A Phase III, Prospective, Multicenter, Randomized, Controlled Clinical Trial to Demonstrate the Efficacy and Safety of Liposomal Cyclosporine A (L-CsA) Inhalation Solution Delivered via the PARI Investigational eFlow® Device plus Standard of Care versus Standard of Care Alone in the Treatment of Chronic Lung Allograft Dysfunction / Bronchiolitis Obliterans Syndrome in Patients post Double Lung Transplantation - BOSTON-2

Zambon SpA0 sites170 target enrollmentSeptember 28, 2021

ConditionsChronic Lung Allograft Dysfunction / Bronchiolitis Obliterans Syndromein Patients post Double Lung Transplantation MedDRA version: 20.0Level: LLTClassification code 10049202Term: Bronchiolitis obliteransSystem Organ Class: 100000004855 Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Chronic Lung Allograft Dysfunction / Bronchiolitis Obliterans Syndromein Patients post Double Lung Transplantation
Sponsor: Zambon SpA
Enrollment: 170
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

September 28, 2021

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Zambon SpA

Eligibility Criteria

Inclusion Criteria

•1\. Adult patients of \= 18 years who received a double lung transplant at least 12 months prior to Screening.
•2\. Patients with BOS diagnosis defined as CLAD\-BOS phenotype with:
•a) Screening FEV1 between 85\-51% of personal best FEV1 value post\-transplant.
•b) 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.
•3\. Diagnosis of CLAD\-BOS must be made at least 12 months after lung transplantation and
•a) within 12 months prior to the screening visit.
•b) 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.
•4\. 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).
•5\. Patients should be on a 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 as third agent. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. In case a patient is also receiving concomitant azithromycin for prophylaxis or treatment of BOS, in addition to the previously described immunusuppresive regimen , azythromicin regimen must be on a stable regimen for a least 4\-weeks prior to randomization.
•6\. 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

•1\. Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (CLAD – RAS phenotype, see Protocol Specific Definitions),etc.
•2\. Cystic Fibrosis patients with multi\-drug resistant infections not responding to available anti\-microbial therapies.
•3\. 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.
•4\. Active 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
•5\. Mechanical ventilation (including CPAP) within 12 weeks prior to Randomization.
•6\. Patients with uncontrolled hypertension.
•7\. Patient has baseline resting oxygen saturation of \< 89% on room air or use of supplemental oxygen at rest.
•8\. 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.
•9\. Known hypersensitivity to L\-CsA or cyclosporine A.
•10\. Patients with chronic renal failure defined as serum creatinine \> 2\.5 mg/dL at screening or requiring chronic dialysis.