Bronchiolitis Obliterans Syndrome following Lung Transplantation MedDRA version: 20.0 Level: LLT Classification code 10049202 Term: Bronchiolitis obliterans System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 21.1 Level: PT Classification code 10029888 Term: Obliterative bronchiolitis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: itacitinib
Product Code: INCB039110
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: ITACITINIB
CAS Number: 1334298-90-6
Current Sponsor code: INCB039110
Other descript
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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.;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.;Timepoint(s) of evaluation of this end point: Phase 1: throughout the study Phase 2: at Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;Timepoint(s) of evaluation of this end point: throughout the study | — |
Countries
Belgium, Canada, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed