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

• Sponsor: Pari Pharma GmbH (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01334892
• Collaborator: (none)
• Enrollment: 130
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 2.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Bronchiolitis Obliterans	Drug: Cyclosporine Inhalation Solution	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: L-CsA Twice daily inhalation of 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

Outcome Measures

Primary Outcome Measures

1. The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo. [2 years]

   BOS stage 1 and higher is considered as BOS for the primary endpoint.

Secondary Outcome Measures

1. Cumulative mean incidence of BOS 12, 18 and 24 months after first IMP administration [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

7. Tacrolimus and

8. Mycophenolate mofetil (MMF) 1 to 3 g/day and

9. Prednisone or any other steroid therapy; tapered down

10. Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration.

11. 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

Locations

	Site	City	State	Country	Postal Code
1	PARI Pharma GmbH	Graefelfing		Germany	82166

Sponsors and Collaborators

• Pari Pharma GmbH

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pari Pharma GmbH
• ClinicalTrials.gov Identifier: NCT01334892
• Other Study ID Numbers: 12011.201; 2008-003800-73; ISRCTN66069132
• First Posted: Apr 13, 2011
• Last Update Posted: Apr 14, 2015
• Last Verified: Apr 1, 2015

• Additional relevant MeSH terms: Bronchiolitis; Bronchiolitis Obliterans; Cyclosporine; Cyclosporins

Study Results

No Results Posted as of Apr 14, 2015