300mg/4.8 mL in propylene glycol (USP) at a concentration of 62.5 mg/mL; 3 times a week for study duration (up to 3 years)<br>* Other names: Cyclosporine;|
| No Intervention: SOC<br>Standard of care (SOC) therapy for lung transplant recipients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of BOS-free survival. Other causes for the decline should be excluded by bronchoscopy and other diagnostic testing performed at the discretion of the investigator. The diagnosis of BOS will be determined by the Outcomes Committee |  | Assessed when symptoms of syndrome present | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization |  | From study initiation through 2+ years after randomization | 
| All cause mortality |  | From study initiation through 2+ years after randomization | 
| Duration of event-free survival, corresponding to the length of time between date of randomization and either death or the occurrence of serious bacterial and viral infections that start in the lungs (defined by reporting of a SAE) |  | From study initiation through 2+ year after randomzation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung transplant, lung transplant recipient, bronchiolitis obliterans syndrome, bronchiolitis obliterans, single lung transplant, double lung transplant, heart-lung transplant, Aerosol