A Clinical Trial to Demonstrate the Effectiveness and Safety of Liposomal Cyclosporine A Inhalation Solution in the Treatment of Bronchiolitis Obliterans Syndrome in Patients Post Double Lung Transplant
This is a Phase III randomized, controlled clinical trial of L-CsA for the treatment of bronchiolitis obliterans syndrome in adults diagnosed with BOS following double lung transplant. Patients will receive either L-CsA (10 mg) via the PARI Investigational eFlow® Device twice daily plus Standard of Care (SoC) treatment, or SoC alone, for a period of 48 weeks. All patients will be eligible to continue in an open-label extension trial of L-CsA following completion of BOSTON-2.
- Bronchiolitis Obliterans
- Chronic Rejection of Lung Transplant
- Lung Transplant Rejection
- Lung Transplant; Complications
- Lung Transplant Failure and Rejection
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Adult patients ≥ 18 years who received a double 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 </= 0.7.
- 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.
- Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (RAS), 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 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.
- 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 ag 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.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Single (Outcomes Assessor)
L-CsA treatment plus SoC
|L-CsA 10 mg twice daily for 48 weeks, plus Standard of Care Therapy||
Standard of Care alone
|Standard of Care Therapy||
UK Center for Clinical and Translational Science and nearby locations
- NCT ID
- Breath Therapeutics Inc.
Study ContactStefanie Prante Fernandes, MSc
+49 (0)159 01803729
Regardless of treatment allocation, all patients will continue to receive their SoC regimen for maintenance of the lung allograft. Eligible patients for the clinical trial must have a tacrolimus-based triple-drug therapy in combination with mycophenolate mofetil or its equivalent and a corticosteroid.
A total of 11 visits will be performed during the clinical trial. After informed consent has been obtained, a Screening Visit will be carried out in order to check general eligibility for participation. At the Randomization Visit, inclusion and exclusion criteria will be re-checked and spirometry performed. During the 48-week treatment period, visits are scheduled every 4-8 weeks. If a patient has an event that meets one of the criteria for progression of BOS, he/she will return to the clinic within 2-weeks for an unscheduled visit to have spirometry and other procedures performed.