Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-2) (BOSTON-2)
Bronchiolitis Obliterans, Chronic Rejection of Lung Transplant, Lung Transplant Rejection
About this trial
This is an interventional treatment trial for Bronchiolitis Obliterans
Eligibility Criteria
Inclusion Criteria:
- Adult patients ≥ 18 years who received a double lung transplant at least 12 months prior to Screening.
Patients with BOS diagnosis defined as CLAD-BOS phenotype with:
- Screening FEV1 between 85-51% of personal best FEV1 value post transplant. OR
- Screening FEV1 >85% of personal best FEV1 associated with EITHER a ≥ 200 mL decrease in FEV1 in the previous 12 months OR according to medical history showing BOS progression.
Diagnosis of CLAD-BOS must be made at least 12 months after lung transplantation and
- within 12 months prior to the screening visit OR
- more than 12 months from screening and patient must have shown a decline in FEV1 ≥ 200ml in the previous 12 months before screening, which is not due to acute infection or acute organ rejection
- Patients in whom the diagnosis of BOS has been confirmed by the elimination of other possible causes of obstructive or restrictive lung disease (CLAD - RAS phenotype, see Protocol Specific Definitions).
Patients should be on a maintenance regimen of immunosuppressive agents including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent.
The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents.
- Patients capable of understanding the purposes and risks of the clinical trial, who have given written informed consent and agree to comply with the clinical trial requirements/visit schedules, and who are capable of aerosol inhalation. Patients must consent to retrieve prespecified data from the historic medical record (e.g., information related to the transplant surgery; spirometry data; medication use).
Exclusion Criteria:
- Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (RAS) (CLAD - RAS phenotype, see Protocol Specific Definition ), etc.
- Cystic Fibrosis patients with multi-drug resistant infections not responding to available anti-microbial therapies.
- Patients with acute antibody-mediated rejection at Screening. In this context, clinically stable patients (as judged by the Investigator) with detectable levels of donor specific antibodies (DSA) at the Screening Visit are eligible for the study.
- Active acute bacterial, viral, or fungal infection not successfully resolved at least 4 weeks prior to the Screening Visit. Patients with chronic infection or colonization who are clinically stable as per judgement of the Investigator are eligible for the study.
- Mechanical ventilation within 12 weeks prior to Randomization.
- Patients with uncontrolled hypertension.
- Patient has baseline resting oxygen saturation of < 89% on room air or use of supplemental oxygen at rest.
- Evidence of functional airway stenosis (e.g., bronchomalacia/tracheomalacia, airway stents, or airways requiring balloon dilatations to maintain patency) with onset after the initial diagnosis of BOS and ongoing at Screening and/or Randomization Visit.
- Known hypersensitivity to L-CsA or to cyclosporine A.
- Patients with chronic renal failure, defined as serum creatinine > 2.5 mg/dL at screening, or requiring chronic dialysis.
- Patients with liver disease and serum bilirubin > 3-fold upper limit of normal range or transaminases > 2.5 upper limit of normal range.
- Patients with active malignancy within the previous 2 years, including post-transplant lymphoproliferative disorder, with the exception of treated, localized basal and squamous cell carcinomas.
- Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit.
- Women who are currently breastfeeding.
- Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to the Screening Visit. This is defined as any treatment that is implemented under an Investigational New Drug (IND) or compassionate use.
- Patients who have received extracorporeal photophoresis (ECP) for treatment of BOS within 1 month prior to Randomization.
- Patients who are currently participating in an interventional clinical trial.
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
- Any co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the patient's participation in the clinical trial.
Sites / Locations
- Banner Health
- UCLA Medical Center
- Stanford University Hospital
- UC San Francisco
- University of Florida Medical Center
- Mayo Clinic Jacksonville
- University of South Florida
- Indiana University
- University of Kentucky Albert B. Chandler Hospital
- University of Maryland
- Johns Hopkins University Hospital
- Barnes Jewish Hospital
- Columbia University Medical Center
- Duke University Medical Center
- Cleveland Clinic
- Ohio State University Medical Center
- Temple University Hospital
- University of Pittsburgh Medical Center
- Baylor University Medical Center
- University of Texas Southwestern Medical Center
- Baylor College of Medicine
- Houston Methodist Hospital
- Waehringer Guertel
- CHU Erasme
- Universitair Ziekenhuis Leuven
- Copenhagen University Hospital
- CHU Hopital Nord
- Marie-Lannelongue
- Hôpitaux Universitaires de Strasbourg
- Hannover Medical School
- LMU Klinikum Großhadern
- Rabin Medical Center
- Hospital Universitari Vall d'Hebron
- Complexo Hospitalario de A Coruna
- Hospital Puerta de Hierro
- Hospital Marques de Valdecilla
- University Hospital LA Fe
- Royal Papworth Hospital
- University of Manchester
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
L-CsA treatment plus SoC
Standard of Care
Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy
This is a maintenance regimen of immunosuppressive agents