Trial Outcomes & Findings for Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Single Lung Transplant (BOSTON-1) (NCT NCT03657342)

Last Updated: 2025-10-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

62 participants

Primary outcome timeframe

Week 48 (V9)

Results posted on

2025-10-27

Participant Flow

The study randomized 62 patients globally from 26Mar2019 to 16Apr2024.

Of the 97 patients screened (up to 4 weeks screening period prior to Visit 1), 62 patients were enrolled, randomized, and treated.

Participant milestones

Participant milestones
Measure	L-CsA treatment plus SoC Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Overall Study STARTED	32	30
Overall Study FAS	32	30
Overall Study SAF	32	30
Overall Study PPS	21	19
Overall Study COMPLETED	20	23
Overall Study NOT COMPLETED	12	7

Reasons for withdrawal

Reasons for withdrawal
Measure	L-CsA treatment plus SoC Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Overall Study Adverse Event, including SAE/Death	6	3
Overall Study Withdrawal by Subject	4	4
Overall Study PATIENT WITHDRAWN BY THE SPONSOR DUE TO USE OF CYCLOSPORINE A DURING TRIAL (NOT ALLOWED)	1	0
Overall Study PI WITHDREW PATIENT DUE TO THE HIS/HER UNSTABLE CLINICAL CONDITION	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	L-CsA treatment plus SoC (SAF) n=32 Participants Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone (SAF) n=30 Participants In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.	Total n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Age, Categorical >=65 years	23 Participants n=5 Participants	25 Participants n=7 Participants	48 Participants n=5 Participants
Age, Continuous	66.9 years STANDARD_DEVIATION 7.20 • n=5 Participants	69.3 years STANDARD_DEVIATION 5.28 • n=7 Participants	68.0 years STANDARD_DEVIATION 6.41 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	17 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	29 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	25 Participants n=7 Participants	53 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	20 participants n=7 Participants	41 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Israel	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Germany	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Spain	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48 (V9)

Population: FAS: The FAS is defined as all randomized patients. Patients were analyzed according to the treatment group to which they were randomized. All primary and secondary endpoints were performed using the FAS, unless otherwise specified. n=25 is the number of patients with data available, not the number of patients in the analysis set (N).

Outcome measures

Outcome measures
Measure	L-CsA treatment plus SoC (FAS) n=25 Participants Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone (FAS) n=25 Participants In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Mean Change in FEV1 (L) From Baseline to Week 48	-0.186 liters Standard Error 0.3093	-0.090 liters Standard Error 0.2879

SECONDARY outcome

Timeframe: Week 48

Forced Expiratory Volume in One Second on Forced Vital Capacity. It was analysed in the FAS using a LMM for repeated measurements and COMPACT data, with baseline FEV1/FVC among covariates. In case of death or re- transplantation events, FEV1/FVC was imputed as zero at each nominal day post event. FEV1/FVC is a calculated ratio used to diagnose obstructive and restrictive lung disease. It represents the proportion of a patient's vital capacity that he/she is able to expire in the first second of forced expiration to the full forced vital capacity.

Outcome measures

Outcome measures
Measure	L-CsA treatment plus SoC (FAS) n=25 Participants Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone (FAS) n=25 Participants In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Mean Change in FEV1/FVC From Baseline to Week 48	0.093 ratio Standard Error 0.2353	0.157 ratio Standard Error 0.2433

SECONDARY outcome

Timeframe: 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.

The progression of BOS is defined as the earliest of the following: * Absolute decrease from baseline in FEV1 by at least 10% or 200 mL and a decrease in FEV1/FVC by at least 5% (if a patient had an event that met this criterion for progression of BOS, progression of BOS must have been confirmed by measurements that were taken with COMPACT spirometer at least 2 weeks apart) OR * Worsening of BOS grade, OR * Re-transplantation, OR * Death from respiratory failure. Rules for censoring progression of BOS are set. More than one type of event might correspond to the event of BOS progression (even those occurring on the same date). In case progression of BOS was defined by more than one criterion on different dates, the earliest event date was considered, i.e., the date closer to randomization was used as the progression date.

Outcome measures

Outcome measures
Measure	L-CsA treatment plus SoC (FAS) n=32 Participants Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone (FAS) n=30 Participants In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Time to Progression of Bronchiolitis Obliterans Syndrome (BOS)	NA Weeks Median and confidence interval limits were not achieved due to low number of events.	NA Weeks Median and confidence interval limits were not achieved due to low number of events.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through study completion (week 48)

Population: SAF: The SAF was defined as all randomized patients receiving SoC and/or at least one dose of L-CsA, independently of the treatment allocation at randomization. All safety and tolerability data were summarized and analyzed using the SAF.

An AE is an untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine.

Outcome measures

Outcome measures
Measure	L-CsA treatment plus SoC (FAS) n=32 Participants Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone (FAS) n=30 Participants In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Number of Patients With Adverse Events (AE) No. of patients with any TEAE of Grade 3 severity (severe)	15 Participants	8 Participants
Number of Patients With Adverse Events (AE) No. of patients with any study treatment-related TEAE	11 Participants	NA Participants
Number of Patients With Adverse Events (AE) No. of patients with any serious TEAE	20 Participants	14 Participants
Number of Patients With Adverse Events (AE) No. of patients with any serious treatment-related TEAE	3 Participants	NA Participants
Number of Patients With Adverse Events (AE) No of patients with any AE	32 Participants	25 Participants
Number of Patients With Adverse Events (AE) No. of patients with any TEAE leading to discontinuation of study treatment	8 Participants	2 Participants
Number of Patients With Adverse Events (AE) No. of patients with any TEAE leading to study discontinuation	6 Participants	3 Participants
Number of Patients With Adverse Events (AE) No. of patients with any TEAE leading to death	6 Participants	3 Participants
Number of Patients With Adverse Events (AE) No. of patients with any TEAE of Grade 1 severity (Mild)	22 Participants	22 Participants
Number of Patients With Adverse Events (AE) No. of patients with any TEAE of Grade 2 severity (Moderate)	14 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through study completion Week 48

Acute tolerability of IMP (L-CsA) during initial dosing was determined by measuring spirometry 1 hour and 4 hours after treatment. The FEV1 was measured prior to dosing with L-CsA. A decline of ≥20% associated with symptoms could have warranted IMP discontinuation. Parameters reflecting acute tolerability of IMP were: spirometry, cough, or dyspnea.

Outcome measures

Outcome measures
Measure	L-CsA treatment plus SoC (FAS) n=29 Participants Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone (FAS) In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Acute Tolerability of L-CsA: Change From Pre-dose to 1 hr and 4h Post-dose 4 hr Post-dose	-0.019 Liters Standard Deviation 0.0701	—
Acute Tolerability of L-CsA: Change From Pre-dose to 1 hr and 4h Post-dose 1 hr Post-dose	-0.022 Liters Standard Deviation 0.0663	—

Adverse Events

L-CsA treatment plus SoC (SAF)

Serious events: 20 serious events

Other events: 28 other events

Deaths: 6 deaths

SoC alone (SAF)

Serious events: 14 serious events

Other events: 17 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	L-CsA treatment plus SoC (SAF) n=32 participants at risk Liposomal Cyclosporine A 5 mg twice daily for 48 weeks + Standard of Care Therapy Liposomal Cyclosporine A: 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	SoC alone (SAF) n=30 participants at risk In this control arm only the standard of care is administered. Standard of care is a maintenance regimen of immunosuppressive agents. standard of care: 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.
Infections and infestations COVID-19	21.9% 7/32 • Number of events 9 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)	16.7% 5/30 • Number of events 5 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)
Infections and infestations Bronchitis	9.4% 3/32 • Number of events 3 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)	3.3% 1/30 • Number of events 1 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 4/32 • Number of events 7 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)	13.3% 4/30 • Number of events 4 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)
Respiratory, thoracic and mediastinal disorders Cough	15.6% 5/32 • Number of events 5 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)	6.7% 2/30 • Number of events 2 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	12.5% 4/32 • Number of events 4 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)	0.00% 0/30 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)
General disorders Oedema peripheral	9.4% 3/32 • Number of events 3 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)	3.3% 1/30 • Number of events 1 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)
Vascular disorders Hypertension	6.2% 2/32 • Number of events 2 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)	13.3% 4/30 • Number of events 4 • Permanent assessment throughout the complete clinical trial period, from baseline (Week 0, Day 1, V1) till week 48 (V9)

Additional Information

Enrica Bucchioni, MD, PhD, Global Clinical Development Senior Director

Zambon SpA

Phone: +3902665241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place