Clinical research study to investigate efficacy and safety of LiposomalCyclosporine A (L-CsA) in patients with Bronchiolitis obliterans syndromeafter double lung transplantation.
- Conditions
- Chronic Lung Allograft Dysfunction / Bronchiolitis Obliterans Syndromein Patients post Double Lung TransplantationTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-003205-25-AT
- Lead Sponsor
- Zambon SpA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 170
1. Adult patients of = 18 years who received a double lung transplant at
least 12 months prior to Screening.
2. Patients with BOS diagnosis defined as CLAD-BOS phenotype with:
a) Screening FEV1 between 85-51% of personal best FEV1 value posttransplant.
OR
b) Screening FEV1 >85% of personal best FEV1 associated with EITHER
a = 200 mL decrease in FEV1 in the previous 12 months OR according to
medical history showing BOS progression.
3. Diagnosis of CLAD-BOS must be made at least 12 months after lung
transplantation and
a) within 12 months prior to the screening visit.
OR
b) more than 12 months from screening and patient must have shown a
decline in FEV1 = 200ml in the previous 12 months before screening,
which is not due to acute infection or acute organ rejection.
4. Patients in whom the diagnosis of BOS has been confirmed by the
elimination of other possible causes of obstructive or restrictive lung
disease (CLAD – RAS phenotype, see Protocol Specific Definitions).
5. Patients should be on a drug maintenance regimen of
immunosuppressive agents including tacrolimus, a second agent such as
but not limited to MMF or azathioprine, and a systemic corticosteroid
such as prednisone as third agent. The regimen must be stable within 4
weeks prior to randomization with respect to the therapeutic agents. In
case a patient is also receiving concomitant azithromycin for
prophylaxis or treatment of BOS, in addition to the previously described
immunusuppresive regimen , azythromicin regimen must be on a stable
regimen for a least 4-weeks prior to randomization.
6. 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. Patients must consent to retrieve
prespecified data from the historic medical record (e.g., information
related to the transplant surgery; spirometry data; medication use).
7. Women of childbearing potential must have a negative serum or urine
pregnancy test within 7 days prior to randomization and must agree to
use one of the methods of contraception listed in Appendix II of the
protocol through their End of Study Visit.
8. Patients have no concomitant diagnoses that are considered fatal
within one year (12 months) of Screening.
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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
1. Patients with confirmed other causes for loss of lung function, such as
acute infection, acute rejection, restrictive allograft syndrome (CLAD –
RAS phenotype, see Protocol Specific Definitions),etc.
2. Cystic Fibrosis patients with multi-drug resistant infections not
responding to available anti-microbial therapies.
3. Patients with acute antibody-mediated rejection at Screening. In this
context, clinically stable patients (as judged by the Investigator) with
detectable levels of donor specific antibodies (DSA) at the Screening
Visit are eligible for the study.
4. Active bacterial, viral, or fungal infection not successfully resolved at
least 4 weeks prior to the Screening Visit. Patients with chronic
infection or colonization who are clinically stable as per judgement of
the Investigator are eligible for the study
5. Mechanical ventilation (including CPAP) within 12 weeks prior to Randomization.
6. Patients with uncontrolled hypertension.
7. Patient has baseline resting oxygen saturation of < 89% on room air
or use of supplemental oxygen at rest.
8. Evidence of functional airway stenosis (e.g.,
bronchomalacia/tracheomalacia, airway stents, or airways requiring
balloon dilatations to maintain patency) with onset after the initial
diagnosis of BOS and ongoing at Screening and/or Randomization Visit.
9. Known hypersensitivity to L-CsA or cyclosporine A.
10. Patients with chronic renal failure defined as serum creatinine > 2.5
mg/dL at screening or requiring chronic dialysis.
11. Patients with liver disease and serum bilirubin > 3-fold upper limit of
normal range or transaminases > 2.5 upper limit of normal range.
12. Patients with active malignancy within the previous 2 years,
including post-transplant lymphoproliferative disorder, with the
exception of treated, localized basal and squamous cell carcinomas.
13. Pregnant women or women who are unwilling to use appropriate
birth control to avoid pregnancy through their End of Study Visit.
14. Women who are currently breastfeeding.
15. 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.
16. Patients who have received extracorporeal photophoresis (ECP) for
treatment of BOS within 1 month prior to Randomization.
17. Patients who are currently participating in an interventional clinical
trial.
18. Psychiatric disorders or altered mental status precluding
understanding of the informed consent process and/or completion of the
necessary procedures.
19. 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.;Secondary Objective: Not applicable;Primary end point(s): Mean change in FEV1 (mL) from baseline.;Timepoint(s) of evaluation of this end point: Week 48
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Mean change in FEV1/FVC from baseline;<br>• Time to Progression of BOS, defined as the earliest of the following:<br>- Absolute decrease from baseline in FEV1 = 10% or = 200 mL and absolute decrease in FEV1/FVC of > 5%, OR<br>- Worsening in BOS grade, OR<br>- Re-transplantation, OR<br>- Death from respiratory failure;Timepoint(s) of evaluation of this end point: • Week 48<br>• Time to Progression