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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03657342
Other study ID # BT - L-CsA - 301 - SLT
Secondary ID 2018-003204-39
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date April 2, 2019
Est. completion date November 2024

Study information

Verified date October 2023
Source Zambon SpA
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The objective of the trial is to assess efficacy and safety of add-on aerosolized liposomal cyclosporine A (L-CsA) to Standard of Care (SoC) therapy as compared to SoC therapy alone in the treatment of Bronchiolitis obliterans syndrome (BOS) in single lung transplant recipients.


Description:

This is a Phase III randomized, controlled clinical trial of L-CsA for the treatment of bronchiolitis obliterans syndrome in adults diagnosed with BOS following single lung transplant. Patients will receive either L-CsA (5 mg) via the PARI Investigational eFlow® Device twice daily plus Standard of Care (SoC) treatment, or SoC alone, for a period of 48 weeks. All patients will be eligible to continue in an open-label extension trial of L-CsA following completion of BOSTON-1. Regardless of treatment allocation, all patients will continue to receive their SoC regimen for maintenance of the lung allograft. Eligible patients for the clinical trial must have a tacrolimus-based triple-drug therapy in combination with mycophenolate mofetil or its equivalent and a corticosteroid. A total of 11 visits will be performed during the clinical trial. After informed consent has been obtained, a Screening Visit will be carried out in order to check general eligibility for participation. At the Randomization Visit, inclusion and exclusion criteria will be re-checked and spirometry performed. During the 48-week treatment period, visits are scheduled every 4-8 weeks. If a patient has an event that meets one of the criteria for progression of BOS, he/she will return to the clinic at least 2-weeks later for an unscheduled visit to have spirometry and other procedures performed.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 220
Est. completion date November 2024
Est. primary completion date April 5, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Adult patients = 18 years who received a single lung transplant at least 12 months prior to Screening. 2. Patients with BOS diagnosis defined as CLAD-BOS phenotype with: 1. Screening FEV1 between 85-51% of personal best FEV1 value post-transplant OR 2. Screening FEV1 >85% of personal best FEV1 associated with EITHER a = 200 mL decrease in FEV1 in the previous 12 months OR according to medical history showing BOS progression. 3. Diagnosis of CLAD-BOS must be made at least 12 months after lung transplantation and 1. within 12 months prior to the screening visit OR 2. more than 12 months from screening and patient must have shown a decline in FEV1 = 200ml in the previous 12 months before screening, which is not due to acute infection or acute organ rejection. 4. Patients in whom the diagnosis of BOS has been confirmed by the elimination of other possible causes of obstructive or restrictive lung disease (CLAD - RAS phenotype, see Protocol Specific Definitions). 5. 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. 6. 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. Patients must consent to retrieve prespecified data from the historic medical record (e.g., information related to the transplant surgery; spirometry data; medication use). 7. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to randomization and must agree to use one of the methods of contraception listed in Appendix II through their End of Study Visit. 8. Patients have no concomitant diagnoses that are considered fatal within one year (12 months) of Screening. Exclusion Criteria: 1. Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (CLAD - RAS phenotype, see Protocol Specific Definition ), etc. 2. 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. 3. 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. 4. Mechanical ventilation within 12 weeks prior to Randomization. 5. Patients with uncontrolled hypertension. 6. Patient has baseline resting oxygen saturation of < 89% on room air or use of supplemental oxygen at rest. 7. 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 Baseline Visit. 8. Known hypersensitivity to L-CsA or to cyclosporine A. 9. Patients with chronic renal failure, defined as serum creatinine > 2.5 mg/dL at screening, or requiring chronic dialysis. 10. Patients with liver disease and serum bilirubin > 3-fold upper limit of normal range or transaminases > 2.5 upper limit of normal range. 11. 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. 12. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit. 13. Women who are currently breastfeeding. 14. 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. 15. Patients who have received extracorporeal photophoresis (ECP) for treatment of BOS within 1 month prior to Randomization. 16. Patients who are currently participating in an interventional clinical trial. 17. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures. 18. 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
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
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.

Locations

Country Name City State
Belgium Universitair Ziekenhuis Leuven Leuven
France Hôpitaux Universitaires de Strasbourg Strasbourg
Germany Hannover Medical School - MHH Klinik für Pneumologie Hannover
Germany LMU Klinikum Großhadern Munich
Israel Rabin Medical Center Petah tikva
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain Complexo Hospitalario de A Coruna Coruña
Spain Hospital C.H.U.A.C. La Coruña
Spain Hospital Universitario Puerta de Hierro Madrid
Spain Hospital Marques de Valdecilla Santander
Spain Hospital Universitario y Politécnico La Fe Valencia
United Kingdom Royal Papworth Hospital NHS Foundation Trust Cambridge
United Kingdom University Hospital of South Manchester NHS Foundation Trust Manchester
United Kingdom Wythenshawe Hospital - Cardiothoracic Transplant Unit Manchester
United States Johns Hopkins University Hospital Baltimore Maryland
United States University of Maryland Baltimore Maryland
United States Cleveland Clinic Cleveland Ohio
United States Ohio State University Medical Center Columbus Ohio
United States Baylor University Medical Center Dallas Texas
United States University of Texas Southwestern Medical Center Dallas Texas
United States Duke University Medical Center Durham North Carolina
United States University of Florida Medical Center Gainesville Florida
United States Baylor St. Luke's Medical Center Houston Texas
United States Houston Methodist Hospital Houston Texas
United States Indiana University Health Methodist Hospital Indianapolis Indiana
United States Mayo Clinic Jacksonville Jacksonville Florida
United States University of Kentucky Albert B. Chandler Hospital Lexington Kentucky
United States UCLA Medical Center Los Angeles California
United States Columbia University Medical Center New York New York
United States Stanford University Hospital Palo Alto California
United States Temple University Hospital Philadelphia Pennsylvania
United States Banner Health Phoenix Arizona
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States Barnes-Jewish Hospital Saint Louis Missouri
United States UC San Francisco San Francisco California
United States University of South Florida Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Zambon SpA

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Israel,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Adverse Events An AE is an untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine. Baseline through study completion (52 weeks)
Other Acute tolerability of L-CsA change in forced expiratory volume in one second (FEV1); reports of cough or shortness of breath.
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.
Baseline through Week 48
Primary Mean change in FEV1 (mL) from baseline to Week 48 FEV1 is the Forced Expiratory Volume in One Second. Baseline to Week 48
Secondary Mean change in FEV1/FVC from baseline to Week 48 Forced Expiratory Volume in One Second on Forced Vital Capacity. Baseline to Week 48
Secondary Time to Progression of BOS The progression of BOST is defined as the earliest of the following:
Absolute decrease from baseline in FEV1 >/= 10% or >/= 200 mL and absolute decrease in FEV1/FVC of > 5% OR
Change in BOS Severity, OR
Re-transplantation, OR
Death from respiratory failure This endpoint will be assessed in a combined analysis with a similar Phase III clinical trial, BT - L-CsA - 302 - DLT (BOSTON-2) which will be conducted in the same investigational centers in patients who have undergone double-lung transplantations.
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 52 weeks.
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