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

NCT ID: NCT01334892

Last Updated: 2015-04-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2014-12-31

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.

Conditions

Bronchiolitis Obliterans

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

L-CsA

Twice daily inhalation of 2.5 ml/10 mg L-CsA for 96 weeks

Group Type: ACTIVE_COMPARATOR

Cyclosporine Inhalation Solution

Intervention Type: DRUG

Cyclosporin for inhalation twice daily

L-CsA placebo

Twice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months)

Group Type: PLACEBO_COMPARATOR

Cyclosporine Inhalation Solution

Intervention Type: DRUG

Cyclosporin for inhalation twice daily

Interventions

Cyclosporine Inhalation Solution

Cyclosporin for inhalation twice daily

Intervention Type: DRUG

Eligibility 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

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pari Pharma GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

PARI Pharma GmbH

Gräfelfing, , Germany

Countries

Germany

Other Identifiers

2008-003800-73

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN66069132

Identifier Type: REGISTRY

Identifier Source: secondary_id

12011.201

Identifier Type: -

Identifier Source: org_study_id