Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Double Lung Transplant (BOSTON-2)

NCT03656926 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: BT - L-CsA - 302 - DLT2018-003205-25
• Study Type: interventional
• Target: 169
• Locations: 9 countries
• Sites: 40

Brief Summary

The objective of this trial was 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 double lung transplant (DLT) recipients with chronic lung allograft dysfunction (CLAD)-bronchiolitis obliterans syndrome (BOS).

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  FEV1 is the Forced Expiratory Volume in One Second. The FEV1 data collected from the on-site COMPACTTM spirometer were to be considered primary, while data collected with the In2itiveTM home spirometer were to be used for supportive analyses.

  Week 48

Secondary Outcomes (2)

• Mean Change in FEV1/ Forced Vital Capacity (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)

• Acute Tolerability of L-CsA: FEV1 Change From Pre-dose to 1 Hour and 4 Hours Post-dose

  Pre-dose and 1- and 4-hours post-dose on Visit 1

• Count of Participants With at Least One Adverse Event (AE)

  Baseline through study completion (52 weeks)

Study Arms (2)

L-CsA treatment plus SoC

EXPERIMENTAL

Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy

Drug: Liposomal Cyclosporine A

Standard of Care

ACTIVE COMPARATOR

This 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. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.

Also known as: L-CsA

L-CsA treatment plus SoC

Standard of Care DRUG

Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. 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, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.

Also known as: SoC

Standard of Care

Eligibility Criteria

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

You may qualify if:

• Patients who met the following criteria as stated in the protocol were included in the study:
• Adult patients of \> or = 18 years who received a DLT at least 12 months prior to Screening.
• Patients with BOS diagnosis defined as CLAD-BOS phenotype with:
• screening FEV1 between 51% and 85% of personal best FEV1 value post-transplant OR
• screening FEV1 \> 85% of personal best FEV1 associated with EITHER a \> or = 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 \>or = 200 ml 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 - restrictive allograft syndrome (RAS) phenotype.
• Patients should have been 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 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 have agreed to use one of the methods of contraception listed in Appendix II of the protocol in Appendix 16.1.1 through their 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 (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 (including CPAP) 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.

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (40)

Banner Health

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

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

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27110, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, 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

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Medical University of Vienna

Vienna, Austria

Location

CHU Erasme

Brussels, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

Copenhagen University Hospital

Copenhagen, Denmark

Location

Marie-Lannelongue

Le Plessis-Robinson, 92350, France

Location

CHU Hopital Nord

Marseille, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

Location

Hannover Medical School

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 Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Marques de Valdecilla

Santander, Spain

Location

University Hospital LA Fe

Valencia, Spain

Location

Royal Papworth Hospital

Cambridge, United Kingdom

Location

University of Manchester

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, M.D., PhD, Global Clinical Development Head
• Organization: Zambon S.p.A.

clinicaltrials@zambongroup.com

+39 02 665241

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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 4, 2018
• Study Start: March 26, 2019
• Primary Completion: March 12, 2024
• Study Completion: March 12, 2024
• Last Updated: February 10, 2026
• Results First Posted: July 24, 2025

Record last verified: 2026-02

Locations

IL (1); FR (3); ES (7); GB (2); AU (1); BE (2); US (21); DE (2); DK (1)