E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bronchiolitis Obliterans Syndrome following Lung Transplantation |
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E.1.1.1 | Medical condition in easily understood language |
Bronchiolitis Obliterans Syndrome following Lung Transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029888 |
E.1.2 | Term | Obliterative bronchiolitis |
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 |
Phase 1: To identify an appropriate dose of itacitinib as a treatment for Grade 1 through 3 Bronchiolitis Obliterans Syndrome (BOS) following lung transplantation.
Phase 2: To evaluate the efficacy of itacitinib as a treatment for Grade 1 through 3 BOS following lung transplantation. |
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E.2.2 | Secondary objectives of the trial |
Phase 1 and 2: * To evaluate duration of FEV1 response in participants with Grade 1 through 3 BOS following lung transplantation who are treated with itacitinib. * To evaluate time to progression in participants with Grade 1 through 3 BOS following lung transplantation who are treated with itacitinib. * To evaluate quality of life outcomes in participants with Grade 1 through 3 BOS following lung transplantation who are treated with itacitinib. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Male or female, 18 years of age or older. * Ability to comprehend and willingness to sign a written informed consent and assent (when appropriate) according to institutional standards and willingness to comply with all study visits and procedures. * Double lung transplantation ≥ 1 year before informed consent. * Documented post-transplant baseline FEV1 (average of the 2 highest values measured ≥ 3 weeks apart per ISHLT criteria [Meyer et al 2014]) following functional recovery and stabilization post–lung transplantation. * Confirmed BOS Grade 1, 2, or 3 (per ISHLT 2002 criteria [Estenne et al 2002]) diagnosed within 1 year of screening. - Grade 1 BOS is defined as a fractional decrease in FEV1 to 66-80% of post-transplant baseline FEV1. - Grade 2 BOS is defined as a fractional decrease in FEV1 to 51-65% of post-transplant baseline FEV1. - Grade 3 BOS is defined as a fractional decrease in FEV1 to ≤ 50% of post-transplant baseline FEV1. OR Confirmed BOS Grade 1, 2, or 3 diagnosed within 2 years of screening (based on the above definitions), AND: a) A ≥ 200 mL decrease in FEV1 in the previous 12 months OR b) A ≥ 50 mL decrease in FEV1 in the last 2 measurements.
* Willingness to avoid pregnancy or fathering children. * If a participant is being treated with a strong CYP3A inhibitor (see Appendix C), then the dose must be stable for > 4 weeks before the first dose of study drug. |
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E.4 | Principal exclusion criteria |
* History of a single lung transplant.
* FEV1 decline attributable to cause(s) other than BOS, including but not limited to clear evidence of RAS, inflammatory complications of the lung allograft, antibody mediated rejection, infection, airway dysfunction, allograft compression, impaired graft inflation, vascular obstruction, weight gain, or organizing pneumonia.
* For participants with Grade 3 BOS as defined in inclusion criterion #5, FEV1 at screening < 35% of post-transplant baseline.
* Receipt of any other systemic treatment specifically for BOS (with the exception of azithromycin and monteleukast), including extracorporeal photophoresis, alemtuzumab, and/or ATG within the timeframes outlined in the protocol (as applicable).
* Epstein-Barr virus-negative participants (at the time of transplant) who received donor EBV IgG positive lungs.
* Participants who have received lungs from HCV-infected donors.
* Active HBV or HCV infection that requires treatment, or at risk for HBV reactivation (i.e., positive HBsAg).
* Known HIV infection.
* Women who are pregnant or breastfeeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1: Frequency, severity, and duration of AEs; assessment of changes in safety and FEV1; and assessment of changes in laboratory parameters, PK, and PD.
Phase 2: FEV1 response rate from baseline through the Week 12 visit, defined as the proportion of participants demonstrating a ≥ 10% absolute increase in FEV1 compared to baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1: throughout the study
Phase 2: at Week 12 |
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E.5.2 | Secondary end point(s) |
Duration of FEV1 response: time of the onset of response (≥ 10% absolute increase in FEV1 compared to baseline) to BOS progression or loss of clinical benefit as determined by the investigator.
Time to progression: interval between the start of treatment and BOS progression (≥ 10% absolute decrease in FEV1 compared to baseline).
Quality of life: • Change from baseline in SGRQ total score. • Change from baseline in QOL-SF-12 questionnaire. • Change from baseline in EQ-5D-3L questionnaire. |
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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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
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 | No |
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 | No |
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 |
Canada |
United States |
Belgium |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of the study may be designated as the timepoint at which all participants have discontinued the study or a minimum of 6 months after initial study treatment administration, at which time a database lock of the study may occur to allow for analysis of the study data. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |