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

This study has been terminated.
(Interim analysis results revealed substantial increase of patient number, with unfeasible study prolongation.)
Sponsor:
Information provided by (Responsible Party):
Pari Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01334892
First received: April 11, 2011
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Bronchiolitis Obliterans
Drug: Cyclosporine Inhalation Solution
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Pari Pharma GmbH:

Primary Outcome Measures:
  • The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    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



Enrollment: 130
Study Start Date: December 2009
Estimated Study Completion Date: December 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: L-CsA
Twice daily inhalationof 2.5 ml/10 mg L-CsA for 96 weeks
Drug: Cyclosporine Inhalation Solution
Cyclosporin for inhalation twice daily
Placebo Comparator: L-CsA placebo
Twice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months)
Drug: Cyclosporine Inhalation Solution
Cyclosporin for inhalation twice daily

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334892

Locations
Germany
PARI Pharma GmbH
Graefelfing, Germany, 82166
Sponsors and Collaborators
Pari Pharma GmbH
  More Information

No publications provided

Responsible Party: Pari Pharma GmbH
ClinicalTrials.gov Identifier: NCT01334892     History of Changes
Other Study ID Numbers: 12011.201, 2008-003800-73, ISRCTN66069132
Study First Received: April 11, 2011
Last Updated: September 3, 2013
Health Authority: Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Denmark: National Board of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Bronchiolitis Obliterans
Bronchiolitis
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 27, 2014