Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-1)

NCT03657342 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: BT - L-CsA - 301 - SLT2018-003204-39
• Study Type: interventional
• Target: 62
• Locations: 7 countries
• Sites: 39

Brief Summary

The objective of this trial is to assess the efficacy and safety of aerosolized liposomal cyclosporine A (L-CsA) as add-on therapy to standard of care (SoC) as compared to SoC alone in single lung transplant recipients with chronic lung allograft dysfunction (CLAD)-bronchiolitis obliterans syndrome (BOS).

Conditions

Bronchiolitis Obliterans; Chronic Rejection of Lung Transplant; Lung Transplant Rejection; Lung Transplant; Complications; Lung Transplant Failure and Rejection; Chronic Lung Allograft Dysfunction

Outcome Measures

Primary Outcomes (1)

• Mean Change in FEV1 (L) From Baseline to Week 48

  FEV1 is the Forced Expiratory Volume in One Second. For FEV1 were considered primary the data collected from the on site COMPACT study spirometer. Baseline is the mean of the best FEV1 obtained with the study spirometer at Screening Visit and the pre-randomization best FEV1 obtained at the Baseline Visit (V1).The primary efficacy analysis was carried out using a Linear Mixed Model (LMM) for repeated measures, using all observed available FEV1 measurements. In case of death or re-transplantation events, FEV1 was imputed as zero at each nominal day post event. PS: Estimates are from a LMM on the response variable with factors for time splines, treatment, the interactions of time splines by treatment, baseline FEV1, the interactions of time splines with baseline FEV1, region, underlying indication for lung transplant (COPD vs all others), use of azithromycin at randomization, and time as random effect.

  Week 48 (V9)

Secondary Outcomes (2)

• Mean Change in FEV1/FVC From Baseline to Week 48

  Week 48

• Time to Progression of Bronchiolitis Obliterans Syndrome (BOS)

  From date of randomization until the date of first documented progression of BOS, or date of retransplantation, or date of death from respiratory failure, whichever came first, assessed up to 48 weeks.

Other Outcomes (2)

• Number of Patients With Adverse Events (AE)

  Baseline through study completion (week 48)

• Acute Tolerability of L-CsA: Change From Pre-dose to 1 hr and 4h Post-dose

  Baseline through study completion Week 48

Study Arms (2)

L-CsA treatment plus SoC

EXPERIMENTAL

Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy

Drug: Liposomal Cyclosporine A

Control treatment

ACTIVE COMPARATOR

In this arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents.

Drug: standard of care

Interventions

Liposomal Cyclosporine A DRUG

This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm

Also known as: L-CsA

L-CsA treatment plus SoC

standard of care DRUG

Standard of Care Therapy. Eligible 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 receiving azithromycin for prophylaxis or treatment of BOS, must be on a stable regimen for a least 4-weeks prior to randomization and will continue to receive azithromycin during the trial as deemed appropriate by the investigator.

Also known as: SoC

Control treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥ 18 years who received a single 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 have been 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 was not due to acute infection or acute organ rejection.
• Patients in whom the diagnosis of BOS had been confirmed by the elimination of other possible causes of obstructive or restrictive lung disease (CLAD - RAS phenotype, see Protocol Specific Definitions).
• Patients should have been on a maintenance regimen of immunosuppressive agents including tacrolimus, a second agent such as but not limited to mycophenolate mofetil (MMF) or azathioprine, and a systemic corticosteroid such as prednisone as third agent. The regimen must have been stable within 4 weeks prior to randomization with respect to the therapeutic agents. In case a patient was also receiving concomitant azithromycin for prophylaxis or treatment of BOS in addition to the previously described immunosuppressive regimen, azithromycin must have been on a stable regimen for at least 4 weeks prior to randomization.
• Patients capable of understanding the purposes and risks of the clinical trial, who had given written informed consent and agreed to comply with the clinical trial requirements/visit schedules, and who were capable of aerosol inhalation. Patients must have consented to retrieve prespecified data from the historic medical record (e.g., information related to the transplant surgery; spirometry data; medication use).
• Women of childbearing potential must have had 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 (EoS) Visit.
• Patients had no concomitant diagnoses that were considered fatal within one year (12 months) of Screening.

You may not qualify if:

• 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 Definition ), etc.
• 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 were 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 were clinically stable as per judgement of the Investigator are eligible for the study.
• Mechanical ventilation (including CPAP) within 12 weeks prior to Randomization.
• Patients with uncontrolled hypertension.
• Patient had 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 Baseline 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 were unwilling to use appropriate birth control to avoid pregnancy through their End of Study (EoS) Visit.
• Women who were currently breastfeeding.
• Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to the Screening Visit. This was defined as any treatment that was implemented under an Investigational New Drug (IND) or compassionate use.
• Patients who had received extracorporeal photophoresis (ECP) for treatment of BOS within 1 month prior to Randomization.

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (39)

Banner Health

Phoenix, Arizona, 85013, United States

Location

Norton Thoracic Institute at St. Joseph's Hospital

Phoenix, Arizona, 85013, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford University Hospital

Palo Alto, California, 94305, United States

Location

UC San Francisco

San Francisco, California, 94143, United States

Location

University of Florida Medical Center

Gainesville, Florida, 32608, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Albert B. Chandler Hospital

Lexington, Kentucky, 40508, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University Hospital

Baltimore, Maryland, 21287, United States

Location

110

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

113

New York, New York, 22042, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

119

Columbus, Ohio, 43210, United States

Location

108

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

Location

Hannover Medical School - MHH Klinik für Pneumologie

Hanover, Germany

Location

LMU Klinikum Großhadern

Munich, Germany

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Complexo Hospitalario de A Coruna

A Coruña, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Marques de Valdecilla

Santander, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Royal Papworth Hospital NHS Foundation Trust

Cambridge, United Kingdom

Location

University Hospital of South Manchester NHS Foundation Trust

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans; Rejection, Psychology

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Enrica Bucchioni, MD, PhD, Global Clinical Development Senior Director
• Organization: Zambon SpA

clinicaltrials@zambongroup.com

+3902665241

Study Officials

• Paola Castellani, MD

  Zambon SpA, Chief Medical Officer and R&D

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This was an open-label clinical trial. Clinical trial monitors, treating physicians, study nurses, study coordinators, and enrolled patients were not blinded to treatment assignment. However, the pulmonary function technicians, respiratory therapists, or physiotherapists who conducted spirometry on-site were blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 5, 2018
• Study Start: March 26, 2019
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: October 27, 2025
• Results First Posted: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); ES (7); DE (2); IL (1); GB (2); US (25); FR (1)