E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bronchiolitis Obliterans Syndrome in Patients post Single or post Double Lung Transplantation
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E.1.1.1 | Medical condition in easily understood language |
Bronchiolitis Obliterans Syndrome in Patients after Single or post Double Lung Transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049202 |
E.1.2 | Term | Bronchiolitis obliterans |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the long-term safety and efficacy of L-CsA plus SoC in the treatment of BOS in single and double lung transplant recipients |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who have completed all visits through the End of Treatment Visit in either BOSTON-1 or BOSTON-2, did not withdraw informed consent, and did not prematurely terminate study drug administration. 2. Patients should be on a maintenance regimen of immunosuppressive agents as defined in the Boston 1 and Boston 2 studies, (i.e. tacrolimus, a second agent such as but not limited to mycophenolate mofetil (MMF) or azathioprine, and a systemic corticosteroid such as prednisone as third agent. Concomitant azithromycin for prophylaxis or treatment of BOS is also allowed), or according to Investigator judgment. 3. 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. 4. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to Visit 1 and must agree to use one of the methods of contraception listed in Appendix II of the protocol through their End of Study Visit. |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to L-CsA or to cyclosporine A. 2. Patients who experienced an AE related to study drug that led to permanent study drug discontinuation in BOSTON-1 or BOSTON-2. 3. Patients who developed a new malignancy while participating in BOSTON-1 or BOSTON-2, including post-transplant lymphoproliferative disorder, with the exception of treated, localized basal and squamous cell carcinomas. 4. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit. 5. Women who are currently breastfeeding. 6. Receipt of an investigational drug, other than L-CsA, as part of a clinical trial within 4 weeks prior to Visit 1. This is defined as any treatment that is implemented under an Investigational New Drug (IND) or compassionate use. 7. Patients who are currently participating in an interventional clinical trial, other than BOSTON-1 or BOSTON-2. 8. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures. 9. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
SAFETY 1 Adverse events (AEs) 2 Acute tolerability of IMP after initial dosing (only in patients randomized to SoC in BOSTON-1 or BOSTON-2 study) 3 Clinical laboratory parameters 4 Vital signs 5 Physical examinations 6 Renal function
EFFICACY 1 Mean change in forced expiratory volume in 1 second (FEV1) (mL) from baseline to approximately each year until End of Study in periods of 48 Weeks 2 Mean change in FEV1/forced vital capacity (FVC) from baseline to approximately each year until End of Study in periods of 48 Weeks 3 Time to progression of BOS, defined as the earliest of the following: o Absolute decrease from baseline in FEV1 ≥ 10% or ≥ 200 mL and absolute decrease in FEV1/FVC of > 5%, OR o Worsening of BOS grade (according to criteria in Verleden 2019), OR o Re-transplantation, OR o Death from respiratory failure 4 Rate of decline of FEV1 from baseline to last treatment day 5 Use of additional immunosuppressive therapy 6 Proportion of patients experiencing re-transplantation due to BOS 7 Proportion of patients with fatal outcome due to respiratory failure 8 Change in BOS severity (according to criteria in Verleden 2019) 9 Mean relative intra-individual change of FEV1 between start of treatment (baseline) and end of study participation 10 Absolute and relative change from baseline in: o Forced mid-expiratory flow (FEF25-75) o Forced Vital Capacity (FVC) 11 Euro Quality of Life Questionnaire (EQ-5D-5L) 12 Hospitalization days |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
SAFETY 1 Permanent assessment throughout the complete study period 2 Day 1 3, 4, and 5: W0 - EoS
EFFICACY From baseline to EoS |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open label extension study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Israel |
United Kingdom |
United States |
Austria |
Belgium |
France |
Germany |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |