Extension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3) (BOSTON-3)

A Phase III, Extension Clinical Trial to Demonstrate Efficacy and Safety of Liposomal Cyclosprine A Via the PARI Investigational eFlow® Device and SoC in Treating Bronchiolitis Obliterans in Patients Post Single or Double Lung Transplant

The objective of the trial is to assess the long-term safety and efficacy of L-CsA plus Standard of Care (SoC) in the treatment of BOS in single (SLT) and double lung transplant (DLT) recipients.

Study Overview

• Status: Terminated
• Conditions: Bronchiolitis Obliterans; Bronchiolitis Obliterans Syndrome; Obliterative Bronchiolitis
• Intervention / Treatment: Drug: Liposomal Cyclosporine A 5 mg; Drug: Liposomal Cyclosporine A 10 mg

Detailed Description

This is a Phase III, multicenter, open-label, extension clinical trial of L-CsA for the treatment of BOS.

Enrollment will be limited to patients who have completed 48 weeks participation in either the BT-L-CsA-301-SLT (BOSTON-1) or BT-L-CsA-302-DLT (BOSTON-2) trial. All patients in this clinical trial will receive L-CsA in addition to SoC, regardless of the randomization arm in prior trials.

IMP will be administered by BID inhalation (morning/evening) using the L-CsA eFlow. Patients who did not receive L-CsA in BOSTON-1 or BOSTON-2 must remain in the clinic for at least 4 hours for observation after the first inhalation. At all subsequent visits, one dose administered via inhalation will be monitored by the clinical trial center personnel. In case patients receiving L-CsA undergo the last visit for BOSTON-1 or BOSTON-2 (Visit 9) on the same day as for Visit 1 for BOSTON-3, they will take the first dose for Boston 3 in the evening of this day. This first dose will not be supervised by the site staff. Nebulization time per inhalation dose is approximately 6-10 minutes for the 5 mg dose and 9-13 minutes for the 10 mg dose. Inhalations will be performed BID approximately 12 hours apart through a mouthpiece by slow and deep respiration using the L-CsA eFlow. A high efficiency particulate air filter is used to prevent environmental contamination during exhalation.

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Waehringer Guertel
• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
• Denmark
  • Copenhagen, Denmark
    • Copenhagen University Hospital
• France
  • Le Plessis-Robinson, France, 92350
    • Hôpital Marie Lannelongue
  • Marseille, France
    • CHU Hopital Nord
  • Strasbourg, France
    • Hôpitaux Universitaires de Strasbourg
• Germany
  • Hanover, Germany
    • Hannover Medical School
  • Munich, Germany
    • LMU Klinikum Groshadern
• Israel
  • Petah Tikva, Israel
    • Rabin Medical Center
• Spain
  • A Coruña, Spain
    • Complexo Hospitalario de A Coruna
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro - Unidad de Trasplante Pulmonar
  • Santander, Spain
    • Hospital Marques de Valdecilla
  • Valencia, Spain, 46026
    • Unidad de Trasplante Pulmonar del Hospital La Fe
• United Kingdom
  • Cambridge, United Kingdom, CB23 3RE
    • Royal Papworth Hospital NHS Foundation Trust
  • Manchester, United Kingdom
    • University of Manchester
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner - University Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • San Francisco, California, United States, 94143
      • UCSF
    • Stanford, California, United States, 94305
      • UCSF Center for Advanced Lung Disease
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Dept of Pulmonary Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • UK Albert B. Chandler Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • OSU Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients who have completed all visits through the End of Treatment Visit in either BOSTON-1 or BOSTON-2, did not withdraw informed consent, and did not prematurely terminate study drug administration.
2. Patients should be on a three-drug maintenance regimen of immunosuppressive agents including tacrolimus or another CNI, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone.
3. 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.
4. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to Visit 1 and must agree to use one of the methods of contraception listed in Appendix II through their End of Study Visit.

Exclusion Criteria:

1. Known hypersensitivity to L-CsA or to cyclosporine A.
2. Patients who experienced an AE related to study drug that led to permanent study drug discontinuation in BOSTON-1 or BOSTON-2.
3. Patients with new onset of malignancy while participating in BOSTON-1 or BOSTON-2, including post-transplant lymphoproliferative disorder, with the exception of treated, localized basal and squamous cell carcinomas.
4. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit.
5. Women who are currently breastfeeding.
6. Receipt of an investigational drug, other than L-CsA, as part of a clinical trial within 4 weeks prior to Visit 1. This is defined as any treatment that is implemented under an Investigational New Drug (IND) or compassionate use.
7. Patients who are currently participating in an interventional clinical trial, other than BOSTON-1 or BOSTON-2.
8. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
9. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-CsA 5 mg plus Standard of Care; L-CsA 5 mg twice daily plus Standard of Care for up to 144 weeks for patients post Single Lung Transplant	Drug: Liposomal Cyclosporine A 5 mg; 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; Other Names: L-CsA
Experimental: L-CsA 10 mg plus Standard of Care; L-CsA 10 mg twice daily plus Standard of Care for up to 144 weeks for patients post Double Lung Transplant	Drug: Liposomal Cyclosporine A 10 mg; 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; Other Names: L-CsA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in FEV1 from Baseline to Week 24	FEV1 is the Forced Expiratory Volume in One Second	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in FEV1 from Baseline to Week 48	FEV1 is the Forced Expiratory Volume in One Second	Baseline to Week 48
Mean change in FEV1 from Baseline to End of Study	FEV1 is the Forced Expiratory Volume in One Second	Baseline to end of study, approximately 2 years
Mean change in FEV1/FVC from Baseline to Week 24	FEV1/FVC is the ratio between Forced Expiratory Volume in One Second and Forced Vital Capacity.	Baseline to Week 24
Mean change in FEV1/FVC from Baseline to Week 48	FEV1/FVC is the ratio between Forced Expiratory Volume in One Second and Forced Vital Capacity.	Baseline to Week 48
Time to Progression of BOS	The Progression of BOS is defined as the earliest of: Absolute decrease from baseline in FEV1 >/= 10% or >/= 200 mL and absolute decrease in FEV1/FVC of > 5%, OR; Change in BOS severity (according to criteria in Verleden 2019), OR; Re-transplantation, OR; Death from respiratory failure	Baseline to End of Study, approximately 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	An untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine.	Baseline through end of study, approximately 2 years
Acute tolerability of L-CsA as measured by change in FEV1 at 1 hour and 4 hours after first inhalation of L-CsA	Parameters reflecting acute tolerability of IMP are: spirometry, before and 1 hour and 4 hours after inhalation of L-CsA at initial dosing.; cough, or; dyspnea.	First treatment with L-CsA
Acute tolerability of L-CsA as measured by number of patients with treatment-related adverse events	Acute tolerability of L-CsA is measured by number of patients with treatment-related adverse events as assessed by CTCAE v5.0	Baseline through end of treatment, approximately 2 years
Number of patients with treatment-related changes in hematology or serum chemistry parameters	Number of patients with treatment-related changes in hematology or serum chemistry parameters assessed by CTCAE v5.0	Baseline through end of study participation, approximately 2 years

Collaborators and Investigators

• Sponsor: Zambon SpA
• Investigators: Study Director: Paola R Castellani, MD, Zambon SpA, Chief Medical Officer

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2020
• Primary Completion (Actual): February 25, 2026
• Study Completion (Actual): February 25, 2026

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: single and double transplant
• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis; Bronchitis; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Bronchiolitis Obliterans; Anti-Infective Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Dermatologic Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: BT - L-CsA - 303 - FU; 2019-002987-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No