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L-CsA in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) in Lung Transplant (LT) Patients

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ClinicalTrials.gov Identifier: NCT01334892
Recruitment Status : Terminated (Interim analysis results revealed substantial increase of patient number, with unfeasible study prolongation.)
First Posted : April 13, 2011
Last Update Posted : April 14, 2015
Sponsor:
Information provided by (Responsible Party):
Pari Pharma GmbH

Tracking Information
First Submitted Date  ICMJE April 11, 2011
First Posted Date  ICMJE April 13, 2011
Last Update Posted Date April 14, 2015
Study Start Date  ICMJE December 2009
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2011)
The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo. [ Time Frame: 2 years ]
BOS stage 1 and higher is considered as BOS for the primary endpoint.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2011)
Cumulative mean incidence of BOS 12, 18 and 24 months after first IMP administration [ Time Frame: 2 years ]
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE L-CsA in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) in Lung Transplant (LT) Patients
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Bronchiolitis Obliterans
Intervention  ICMJE Drug: Cyclosporine Inhalation Solution
Cyclosporin for inhalation twice daily
Study Arms  ICMJE
  • Active Comparator: L-CsA
    Twice daily inhalation of 2.5 ml/10 mg L-CsA for 96 weeks
    Intervention: Drug: Cyclosporine Inhalation Solution
  • Placebo Comparator: L-CsA placebo
    Twice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months)
    Intervention: Drug: Cyclosporine Inhalation Solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 3, 2013)
130
Original Estimated Enrollment  ICMJE
 (submitted: April 12, 2011)
180
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient's written informed consent
  2. Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration.
  3. Male or female, 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 the following immunosuppressive agents and dosages for maintenance therapy:

    1. Tacrolimus and
    2. Mycophenolate mofetil (MMF) 1 to 3 g/day and
    3. Prednisone or any other steroid therapy; tapered down
  7. Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration.
  8. Estimated life expectancy > 6 month

Exclusion Criteria:

  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
  3. Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria
  4. Received any systemic or topical ciclosporin A within
  5. Received any systemic or topical Rosuvastatin
  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)
  11. Unlikely to comply with visits, inhalation procedures or spirometric measurements
  12. Receipt of an investigational drug within 4 weeks prior to first administration of IMP
  13. Any co-existing medical condition that in the investigator's judgement
  14. Psychiatric disorders or altered mental status
  15. Patient was previously enrolled in the present clinical trial
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01334892
Other Study ID Numbers  ICMJE 12011.201
2008-003800-73 ( EudraCT Number )
ISRCTN66069132 ( Registry Identifier: ISRCTN66069132 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pari Pharma GmbH
Study Sponsor  ICMJE Pari Pharma GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Pari Pharma GmbH
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP