Bronchiolitis Obliterans Syndrome in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
Conditions
Interventions
Product Name: Liposomal Cyclosporine A
Product Code: L-CsA
Pharmaceutical Form: Powder and solvent for nebuliser solution
INN or Proposed INN: Ciclospor
Sponsors
Breath Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age = 18 years. 2. Patient must have a history of allo-HSCT, regardless of source of stem cell or donor or indication for allo-HSCT 3. Documented diagnosis of cGvHD in any organ other than the lung. If BOS is the only manifestation of cGvHD, lung biopsy must have been performed before entering the trial to confirm BOS diagnosis. 4.Confirmed diagnosis of BOS Score 1 within > 6 months and =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1.Active bacterial, viral (as confirmed by multiplex PCR) or fungal infection not successfully resolved at least 4 weeks prior to the Screening Visit. 2.Chronic renal dysfunction with serum creatinine = 2.5 mg/dL or need for renal dialysis. 3.Chronic hepatic dysfunction with serum total bilirubin > 5x upper limit of normal (ULN), transaminases > 5x ULN, or alkaline phosphatase > 5x ULN. 4. Evidence of relapse of the primary malignancy which warranted allogeneic bone marrow transplant. 5. Use of azithromycin within 4 weeks prior to Randomization (Visit 1). 6. Use of zafirlukast during the study period. 7. Chronic oxygen use or use of non-invasive ventilation. 8. Active smokers (i.e. any kind of inhaled nicotine consumption). 9. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy over the course of the clinical trial (for details see Appendix II). 10. Women who are currently breastfeeding. 11. Known hypersensitivity to L-CsA or to cyclosporine A. 12. Patients who do not tolerate administration of inhaled bronchodilators (e.g., salbutamol). 13. Patients with life-expectancy of less than 6 months. 14. Treatments with other Investigational Medicinal Products (IMPs) or previous therapies within four weeks or five times half-life of the drug, whichever is longer prior to screening and during the study. Participation in registries, considering the before, is allowed. 15. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures. 16. 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. 17. Pre-scheduled hospitalizations, surgeries or interventions planned to be performed after obtaining Informed Consent for this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the tolerability and safety, of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for the treatment of BOS in adult allo-HSCT recipients.;Secondary Objective: The secondary objectives of this study are to assess PK and exploratory efficacy and quality of life of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for the treatment of BOS in adult allo-HSCT recipients.; Primary end point(s): IMP tolerability and safety during the first 4 weeks of treatment IMP Tolerability Parameters: • Local Tolerability: o Cough o Wheezing o Bronchospasm o Throat irritation o Change in FEV1 •Overall Tolerability: o Clinical Global Impressions (CGI) scale o Investigator’s tolerability assessment at Visit 3 Safety Parameters: • Adverse events (AEs) • Serious adverse events (SAEs) • Clinical laboratory values • Vital signs ; Timepoint(s) of evaluation of this end point: IMP tolerability and safety during the first 4 weeks of treatment Please refer to 'Schedule of Activities' in the Protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): IMP tolerability and safety during the first 12 weeks of treatment; IMP Tolerability Parameters: • Local Tolerability: o Cough o Wheezing o Bronchospasm o Throat irritation o Change in FEV1 •Overall Tolerability: o Clinical Global Impressions (CGI) scale o Investigator’s tolerability assessment at Visit 3 Safety Parameters: • Adverse events (AEs) • Serious adverse events (SAEs) • Clinical laboratory values • Vital signs CsA Pharmacokinetic Parameters: o Cmax o tmax o AUC0-4h • Whole blood trough levels ; Timepoint(s) of evaluation of this end point: IMP tolerability and safety during the first 12 weeks of treatment; Pharmacokinetic Parameters: • PK: (Week 0) at pre-dose; directly after end of inhalation; 15, 30, and 45 minutes, and 1, 1.5, 2, and 4 hours after end of inhalation: • Whole blood trough levels (at Weeks 2, 4, 8, and 12) Please refer to 'Schedule of Activities' in the Protocol | — |
Countries
Spain
Contacts
Public ContactChief Medical Officer
Breath Therapeutics Inc.
Outcome results
None listed