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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 30 April 2019
Main ID:  EUCTR2018-003205-25-ES
Date of registration: 18/01/2019
Prospective Registration: Yes
Primary sponsor: BREATH Therapeutics Inc.
Public title: Clinical research study to investigate effectiveness and safety of Liposomal Cyclosporine A (L-CsA) in patients with Bronchiolitis obliterans syndrome after double lung transplantation.
Scientific title: A Phase III, Prospective, Multicenter, Randomized, Controlled Clinical Trial to Demonstrate the Effectiveness and Safety of Liposomal Cyclosporine A (L-CsA) Inhalation Solution Delivered via the PARI Investigational eFlow® Device plus Standard of Care versus Standard of Care Alone in the Treatment of Bronchiolitis Obliterans Syndrome in Patients post Double Lung Transplantation - BOSTON-2
Date of first enrolment: 01/03/2019
Target sample size: 110
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003205-25
Study type:  Interventional clinical trial of medicinal product
Study design: 
Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: yes
Other trial design description: Staff conducting spirometry, statisticians and data managers will be blinded to treatment assignment
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: yes
Other specify the comparator: Standard of Care
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Austria Belgium France Germany Israel Spain United Kingdom United States
Contacts
Name: Chief Medical Officer   
Address:  633 Menlo Avenue #230 CA 94025 Menlo Park United States
Telephone:
Email: contact@breath-therapeutics.com
Affiliation:  BREATH Therapeutics Inc.
Name: Chief Medical Officer   
Address:  633 Menlo Avenue #230 CA 94025 Menlo Park United States
Telephone:
Email: contact@breath-therapeutics.com
Affiliation:  BREATH Therapeutics Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
1. Adult patients of =18 years.
2. Patients with diagnosis of BOS Grade 0-p with screening FEV1 between 85-81% of personal best FEV1 value post transplant plus risk factors as defined below, OR BOS Grade 1 with screening FEV1 between 80-66% of personal best FEV1 value post-transplant. Patients with a diagnosis of BOS Grade 0-p must have = 2 of these risk factors for BOS:
- Primary graft dysfunction (PGD)
- Acute cellular rejection
- Lymphocytic bronchiolitis
- Humoral rejection (e.g. de novo anti-human leukocyte antigen antibodies)
- Gastro-oesophageal reflux and microaspiration
- Infection (Viral, Bacterial, Fungal)
- Persistent neutrophil influx and sequestration (bronchoalveolar lavage neutrophilia)
- Autoimmunity (collagen V sensitization).
3. Patients with an FEV1/FVC ratio of < 0.8.
4. Patients in whom the diagnosis of BOS has been confirmed by the elimination of other possible causes of obstructive lung disease.
5. Patients with a diagnosis of BOS 0-p or BOS 1 made at least 1 year after transplant surgery and within 6 months prior to the Screening Visit.
6. Patients receiving a tacrolimus-based basic immunosuppression regimen in combination with MMF (or equivalent) and corticosteroids. This basic immunosuppression regimen must be stable (without changes to doses) for at least 4-weeks prior to Randomization.
7. Patients must consent to retrieve prespecified data from the historic medical record (e.g., information related to the transplant surgery; spirometry data; medication use).
8. Patients must be receiving prophylaxis against Cytomegalovirus (CMV) and Pneumocystis pneumonia.
9. Patients capable of understanding the purposes and risks of the clinical trial, who have given written informed consent and agree to comply with the clinical trial requirements/visit schedules, and who are capable of aerosol inhalation.
10. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and must agree to use one of the methods of contraception listed in Appendix II for their duration of clinical trial participation.
11. Patients have no concomitant diagnoses that are considered fatal within one year (12 months).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
1. Patients with confirmed other causes for loss of lung function, such as infection, acute rejection, restrictive allograft syndrome (RAS), etc.
2. Cystic Fibrosis patients with multi-drug resistant infections not responding to available anti-microbial therapies.
3. Patients with donor-specific antibody (DSA) positivity at the Screening Visit.
4. Active bacterial, viral, or fungal infection not successfully resolved at least 4 weeks prior to the Screening Visit.
5. Mechanical ventilation within 12 weeks prior to Randomization.
6. Patient has baseline resting oxygen saturation of < 89% on room air or use of supplemental oxygen.
7. History or presence of bronchial strictures or airway stents or airways requiring balloon dilatations to maintain patency.
8. Known hypersensitivity to L-CsA or to cyclosporine A.
9. Patients with chronic renal failure defined as serum creatinine > 2.5 mg/dL or requiring chronic dialysis.
10. Patients with liver disease and serum bilirubin > 3-fold upper normal value or transaminases > 2.5 upper normal value.
11. Patients with a history of malignancy, including post-transplant lymphoproliferative disorder, with the exception of treated, localized basal and squamous cell carcinomas.
12. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy over the course of the clinical trial.
13. Women who are currently breastfeeding.
14. Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to the Screening Visit. This is defined as any treatment that is implemented under an Investigational New Drug (IND) or compassionate use.
15. Patients who have received extracorporeal photophoresis (ECP) for treatment of BOS within 2 months prior to Randomization.
16. Patients who are currently participating in an interventional clinical trial.
17. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
18. Any co-existing medical condition that in the Investigator’s judgment will substantially increase the risk associated with the patient’s participation in the clinical trial.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Bronchiolitis Obliterans Syndrome in Patients post Double Lung Transplantation
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Intervention(s)

Product Name: Liposomal Cyclosporine A
Product Code: L-CsA
Pharmaceutical Form: Powder and solvent for nebuliser solution
INN or Proposed INN: Ciclosporin (Ciclosporinium)
CAS Number: 59865-13-3
Current Sponsor code: L-CsA
Other descriptive name: CICLOSPORIN A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)
Main Objective: To assess the efficacy and safety of add-on aerosolized L-CsA to Standard of Care therapy as compared to SoC therapy alone in the treatment of BOS in double lung transplant recipients.
Timepoint(s) of evaluation of this end point: Week 48
Secondary Objective: Not applicable
Primary end point(s): Mean change in FEV1 (mL) from baseline.
Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • Week 48
• Time to Progression

Secondary end point(s): • Mean change in FEV1/FVC from baseline;
• Time to Progression of BOS, defined as the earliest of the following:
- Absolute decrease from baseline in FEV1 =10% or =200 mL and absolute decrease in FEV1/FVC of > 5%, OR
- Change in BOS Grade, OR
- Re-transplantation, OR
- Death from respiratory failure
This endpoint will be assessed in a combined analysis with a similar Phase III clinical trial, BT – L-CsA – 302 – DLT (BOSTON-2) which will be conducted in the same investigational centers in patients who have undergone double-lung transplantations.
Secondary ID(s)
2018-003205-25-DE
BT-L-CsA-302-DLT
NCT03656926
Source(s) of Monetary Support
BREATH Therapeutics Inc.
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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