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: Ciclosporin (Ciclosporinium)
CAS Number: 59865-13-3
Other
Sponsors
Zambon SpA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. Patients must have undergone hematopoietic stem cell transplantation and have documented diagnosis of chronic Graft versus Host Disease (cGvHD) guided by the NIH consensus criteria. 3. Patients must have been diagnosed with BOS within >6 months and = 3 years at Screening visit. 4. Spirometry test carried out at Screening visit must show: A FEV1 above 51% of predicted AND A = 10% decline in FEV1 (L) within 2 years 5. Patient must be capable of understanding the purposes and risks of the study, has given written informed consent, and agrees to comply with the study requirements. 6. 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 of the protocol through their End of Study Visit. 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 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Other acute or chronic restrictive or obstructive lung diseases, including but not limited to: Patients with clinically active asthma (variable and recurring symptoms of airflow obstruction and bronchial hyper-responsiveness), chronic obstructive pulmonary disease, interstitial lung disease, or cryptogenic organizing pneumonia or other causes of restrictive lung disease such as neuromuscular weakness or diaphragmatic paralysis. 2. Any acute pulmonary bacterial, viral (as confirmed by multiplex PCR) or fungal infection not successfully resolved at least 4 weeks prior to the Screening Visit. 3. Chronic renal dysfunction with serum creatinine = 2.5 mg/dL. 4. Chronic hepatic dysfunction with serum total bilirubin > 5x upper limit of normal (ULN), transaminases > 5x ULN, or alkaline phosphatase > 5x ULN. 5. Evidence of clinical relapse of the primary malignancy, according to investigator's judgement, which warranted allogeneic bone marrow transplant. 6. Use of azithromycin within 4 weeks prior to Randomization (Visit 1). 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. 10. Women who are currently breastfeeding. 11. Known hypersensitivity to L-CsA or to cyclosporine A. 12. Patients with life-expectancy of less than 6 months. 13. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to the Screening Visit. Participation in registries is allowed 14. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures. 15. 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. 16. 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 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 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 and Visit 5 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 and Visit 5 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
France, Germany, Spain
Contacts
Public ContactPaola Castellani
Zambon SpA
Outcome results
None listed