Bronchiolitis obliterans Respiratory Other chronic obstructive pulmonary disease
Conditions
Interventions
Current interventions as of 29/06/2015:
Basic immunosuppression: All participants regardless of treatment allocation will receive Standard of Care basic immunosuppression consisting of
Sponsors
PARI Pharma GmbH (Germany)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current information as of 31/03/2010: The following point has been amended as of the above date: 2. Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration Previous information as of 12/05/2009: 1. Patient's written informed consent obtained prior to any screening procedure 2. Received a single lung, bilateral lung or heart/lung transplantation within four weeks prior to first investigational medical product (IMP) administration 3. Male or female greater than or equal to 18 years of age 4. Capable of self-administration of medications 5. Capable of understanding the purpose and risk of the clinical trial 6. Received within one week prior to first IMP administration the following immunosuppressive agents and dosages for maintenance therapy: 6.1. Tacrolimus approximately 0.1 to 0.2 mg/kg/day adjusted to a target serum level (C0, trough) of 8 to 15 µg/L, and 6.2. Mycophenolate mofetil (MMF) 1 to 3 g/day, and 6.3. Prednisone orally; tapered down within the first 3 months after transplantation 7. Female patients with childbearing potential must have a negative serum pregnancy test within 3 days prior to screening. Both women and men must agree to use a medically acceptable method of contraception throughout the IMP treatment period and for 3 months after IMP discontinuation. 8. Estimated life expectancy greater than 6 months Initial information at time of registration: 1. Signed informed consent provided prior to any screening procedure 2. Male or female, 12 years or older 3. Capable of self-administrating medications 4. Capable of understanding the purpose and risk of the study 5. Received a single lung, bilateral lung or heart/lung transplantation within one week prior to first investigational medicinal product (IMP) administration 6. Received within one week prior to first IMP administration the following immunosuppressive agents and dosages for maintenance therapy: 6.1. Tacrolimus 0.1 to 0.2 mg/kg/day adjusted to target serum level (trough concentrations) of 8 to 15 µg/L 6.2. Mycophenolate mofetil (MMF) 1 to 3 g/day, and 6.3. Prednisone orally 0.5 mg/kg/day initial dosing tapered down to approximately 5 mg/week after 2 to 4 weeks 7. Female patients with child bearing potential must have a negative serum pregnancy test within 3 days prior to screening. Both women and men must agree to use a medically-acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include intra-uterine device (IUD), oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository) 8. Estimated life expectancy greater than 6 months
Exclusion criteria
Exclusion criteria: Current information as of 12/05/2009: 1. Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher 2. Any active invasive bacterial, viral or fungal infection within one week prior to first IMP administration 3. Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria within one week prior to first IMP administration 4. Received any systemic or topical ciclosporin A within one week prior to first IMP administration and/or during the clinical trial 5. Received any systemic or topical rosuvastatin within one week prior to first IMP administration and/or during the clinical trial 6. Current mechanical ventilation 7. Received a lung re-transplantation 8. Pregnant or breast feeding woman 9. Has known hypersensitivity to ciclosporin A 10. Has a serum creatinine value of more than 265 µmol/L (3 mg/dL) or chronic dialysis (haemodialysis) 11. Unlikely to comply with visits, inhalation procedures or spirometric measurements scheduled in the protocol 12. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to first administration of IMP 13. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the clinical trial 14. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures 15. Patient was previously enrolled in the present clinical trial Initial information at time of registration: 1. Any previous episode of acute rejection of grade A2 or higher 2. Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher 3. An active invasive bacterial, viral or fungal infection within one week prior to IMP administration 4. Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria within one week prior to first IMP administration 5. Received any systemic or topical cyclosporin within one week prior to first IMP administration and/or during the clinical trial 6. Received mechanical ventilation 7. Received a lung re-transplantation 8. Pregnant or breast feeding woman 9. Has known hypersensitivity to cyclosporin A 10. Has a serum creatinine value of more than 3 mg/dL 11. Unlikely to comply with visits, inhalation procedures or spirometric measurements scheduled in the protocol 12. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to first administration of IMP 13. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the subject's participation in the study 14. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures 15. Has been previously enroll
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 29/06/2015: BOS-free survival Bronchiolitis obliterans syndrome (BOS) Efficacy of L-CsA in preventing the development of bronchiolitis obliterans when given to lung transplant recipients in addition to Standard of Care systemic immunosuppression. Efficacy failure is the combined endpoint of occurrence of BOS (defined as at least a 20% decline from the initial randomization FEV1 value confirmed by two separate measurements of at least three weeks apart) or re-transplantation or death. BOS stage 1 and higher is considered as BOS for the primary endpoint. BOS-free survival is the time from first IMP intake to either first BOS or re-transplantation or death. Previous primary outcome measures: The primary objective is to establish an IMP dosage with the most favourable risk-benefit ratio for the prevention of BO in LT patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 29/06/2015: 1. Efficacy: Pulmonary function parameter, incidence of BOS, overall survival, Incidence of graft loss 2. Safety: Treatment-emergent adverse events (AEs), incidence of invasive bacterial, viral or fungal infections, clinical laboratory, vital signs, physical examination and L-CsA and tacrolimus trough blood levels Previous secondary outcome measures: The secondary objectives are to compare efficacy and safety data from two different L-CsA doses versus placebo and to evaluate investigational medicinal product (IMP) pharmacokinetic (PK) data in bronchoalveolar lavage (BAL) and in whole blood samples. | — |
Countries
Austria, Belgium, France, Germany, Spain, United Kingdom
Outcome results
None listed