Condition category
Respiratory
Date applied
25/06/2008
Date assigned
10/07/2008
Last edited
29/06/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Ms Stefanie Prante

ORCID ID

Contact details

Clinical Trial Manager
PARI Pharma GmbH
Steinerstrasse 15A
Munich
81369
Germany

Additional identifiers

EudraCT number

2008-003800-73

ClinicalTrials.gov number

NCT01334892

Protocol/serial number

CLP 12011.201

Study information

Scientific title

A phase III, multicentre, randomised, double-blind, placebo controlled clinical trial to investigate the efficacy and safety of 10 or 20 mg/day aerosolised liposomal ciclosporin A (L-CsA) versus aerosolised placebo in the prevention of bronchiolitis obliterans syndrome (BOS) in lung transplant (LT) patients

Acronym

L-CsA-LT

Study hypothesis

Current hypothesis as of 29/06/2015:
To assess the efficacy and safety of the addition of aerosolised L-CsA plus Standard of Care systemic immunosuppression as compared to aerosolised placebo plus Standard of Care therapy for prevention of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients.

Previous hypothesis:
To establish an investigational medicinal product (IMP) dosage with the most favourable risk-benefit ratio for the prevention of bronchiolitis obliterans (BO).

On 31/07/2008 the sponsor details of this trial changed to PARI Pharma GmbH (Germany). The previous sponsor was Chiltern International (Germany).

On 12/05/2009 the following countries were removed from the recruitment list of this record: Switzerland, France. At this time, this record was also updated to include changes to the trial dates; the initial dates at the time of registration were:
Overall trial start date: 01/11/2008
Overall trial end date: 01/01/2012

On 29/06/2015 the following changes were made to the trial record:
1. The scientific title was changed from 'A phase II, randomised, double-blind, placebo controlled, parallel group, dose-finding clinical trial to investigate the efficacy and safety of 10 and 20 mg/day aerosolised liposomal cyclosporin A (L-CsA) versus aerosolised placebo in the prevention of bronchiolitis obliterans (BO) in lung transplant (LT) patients ' to 'A phase III, multicentre, randomised, double-blind, placebo controlled clinical trial to investigate the efficacy and safety of 10 or 20 mg/day aerosolised liposomal ciclosporin A (L-CsA) versus aerosolised placebo in the prevention of bronchiolitis obliterans syndrome (BOS) in lung transplant (LT) patients'
2. The study design changed from 'Phase II multicentre randomised double-blind placebo-controlled parallel-group dose-finding clinical trial' to 'Phase III multicentre randomised double-blind placebo-controlled clinical trial'
3. The overall trial end date was changed from 01/08/2012 to 12/07/2013.
4. The target number of participants was changed from 60 to 200.
5. Spain and France were added and Denmark and USA were removed from the countries of recruitment.

Ethics approval

1. Austria: Ethics Committee of the University of Vienna and the AKH, 14/09/2009, ref: 345/2009
2. Belgium: Ethics Committee of the University of Brussels, Hospital Erasme, 14/09/2009, ref: P2009/175
3. Germany: Ethics Committee of the University of Munich (LMU), 14/07/2009, ref: 143-09
4. United Kingdom: Cambridgeshire 1 Research Ethics Committee, 27/08/2009, ref: 09/H0304/47
5. France: ETHICS COMMITTEE Est-III Hôpital de Brabois. Rue de Morvan – 54511 VANDOEUVRE-LES-NANCY Cedex, ref: 10.09.05
6. Spain: CEIC del hospital Universitari Vall d’Hebrón, Bacelona

Study design

Phase III multicentre randomised double-blind placebo-controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Bronchiolitis obliterans

Intervention

Current interventions as of 29/06/2015:
Basic immunosuppression: All participants regardless of treatment allocation will receive Standard of Care basic immunosuppression consisting of a triple drug therapy (TDT) of tacrolimus, prednisone, and mycophenolate mofetil.

After screening and consenting patients will be randomly assigned to one of the following treatments:

Treatment arm A (aerosolised L-CsA treatment plus Standard of Care therapy):
Single-Lung Transplant (SLTx) patients: L-CsA 5 mg/1.25 ml twice daily for 96 weeks (24 months)
Plus
Standard of Care systemic immunosuppression

Double-Lung Transplant (DLTx) patients:
L-CsA 10 mg/2.5 ml twice daily for 96 weeks (24 months)
Plus
Standard of Care systemic immunosuppression

Treatment arm B (aerosolised placebo treatment plus Standard of Care therapy):
Single-Lung Transplant (SLTx) patients:
Placebo 1.25 ml twice daily for 96 weeks (24 months)
Plus
Standard of Care systemic immunosuppression

Double-Lung Transplant (DLTx) patients:
Placebo 2.5 ml twice daily for 96 weeks (24 months)
Plus
Standard of Care systemic immunosuppression

Previous interventions from 12/05/2009 to 29/06/2015:
Subjects will be randomised (1:1:1) to one of three treatment arms:
1. 1 x 10 or 5 mg/day L-CsA and 1 x placebo/day
2. 2 x 10 or 5 mg/day L-CsA
3. 2 x placebo

Subjects will be stratified according to several baseline risk factors, e.g. double versus single lung transplantation. Treatment duration will be 96 weeks (2 years) with one month follow-up period.

Initial information at time of registration:
Subjects will be randomised (1:1:1) to one of three treatment arms:
1. 1 x 10 or 5 mg/day L-CsA and 1 x placebo/day
2. 2 x 10 or 5 mg/day L-CsA
3. 2 x placebo

Subjects will be stratified according to several baseline risk factors, e.g. double versus single lung transplantation. Treatment duration will be 96 weeks (2 years) with no follow-up period. After successful completion of the study, the patient may enter the follow-up clinical trial (ref: 12011.203) after fulfilling inclusion/exclusion criteria.

Intervention type

Drug

Phase

Phase III

Drug names

Liposomal cyclosporin A (L-CsA)

Primary outcome measures

Current primary outcome measures as of 29/06/2015:
BOS-free survival
Bronchiolitis obliterans syndrome (BOS)
Efficacy of L-CsA in preventing the development of bronchiolitis obliterans when given to lung transplant recipients in addition to Standard of Care systemic immunosuppression. Efficacy failure is the combined endpoint of occurrence of BOS (defined as at least a 20% decline from the initial randomization FEV1 value confirmed by two separate measurements of at least three weeks apart) or re-transplantation or death. BOS stage 1 and higher is considered as BOS for the primary endpoint. BOS-free survival is the time from first IMP intake to either first BOS or re-transplantation or death.

Previous primary outcome measures:
The primary objective is to establish an IMP dosage with the most favourable risk-benefit ratio for the prevention of BO in LT patients.

Secondary outcome measures

Current secondary outcome measures as of 29/06/2015:
1. Efficacy: Pulmonary function parameter, Incidence of BOS, overall survival, Incidence of graft loss
2. Safety: Treatment-emergent adverse events (AEs), incidence of invasive bacterial, viral or fungal infections, clinical laboratory, vital signs, physical examination and L-CsA and tacrolimus trough blood levels

Previous secondary outcome measures:
The secondary objectives are to compare efficacy and safety data from two different L-CsA doses versus placebo and to evaluate investigational medicinal product (IMP) pharmacokinetic (PK) data in bronchoalveolar lavage (BAL) and in whole blood samples.

Overall trial start date

01/06/2009

Overall trial end date

12/07/2013

Reason abandoned

Eligibility

Participant inclusion criteria

Current information as of 31/03/2010:
The following point has been amended as of the above date:
2. Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration

Previous information as of 12/05/2009:
1. Patient's written informed consent obtained prior to any screening procedure
2. Received a single lung, bilateral lung or heart/lung transplantation within four weeks prior to first investigational medical product (IMP) administration
3. Male or female greater than or equal to 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 within one week prior to first IMP administration the following immunosuppressive agents and dosages for maintenance therapy:
6.1. Tacrolimus approximately 0.1 to 0.2 mg/kg/day adjusted to a target serum level (C0, trough) of 8 to 15 µg/L, and
6.2. Mycophenolate mofetil (MMF) 1 to 3 g/day, and
6.3. Prednisone orally; tapered down within the first 3 months after transplantation
7. Female patients with childbearing potential must have a negative serum pregnancy test within 3 days prior to screening. Both women and men must agree to use a medically acceptable method of contraception throughout the IMP treatment period and for 3 months after IMP discontinuation.
8. Estimated life expectancy greater than 6 months

Initial information at time of registration:
1. Signed informed consent provided prior to any screening procedure
2. Male or female, 12 years or older
3. Capable of self-administrating medications
4. Capable of understanding the purpose and risk of the study
5. Received a single lung, bilateral lung or heart/lung transplantation within one week prior to first investigational medicinal product (IMP) administration
6. Received within one week prior to first IMP administration the following immunosuppressive agents and dosages for maintenance therapy:
6.1. Tacrolimus 0.1 to 0.2 mg/kg/day adjusted to target serum level (trough concentrations) of 8 to 15 µg/L
6.2. Mycophenolate mofetil (MMF) 1 to 3 g/day, and
6.3. Prednisone orally 0.5 mg/kg/day initial dosing tapered down to approximately 5 mg/week after 2 to 4 weeks
7. Female patients with child bearing potential must have a negative serum pregnancy test within 3 days prior to screening. Both women and men must agree to use a medically-acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include intra-uterine device (IUD), oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository)
8. Estimated life expectancy greater than 6 months

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

200

Participant exclusion criteria

Current information as of 12/05/2009:
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 within one week prior to first IMP administration
3. Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria within one week prior to first IMP administration
4. Received any systemic or topical ciclosporin A within one week prior to first IMP administration and/or during the clinical trial
5. Received any systemic or topical rosuvastatin within one week prior to first IMP administration and/or during the clinical trial
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) or chronic dialysis (haemodialysis)
11. Unlikely to comply with visits, inhalation procedures or spirometric measurements scheduled in the protocol
12. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to first administration of IMP
13. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the clinical trial
14. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures
15. Patient was previously enrolled in the present clinical trial

Initial information at time of registration:
1. Any previous episode of acute rejection of grade A2 or higher
2. Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher
3. An active invasive bacterial, viral or fungal infection within one week prior to IMP administration
4. Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria within one week prior to first IMP administration
5. Received any systemic or topical cyclosporin within one week prior to first IMP administration and/or during the clinical trial
6. Received mechanical ventilation
7. Received a lung re-transplantation
8. Pregnant or breast feeding woman
9. Has known hypersensitivity to cyclosporin A
10. Has a serum creatinine value of more than 3 mg/dL
11. Unlikely to comply with visits, inhalation procedures or spirometric measurements scheduled in the protocol
12. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to first administration of IMP
13. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the subject's participation in the study
14. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures
15. Has been previously enrolled in this study

Recruitment start date

01/06/2009

Recruitment end date

01/08/2012

Locations

Countries of recruitment

Austria, Belgium, France, Germany, Spain, United Kingdom

Trial participating centre

PARI Pharma GmbH
Munich
81369
Germany

Sponsor information

Organisation

PARI Pharma GmbH (Germany)

Sponsor details

Lochhamer Schlag 21
Graefelfing
82166
Germany

Sponsor type

Industry

Website

http://www.paripharma.com

Funders

Funder type

Industry

Funder name

PARI Pharma GmbH (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes