Back to resultsL-CsA in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) in Lung Transplant (LT) Patients
Primary Purpose
Bronchiolitis Obliterans
Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Cyclosporine Inhalation Solution
Sponsored by
About this trial
This is an interventional prevention trial for Bronchiolitis Obliterans
Eligibility Criteria
Inclusion Criteria:
- Patient's written informed consent
- Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration.
- Male or female, 18 years of age
- Capable of self-administration of medications
- Capable of understanding the purpose and risk of the clinical trial
Received the following immunosuppressive agents and dosages for maintenance therapy:
- Tacrolimus and
- Mycophenolate mofetil (MMF) 1 to 3 g/day and
- Prednisone or any other steroid therapy; tapered down
- Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration.
- Estimated life expectancy > 6 month
Exclusion Criteria:
- Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher
- Any active invasive bacterial, viral or fungal infection
- Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria
- Received any systemic or topical ciclosporin A within
- Received any systemic or topical Rosuvastatin
- Current mechanical ventilation
- Received a lung re-transplantation
- Pregnant or breast feeding woman
- Has known hypersensitivity to ciclosporin A
- Has a serum creatinine value of more than 265 µmol/L (3 mg/dL)
- Unlikely to comply with visits, inhalation procedures or spirometric measurements
- Receipt of an investigational drug within 4 weeks prior to first administration of IMP
- Any co-existing medical condition that in the investigator's judgement
- Psychiatric disorders or altered mental status
- Patient was previously enrolled in the present clinical trial
Sites / Locations
- PARI Pharma GmbH
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
L-CsA
L-CsA placebo
Arm Description
Twice daily inhalation of 2.5 ml/10 mg L-CsA for 96 weeks
Twice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months)
Outcomes
Primary Outcome Measures
The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo.
BOS stage 1 and higher is considered as BOS for the primary endpoint.
Secondary Outcome Measures
Cumulative mean incidence of BOS 12, 18 and 24 months after first IMP administration
Further secondary objectives are to compare further efficacy and safety data from L-CsA versus placebo. Evaluation of IMP pharmacokinetic (PK) data in whole blood samples and bronchoalveolar lavage (BAL)are included in the outcome measure.
The main safety evaluation is the incidence of treatment-emergent AEs including clinically relevant laboratory parameters and vital signs
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01334892
Brief Title
L-CsA in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) in Lung Transplant (LT) Patients
Official Title
A Phase II, Multicentre, Randomised, Double-blind, Placebo Controlled Clinical Trial to Investigate the Efficacy and Safety of Aerosolised Liposomal Ciclosporin A Versus Aerosolised Placebo in the Prevention of Bronchiolitis Obliterans Syndrome in Lung Transplant Patients
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Terminated
Why Stopped
Interim analysis results revealed substantial increase of patient number, with unfeasible study prolongation.
Study Start Date
December 2009 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pari Pharma GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Immunosuppression is a key intervention in patients with solid organ transplant and is usually achieved by combination therapy with systemic CsA or tacrolimus with azathioprine, mycophenolate mofetil (MMF), or corticoids. However, the outcomes after lung transplantation are poor when compared with those after heart, kidney, or liver transplantation, with a survival rate of only 55% for recipients of lung transplants.
Additional application of aerosolised L-CsA should suppress T-cell activation in the lung tissue and subsequently BOS development. The overall purpose of this phase-II/III study is to obtain efficacy and safety data of L-CsA in the prevention of BOS.
Detailed Description
Preventive therapeutic intervention by L-CsA is primarily aimed to suppress T-lymphocyte suppression and inflammatory responses and secondly to prevent fibrotic effects making it more likely to be effective in early stages of BOS. Early development of BOS, which mostly will not be diagnosed, and acute organ rejections are strongly patho-physiological associated. Prevention of the very early development of chronic rejection by L-CsA post LTX may be the ideal starting point for IMP application.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiolitis Obliterans
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
130 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-CsA
Arm Type
Active Comparator
Arm Description
Twice daily inhalation of 2.5 ml/10 mg L-CsA for 96 weeks
Arm Title
L-CsA placebo
Arm Type
Placebo Comparator
Arm Description
Twice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months)
Intervention Type
Drug
Intervention Name(s)
Cyclosporine Inhalation Solution
Intervention Description
Cyclosporin for inhalation twice daily
Primary Outcome Measure Information:
Title
The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo.
Description
BOS stage 1 and higher is considered as BOS for the primary endpoint.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Cumulative mean incidence of BOS 12, 18 and 24 months after first IMP administration
Description
Further secondary objectives are to compare further efficacy and safety data from L-CsA versus placebo. Evaluation of IMP pharmacokinetic (PK) data in whole blood samples and bronchoalveolar lavage (BAL)are included in the outcome measure.
The main safety evaluation is the incidence of treatment-emergent AEs including clinically relevant laboratory parameters and vital signs
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient's written informed consent
Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration.
Male or female, 18 years of age
Capable of self-administration of medications
Capable of understanding the purpose and risk of the clinical trial
Received the following immunosuppressive agents and dosages for maintenance therapy:
Tacrolimus and
Mycophenolate mofetil (MMF) 1 to 3 g/day and
Prednisone or any other steroid therapy; tapered down
Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration.
Estimated life expectancy > 6 month
Exclusion Criteria:
Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher
Any active invasive bacterial, viral or fungal infection
Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria
Received any systemic or topical ciclosporin A within
Received any systemic or topical Rosuvastatin
Current mechanical ventilation
Received a lung re-transplantation
Pregnant or breast feeding woman
Has known hypersensitivity to ciclosporin A
Has a serum creatinine value of more than 265 µmol/L (3 mg/dL)
Unlikely to comply with visits, inhalation procedures or spirometric measurements
Receipt of an investigational drug within 4 weeks prior to first administration of IMP
Any co-existing medical condition that in the investigator's judgement
Psychiatric disorders or altered mental status
Patient was previously enrolled in the present clinical trial
Facility Information:
Facility Name
PARI Pharma GmbH
City
Graefelfing
ZIP/Postal Code
82166
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
L-CsA in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) in Lung Transplant (LT) Patients
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