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

Bronchiolitis Obliterans Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01334892
• Other study ID #: 12011.201
• Secondary ID: 2008-003800-73IS
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: April 11, 2011
• Last updated: April 13, 2015
• Start date: December 2009
• Est. completion date: December 2014

Study information

• Verified date: April 2015
• Source: Pari Pharma GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaDenmark: National Board of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesSpain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 130
• Est. completion date: December 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans

Intervention

Drug:
• Cyclosporine Inhalation Solution
Cyclosporin for inhalation twice daily

Locations

Country	Name	City	State
Germany	PARI Pharma GmbH	Graefelfing

Sponsors (1)

Lead Sponsor	Collaborator
Pari Pharma GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years	No
Secondary	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	2 years	Yes