Bronchiolitis ObliteransPhase 2/3NCT01334892
L-CsA in the Prevention of Bronchiolitis Obliterans Syndrome (BOS) in Lung Transplant (LT) Patients
A Phase 2/3 study testing Cyclosporine Inhalation Solution in people with Bronchiolitis Obliterans, run by Pari Pharma GmbH at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bronchiolitis Obliterans
- What is being tested?
- Cyclosporine Inhalation Solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2009to Dec 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient's written informed consent
- Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration.
- Male or female, 18 years of age
- Capable of self-administration of medications
- Capable of understanding the purpose and risk of the clinical trial
- Received the following immunosuppressive agents and dosages for maintenance therapy:
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- Tacrolimus and
- Mycophenolate mofetil (MMF) 1 to 3 g/day and
- Prednisone or any other steroid therapy; tapered down
- Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration.
- Estimated life expectancy > 6 month
Who cannot join
- Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher
- Any active invasive bacterial, viral or fungal infection
- Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria
- Received any systemic or topical ciclosporin A within
- Received any systemic or topical Rosuvastatin
- Current mechanical ventilation
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- Received a lung re-transplantation
- Pregnant or breast feeding woman
- Has known hypersensitivity to ciclosporin A
- Has a serum creatinine value of more than 265 µmol/L (3 mg/dL)
- Unlikely to comply with visits, inhalation procedures or spirometric measurements
- Receipt of an investigational drug within 4 weeks prior to first administration of IMP
- Any co-existing medical condition that in the investigator's judgement
- Psychiatric disorders or altered mental status
- Patient was previously enrolled in the present clinical trial
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Cyclosporine Inhalation Solution
- Medical subject headings
- Bronchiolitis Obliterans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclosporine Inhalation SolutionDrug
Cyclosporin for inhalation twice daily
| Study group | Role | What they receive |
|---|---|---|
| L-CsA | Active comparator | Twice daily inhalation of 2.5 ml/10 mg L-CsA for 96 weeks Receives: Drug: Cyclosporine Inhalation Solution |
| L-CsA placebo | Placebo comparator | Twice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months) Receives: Drug: Cyclosporine Inhalation Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (1)
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2011 (estimated)
- Study startDec 2009
- Primary completionJul 2013
- Study completionDec 2014
Why it stopped: Interim analysis results revealed substantial increase of patient number, with unfeasible study prolongation.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bronchiolitis ObliteransStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pari Pharma GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01334892
- Sponsor's protocol ID
- 12011.201
- Other IDs
- 2008-003800-73, ISRCTN66069132, 2008
- Status last verified
- Apr 2015
- First submitted
- 11 Apr 2011
- Last updated
- 14 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01334892
- Acronym / sponsor ID
- 12011.201
- Conditions
- Bronchiolitis Obliterans
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis results revealed substantial increase of patient number, with unfeasible study prolongation.
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Pari Pharma GmbHIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Jul 2013 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 13 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-CsA | Active comparator | Drug: Cyclosporine Inhalation SolutionTwice daily inhalation of 2.5 ml/10 mg L-CsA for 96 weeks |
| L-CsA placebo | Placebo comparator | Drug: Cyclosporine Inhalation SolutionTwice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patient's written informed consent
- Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration.
- Male or female, 18 years of age
- Capable of self-administration of medications
- Capable of understanding the purpose and risk of the clinical trial
Key exclusion criteria (15 listed)
- Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher
- Any active invasive bacterial, viral or fungal infection
- Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria
- Received any systemic or topical ciclosporin A within
- Received any systemic or topical Rosuvastatin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclosporine Inhalation SolutionCyclosporin for inhalation twice daily | Drug | L-CsA, L-CsA placebo |
Primary outcome
The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo.
Time frame: 2 years
BOS stage 1 and higher is considered as BOS for the primary endpoint.
1 secondary outcome
Cumulative mean incidence of BOS 12, 18 and 24 months after first IMP administration
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Interim analysis results revealed substantial increase of patient number, with unfeasible study prolongation.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Cyclosporine Inhalation Solution in people with Bronchiolitis Obliterans, run by Pari Pharma GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Interim analysis results revealed substantial increase of patient number, with unfeasible study prolongation.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2015.