Clinical research study to investigate effectiveness and safety of Liposomal Cyclosporine A (L-CsA) in patients with Bronchiolitis obliterans syndrome after double lung transplantation.
- Conditions
- Bronchiolitis Obliterans Syndrome in Patients post Single Lung TransplantationTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-003205-25-GB
- Lead Sponsor
- BREATH Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 110
1. Adult patients = 18 years who received a double lung transplant at least 12 months prior to Screening.
2. Patients with clinically defined BOS (CLAD - BOS phenotype) with screening FEV1 between 85-60% of personal best FEV1 value post-transplant.
3. 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).
4. Patients with a diagnosis of BOS made at least 1 year after transplant surgery and within 12 months prior to the Screening Visit.
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 for at least 4 weeks prior to randomization with respect to the therapeutic agents.
6. 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. Patients must be receiving or have received post-transplant prophylaxis against Cytomegalovirus (CMV) and Pneumocystis pneumonia as per SoC at the site.
8. 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.
9. 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.
10. Patients have no concomitant diagnoses that are considered fatal within one year (12 months) of Screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1. Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (RAS) (CLAD – RAS phenotype, see Protocol Specific Definition ), etc.
2. Cystic Fibrosis patients with multi-drug resistant infections not responding to available anti-microbial therapies.
3. 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.
4. 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.
5. Mechanical ventilation within 12 weeks prior to Randomization.
6. Patients with uncontrolled hypertension.
7. Patient has baseline resting oxygen saturation of < 89% on room air or use of supplemental oxygen at rest.
8. 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 Randomization Visit.
9. Known hypersensitivity to L-CsA or to cyclosporine A.
10. Patients with chronic renal failure, defined as serum creatinine > 2.5 mg/dL at screening, or requiring chronic dialysis.
11. Patients with liver disease and serum bilirubin > 3-fold upper limit of normal range or transaminases > 2.5 upper limit of normal range.
12. 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.
13. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit.
14. Women who are currently breastfeeding.
15. 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.
16. Patients who have received extracorporeal photophoresis(ECP) for treatment of BOS within 1 month prior toRandomization.
17. Patients who are currently participating in an interventional clinical trial.
18. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
19. 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
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy and safety of add-on aerosolized L-CsA to Standard of Care therapy as compared to SoC therapy alone in the treatment of BOS in single lung transplant recipients.;Secondary Objective: Not applicable;Primary end point(s): Mean change in FEV1 (mL) from baseline.;Timepoint(s) of evaluation of this end point: Week 48
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Mean change in FEV1/FVC from baseline;<br>• Time to Progression of BOS, defined as the earliest of the following:<br>- Absolute decrease from baseline in FEV1 ³=10% or = 200 mL and absolute decrease in FEV1/FVC of > 5%, OR<br>- Change in BOS Severity, OR<br>- Re-transplantation, OR<br>- Death from respiratory failure<br>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.<br>;Timepoint(s) of evaluation of this end point: • Week 48<br>• Time to Progression