Back to resultsExtension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3) (BOSTON-3)
Primary Purpose
Bronchiolitis Obliterans, Obliterative Bronchiolitis, Bronchiolitis Obliterans Syndrome
Status
Enrolling by invitation
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Liposomal Cyclosporine A 5 mg
Liposomal Cyclosporine A 10 mg
Sponsored by
About this trial
This is an interventional treatment trial for Bronchiolitis Obliterans focused on measuring single and double transplant
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
- 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.
- 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:
- Known hypersensitivity to L-CsA or to cyclosporine A.
- Patients who experienced an AE related to study drug that led to permanent study drug discontinuation in BOSTON-1 or BOSTON-2.
- 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.
- 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, 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.
- Patients who are currently participating in an interventional clinical trial, other than BOSTON-1 or BOSTON-2.
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
- 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.
Sites / Locations
- Banner - University Medical Center
- David Geffen School of Medicine at UCLA
- UCSF
- UCSF Center for Advanced Lung Disease
- University of Florida Dept of Pulmonary Medicine
- Indiana University
- UK Albert B. Chandler Hospital
- University of Maryland
- Johns Hopkins University Hospital
- Barnes-Jewish Hospital
- Columbia University Medical Center
- Duke University
- Cleveland Clinic
- OSU Wexner Medical Center
- Temple University Hospital
- University of Pittsburgh Medical Center
- Baylor University Medical Center
- University of Texas Southwestern Medical Center
- Baylor College of Medicine
- Houston Methodist Hospital
- Waehringer Guertel
- Hôpital Erasme
- Universitair Ziekenhuis Leuven
- Copenhagen University Hospital
- Hopital Marie Lannelongue
- CHU Hopital Nord
- Hopitaux Universitaires de Strasbourg
- Hannover Medical School
- LMU Klinikum Groshadern
- Rabin Medical Center
- Complexo Hospitalario de A Coruna
- Hospital Universitari Vall d'Hebron
- Hospital Universitario Puerta de Hierro - Unidad de Trasplante Pulmonar
- Hospital Marques de Valdecilla
- Unidad de Trasplante Pulmonar del Hospital La Fe
- Royal Papworth Hospital NHS Foundation Trust
- University of Manchester
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
L-CsA 5 mg plus Standard of Care
L-CsA 10 mg plus Standard of Care
Arm Description
L-CsA 5 mg twice daily plus Standard of Care for up to 144 weeks for patients post Single Lung Transplant
L-CsA 10 mg twice daily plus Standard of Care for up to 144 weeks for patients post Double Lung Transplant
Outcomes
Primary Outcome Measures
Mean change in FEV1 from Baseline to Week 24
FEV1 is the Forced Expiratory Volume in One Second
Secondary Outcome Measures
Mean change in FEV1 from Baseline to Week 48
FEV1 is the Forced Expiratory Volume in One Second
Mean change in FEV1 from Baseline to End of Study
FEV1 is the Forced Expiratory Volume in One Second
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.
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 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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04039347
Brief Title
Extension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3)
Acronym
BOSTON-3
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
March 12, 2020 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zambon SpA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiolitis Obliterans, Obliterative Bronchiolitis, Bronchiolitis Obliterans Syndrome
Keywords
single and double transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
262 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
L-CsA 5 mg plus Standard of Care
Arm Type
Experimental
Arm Description
L-CsA 5 mg twice daily plus Standard of Care for up to 144 weeks for patients post Single Lung Transplant
Arm Title
L-CsA 10 mg plus Standard of Care
Arm Type
Experimental
Arm Description
L-CsA 10 mg twice daily plus Standard of Care for up to 144 weeks for patients post Double Lung Transplant
Intervention Type
Drug
Intervention Name(s)
Liposomal Cyclosporine A 5 mg
Other Intervention Name(s)
L-CsA
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Liposomal Cyclosporine A 10 mg
Other Intervention Name(s)
L-CsA
Intervention Description
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
Primary Outcome Measure Information:
Title
Mean change in FEV1 from Baseline to Week 24
Description
FEV1 is the Forced Expiratory Volume in One Second
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Mean change in FEV1 from Baseline to Week 48
Description
FEV1 is the Forced Expiratory Volume in One Second
Time Frame
Baseline to Week 48
Title
Mean change in FEV1 from Baseline to End of Study
Description
FEV1 is the Forced Expiratory Volume in One Second
Time Frame
Baseline to end of study, approximately 2 years
Title
Mean change in FEV1/FVC from Baseline to Week 24
Description
FEV1/FVC is the ratio between Forced Expiratory Volume in One Second and Forced Vital Capacity.
Time Frame
Baseline to Week 24
Title
Mean change in FEV1/FVC from Baseline to Week 48
Description
FEV1/FVC is the ratio between Forced Expiratory Volume in One Second and Forced Vital Capacity.
Time Frame
Baseline to Week 48
Title
Time to Progression of BOS
Description
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
Other Pre-specified Outcome Measures:
Title
Adverse events
Description
An untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine.
Time Frame
Baseline through end of study, approximately 2 years
Title
Acute tolerability of L-CsA as measured by change in FEV1 at 1 hour and 4 hours after first inhalation of L-CsA
Description
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.
Time Frame
First treatment with L-CsA
Title
Acute tolerability of L-CsA as measured by number of patients with treatment-related adverse events
Description
Acute tolerability of L-CsA is measured by number of patients with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame
Baseline through end of treatment, approximately 2 years
Title
Number of patients with treatment-related changes in hematology or serum chemistry parameters
Description
Number of patients with treatment-related changes in hematology or serum chemistry parameters assessed by CTCAE v5.0
Time Frame
Baseline through end of study participation, approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
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.
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:
Known hypersensitivity to L-CsA or to cyclosporine A.
Patients who experienced an AE related to study drug that led to permanent study drug discontinuation in BOSTON-1 or BOSTON-2.
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.
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, 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.
Patients who are currently participating in an interventional clinical trial, other than BOSTON-1 or BOSTON-2.
Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paola R Castellani, MD
Organizational Affiliation
Zambon SpA, Chief Medical Officer
Official's Role
Study Director
Facility Information:
Facility Name
Banner - University Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
UCSF Center for Advanced Lung Disease
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Florida Dept of Pulmonary Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
UK Albert B. Chandler Hospital
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40508
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins University Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
OSU Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Waehringer Guertel
City
Vienna
Country
Austria
Facility Name
Hôpital Erasme
City
Brussel
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Universitair Ziekenhuis Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Copenhagen University Hospital
City
Copenhagen
Country
Denmark
Facility Name
Hopital Marie Lannelongue
City
Le Plessis-Robinson
ZIP/Postal Code
92350
Country
France
Facility Name
CHU Hopital Nord
City
Marseille
Country
France
Facility Name
Hopitaux Universitaires de Strasbourg
City
Strasbourg
Country
France
Facility Name
Hannover Medical School
City
Hannover
Country
Germany
Facility Name
LMU Klinikum Groshadern
City
Munich
Country
Germany
Facility Name
Rabin Medical Center
City
Petah tikva
Country
Israel
Facility Name
Complexo Hospitalario de A Coruna
City
A Coruña
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro - Unidad de Trasplante Pulmonar
City
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Marques de Valdecilla
City
Santander
Country
Spain
Facility Name
Unidad de Trasplante Pulmonar del Hospital La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Royal Papworth Hospital NHS Foundation Trust
City
Cambridge
ZIP/Postal Code
CB23 3RE
Country
United Kingdom
Facility Name
University of Manchester
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Extension Trial on Efficacy / Safety of L-CsA + SoC in Treating BOS in Post Single or Double Lung Transplant (BOSTON-3)
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