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 disorders MedDRA version: 20.1 Level: PT Classification code 10072158 Term: Chronic graft versus host disease in intestine System Organ Class: 10021428 - Immune sy
Conditions
Interventions
Product Name: Itacitinib
Product Code: INCB039110
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: itacitinib
CAS Number: 1334302-63-4
Current Sponsor code: INCB039110
Other descrip
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 107
Exclusion criteria
Exclusion criteria: 1. Has received more than 1 prior allo-HCT. Prior autologous HCT is allowed. 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. CNIs initiated before randomization may be continued at the same or lower dose; topical/inhaled steroids are acceptable. 4. Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for aGVHD are eligible only if they achieved CR or PR.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 and Part 1 expansion: 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 1 Expansion: - To evaluate preliminary activity across treatment cohorts with respect to response rate at Month 3 and Month 6 (Key secondary objective) - To evaluate the PK of itacitinib when administered in combination with corticosteroids in the study population. - To estimate efficacy outcomes for each dose cohort. *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 1 expansion: Incidence and severity of adverse events, across treatment cohorts. 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 1 Expansion: throughout Part 1 expansion duration 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 1 Expansion: - for the Key secondary objective: response rate at Month 3 and Month 6, defined as the proportion of participants who demonstrate a CR or PR at each timepoint. - Response rate at Month 12. - Cmax, Cmin, Tmax, AUC0-t, and Cl/F; - Response rate at Month 3, 6 and 12; - Duration of response - OS - NMR - 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, PGIC and PGIS. - Response rate at Month | — |
Countries
Austria, Belgium, Canada, Denmark, Finland, France, Germany, Greece, Israel, Italy, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed