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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
262
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
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
Mean change in FEV1 from Baseline to Week 24
FEV1 is the Forced Expiratory Volume in One Second
Time frame: Baseline to Week 24
Mean change in FEV1 from Baseline to Week 48
FEV1 is the Forced Expiratory Volume in One Second
Time frame: Baseline to Week 48
Mean change in FEV1 from Baseline to End of Study
FEV1 is the Forced Expiratory Volume in One Second
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: Baseline to End of Study, approximately 2 years
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Banner - University Medical Center
Phoenix, Arizona, United States
David Geffen School of Medicine at UCLA
Los Angeles, California, United States
UCSF
San Francisco, California, United States
UCSF Center for Advanced Lung Disease
Stanford, California, United States
University of Florida Dept of Pulmonary Medicine
Gainesville, Florida, United States
Indiana University
Indianapolis, Indiana, United States
UK Albert B. Chandler Hospital
Lexington, Kentucky, United States
University of Maryland
Baltimore, Maryland, United States
Johns Hopkins University Hospital
Baltimore, Maryland, United States
Barnes-Jewish Hospital
St Louis, Missouri, United States
...and 27 more locations