Ensayos clínicos

Inclusion Criteria:

• Adult patients ≥ 18 years who received a single lung transplant at least 12 months prior to Screening.
• Patients with clinically defined BOS (CLAD - BOS phenotype) with screening FEV1 between 85-60% of personal best FEV1 value post-transplant.
• Patients with an FEV1/FVC ratio of
• Patients in whom the diagnosis of BOS has been confirmed by the elimination of other possible causes of obstructive lung disease.
• Patients with a diagnosis of BOS made at least 1 year after transplant surgery and within 12 months prior to the Screening Visit.
• Patients should be on a three-drug 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. The regimen must be stable for at least 4-weeks prior to Randomization with respect to the therapeutic agents.
• Patients must consent to retrieve prespecified data from the historic medical record (e.g., information related to the transplant surgery; spirometry data; medication use).
• Patients must be receiving or have received post-transplant prophylaxis against Cytomegalovirus (CMV) and Pneumocystis pneumonia as per SoC at the site.
• 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.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to randomization and must agree to use one of the methods of contraception listed in Appendix II of the protocol through their End of Study Visit.
• Patients have no concomitant diagnoses that are considered fatal within one year (12 months) of Screening.

Exclusion Criteria:

• Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (RAS), etc.
• Patients with Cystic Fibrosis.
• Patients with acute antibody-mediated rejection at Screening. In this context, clinically stable patients displaying low and stable levels of donor-specific antibodies (DSA) at the Screening Visit (as judged by the Investigator) 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.
• 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, 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.