Moderate or severe cGVHD MedDRA version: 20.1 Level: PT Classification code 10066261 Term: Chronic graft versus host disease System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.1 Level: PT Classification code 10072160 Term: Chronic graft versus host disease in liver System Organ Class: 10021428 - Immune system dis
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, aged 18 years or older inclusive at the time of signing the ICF. 2. Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria : a. Moderate cGVHD: At least 1 organ (except lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1. b. Severe cGVHD: At least 1 organ with a score of 3, or lung score of 2 or 3. Note: Candidates who transition from active aGVHD to cGVHD without tapering off of corticosteroids (=65 years) yes F.1.3.1 Number of subjects for this age range 53
Exclusion criteria
Exclusion criteria: 1. Has received more than 1 prior allo-HCT. 2. Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD. 3. Has received any other systemic treatment for cGVHD, including ECP. Prior and concomitant use of CNIs as well as topical/inhaled steroids is acceptable. 4. Prior treatment with a JAK inhibitor for aGVHD, unless the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks before randomization. 5. cGVHD occurring after a nonscheduled DLI administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD. Part 2: To compare the efficacy of itacitinib versus placebo in combination with corticosteroids as initial treatment for moderate or severe cGVHD. ; Secondary Objective: Part 1: - To evaluate the PK of itacitinib when administered in combination with corticosteroids in the study population. - To estimate efficacy outcomes. Part 2: - To compare changes in health-related quality of life. - To compare additional efficacy outcomes between treatment groups. - To evaluate the PK of itacitinib in combination with corticosteroids in 1L cGVHD. - To evaluate the safety and tolerability of study treatment across the 2 treatment cohorts. ; Primary end point(s): Part 1: DLT data through Day 28 and additional data from clinical safety and laboratory assessments. Part 2: Response rate at Month 6, defined as the proportion of participants demonstrating a CR or PR at Month 6. ; Timepoint(s) of evaluation of this end point: Part 1: through Day 28 part 2: at Month 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: - Cmax, Cmin, Tmax, AUC0-t, and Cl/F. - Response rate at Month 3, 6, and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint. - Time to response, defined as the interval between randomization and first response. - DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy. - OS, defined as the interval between the date of randomization and the date of death due to any cause. - NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease. - Proportion of participants with = 50% reduction in daily corticosteroid dose at Day 180. - Proportion of participants successfully tapered off all corticosteroids at Day 180. - Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses. - Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse. Part 2: - Changes in symptom scores using the LSS, QOL-SF-36 v2, and EQ-5D-3L. - Response rate at Month 3 and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint. - DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy. - OS, defined as the interval between the date of randomization and the date of death due to any cause. - NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease. - Proportion of participants w | — |
Countries
Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed