Graft-versus-host Disease (GVHD)
Conditions
Keywords
Graft-versus-host disease (GvHD), Chronic GvHD (cGvHD), steroid-refractory, ruxolitinib, Janus kinase inhibitor
Brief summary
The purpose of this study is to assess the efficacy of ruxolitinib against best available therapy in participants with steroid-refractory chronic graft-versus-host disease (SR cGvHD).
Interventions
DRUGRuxolitinib
Ruxolitinib twice daily at the protocol-defined starting dose.
Best available therapy (BAT) will be selected by the investigator for each participant. BAT may not include experimental agents (ie, those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. The BAT in this study will be among the following treatments currently used in this setting (no other types or combinations of BATs are permitted in this study).
DRUGLow-dose methotrexate (MTX)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
DRUGMycophenolate mofetil (MMF)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
DRUGmechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
DRUGInfliximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
DRUGRituximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
DRUGPentostatin
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
DRUGImatinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
DRUGIbrutinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have undergone allogeneic stem cell transplantation (alloSCT) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible * Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) \> 1000/mm\^3 and platelet count \> 25,000/ mm\^3 * Participants with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria prior to randomization: * Moderate cGvHD: At least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1 * Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3 * Participants currently receiving systemic or topical corticosteroids for the treatment of cGvHD for a duration of \< 12 months prior to Cycle 1 Day 1 (if applicable), and have a confirmed diagnosis of steroid-refractory cGvHD defined per 2014 NIH consensus criteria irrespective of the concomitant use of a calcineurin inhibitor (CNI), as follows: * A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, OR * Disease persistence without improvement despite continued treatment with prednisone at \> 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR * Increase to prednisolone dose to \> 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose * Participant must accept to be treated with only one of the following BAT options on Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib
Exclusion criteria
* Participants who have received 2 or more systemic treatment for cGvHD in addition to corticosteroids ± CNI for cGvHD * Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment \* Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed. * Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1 * Failed prior alloSCT within the past 6 months from Cycle 1 Day 1 * Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed * Steroid refractory cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for preemptive 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 * Any corticosteroid therapy for indications other than cGvHD at doses \> 1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit | Cycle 7 Day 1 (each cycle was comprised of 4 weeks) | ORR was defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Failure-free Survival (FFS) | Baseline to when the last participant reached Cycle 7 Day 1 (each cycle was comprised of 4 weeks) | Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD. |
| Rate of FFS at Study Completion | From Baseline to Last Participant Last Visit (LPLV) (approximately 5 years) | Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD. |
| Best Overall Response (BOR) at Cycle 7 Day 1 | up to Cycle 7 Day 1 (each cycle was comprised of 4 weeks) | BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. This analysis was based on the primary cutoff date (May 2020). |
| BOR During Cross-over Treatment With Ruxolitinib | from Crossover Cycle 1 Day 1 to any time point up to and including Crossover Cycle 7 Day 1 (each cycle was comprised of 4 weeks) | BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. |
| ORR at the End of Cycle 3 | Cycle 4 Day 1 (each cycle was comprised of 4 weeks) | ORR was defined as the percentage of participants in each arm demonstrating a CR or PR based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. |
| Duration of Response Through Study Completion | from first response to LPLV (approximately 5 years) | DOR was defined as the time from first response until cGvHD progression, death, or the date of change/addition of systemic therapies for cGvHD and as assessed for responders only. Response was based on cGvHD disease assessments (National Institutes of Health consensus criteria). Duration of response was evaluated in participants who achieved a CR or PR at or before Cycle 7 Day 1. The analysis included a larger number of participants than the number of participants who achieved CR or PR at Cycle 7 Day 1 (82 ruxolitinib and 42 BAT) because the analysis took into account not only those participants who achieved CR or PR at Cycle 7 Day 1, but also participants who achieved CR or PR before Cycle 7 Day 1 but who may have lost their response at Cycle 7 Day 1. For this reason, the number of participants in this analysis does not align with the best overall response (BOR) at Cycle 7 Day 1. This analysis was based on the cutoff date upon study completion (December 2022). |
| Overall Survival (OS) | from the date of randomization to the date of death due to any cause up to LPLV (approximately 5 years) | Overall survival was defined as the time from the date of randomization to the date of death due to any cause. |
| Cumulative Incidence of Non-relapse Mortality (NRM) | Months 3, 6, 12, 18, 24, 30, and 36 | Defined as the cumulative incidence rate from competing risk analysis for NRM from the date of randomization to the date of death not preceded by underlying disease relapse/recurrence. |
| Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | from Day 15 up to Day 182 | All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants with a ≥ 50% reduction in daily corticosteroid dose. |
| Percentage of Participants Successfully Tapered Off of All Corticosteroids | up to Day 179 | All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants who successfully tapered off of all corticosteroids. Participants who completely tapered off corticosteroids refer to those who permanently discontinued steroids as per the dose administration panel and who did not restart steroids in the same interval. Participants who were tapered off and continued follow-up were also counted as being tapered off with 0 dose in subsequent intervals until they discontinued from the main treatment period or restarted steroid treatment. |
| Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | Months 3, 6, 12, 18, 24, 30, and 36 | Defined as the cumulative incidence rate from competing risk analysis of MR from the date of randomization to hematologic malignancy relapse/recurrence. |
| Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score | Baseline; Cycle 7 Day 1 (each cycle was comprised of 4 weeks) | To assess improvement of symptoms based on the total symptom score (TSS); a responder was defined as having achieved a clinically relevant reduction from Baseline of the TSS. The scale consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy, and psychological). Participants reported their level of symptom bother over the previous month on a 5-point likert scale: not at all, slightly, moderately, quite a bit, or extremely. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms. |
| Change From Baseline in EQ-5D-5L | Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks) | The EQ-5D-5L is a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point Likert scale, with 1 being no problems and 5 being extreme problems. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | from Baseline to LPLV (approximately 5 years) | Adverse events were defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occurred after the participant's signed informed consent was obtained. Abnormal laboratory values or test results occurring after informed consent constituted adverse events only if they induced clinical signs or symptoms, were considered clinically significant, required therapy (e.g., hematologic abnormality that required transfusion or hematological stem cell support), or required changes in study medication(s). TEAEs were defined as those AEs that started or worsened during the on-treatment period (either randomized or cross-over period). |
| Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose | Cmax was defined as the maximum observed plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule. |
| AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose | AUClast was defined as the area under the concentration-time curve up to the last measurable concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule. |
| AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose | AUCinf was defined as the area under the concentration-time curve from time 0 to infinity. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule. |
| CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose | CL/F was defined as the oral dose clearance of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule. |
| Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose | Vz/F was defined as the apparent oral dose volume of distribution of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule. |
| Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose | tmax was defined as the time to reach the maximum plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule. |
| t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose | t1/2 was defined as the apparent terminal phase disposition half-life of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule. |
| Utilization of Medical Resources | from Baseline to LPLV (approximately 5 years) | The percentage of participants with at least one submission to healthcare encounter was assessed. |
| Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks) | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The FACT-BMT is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family, and emotional well-being, together with additional concerns relevant for bone marrow transplantation participants. The questions were based on a 5-point Likert scale, where 0 corresponds to not at all and 4 corresponds to very much. The higher the final score, the better the quality of life. The FACT-BMT total score ranges from 0 to 148. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Jordan, Netherlands, Norway, Poland, Portugal, Puerto Rico, Romania, Russia, Saudi Arabia, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in 29 countries globally. During the main treatment period, participants were randomly assigned to a ruxolitinib arm or a Best Available Therapy (BAT) arm for 6 cycles of treatment. At the end of Cycle 6, participants in the BAT arm either crossed over to ruxolitinib treatment or entered the survival follow-up phase.
Pre-assignment details
A total of 404 participants were screened, of whom 72 were screen failures and 3 were not randomized for various reasons. Out of the 329 participants randomized, 6 did not receive BAT due to logistical reasons. A total of 329 participants were included in the Full Analysis Set (FAS); 165 were in the ruxolitinib arm and 164 were in the BAT arm.
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib Ruxolitinib was administered orally twice per day at a dose of 10 milligrams (mg). | 165 |
| Best Available Therapy Participants received best available therapies (BATs), including, but not limited to, extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, and ibrutinib based on the investigator's decision. | 164 |
| Total | 329 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| End of Cross Over Period | Adverse Event | 0 | 0 | 6 |
| End of Cross Over Period | Death | 0 | 0 | 2 |
| End of Cross Over Period | Disease Relapse | 0 | 0 | 2 |
| End of Cross Over Period | Lack of Efficacy | 0 | 0 | 8 |
| End of Cross Over Period | Participant/Guardian Decision | 0 | 0 | 7 |
| End of Cross Over Period | Physician Decision | 0 | 0 | 29 |
| End of Randomization Period | Adverse Event | 32 | 12 | 0 |
| End of Randomization Period | Death | 10 | 7 | 0 |
| End of Randomization Period | Disease Relapse | 12 | 7 | 0 |
| End of Randomization Period | Failure to Meet Protocol Continuation Criteria | 4 | 5 | 0 |
| End of Randomization Period | Lack of Efficacy | 25 | 77 | 0 |
| End of Randomization Period | Lost to Follow-up | 3 | 0 | 0 |
| End of Randomization Period | Participant/Guardian Decision | 7 | 14 | 0 |
| End of Randomization Period | Physician Decision | 43 | 18 | 0 |
Baseline characteristics
| Characteristic | Total | Best Available Therapy | Ruxolitinib |
|---|---|---|---|
| Age, Continuous | 46.5 Years STANDARD_DEVIATION 15.92 | 47.2 Years STANDARD_DEVIATION 16.17 | 45.9 Years STANDARD_DEVIATION 15.68 |
| ECOG Performance Status 0 | 81 Participants | 42 Participants | 39 Participants |
| ECOG Performance Status 1 | 174 Participants | 82 Participants | 92 Participants |
| ECOG Performance Status 2 | 44 Participants | 22 Participants | 22 Participants |
| ECOG Performance Status 3 | 2 Participants | 2 Participants | 0 Participants |
| ECOG Performance Status Missing | 28 Participants | 16 Participants | 12 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 54 Participants | 21 Participants | 33 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 26 Participants | 13 Participants | 13 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 233 Participants | 115 Participants | 118 Participants |
| Race/Ethnicity, Customized Not Reported | 51 Participants | 25 Participants | 26 Participants |
| Race/Ethnicity, Customized Other | 13 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown | 10 Participants | 11 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 248 Participants | 132 Participants | 116 Participants |
| Sex: Female, Male Female | 128 Participants | 72 Participants | 56 Participants |
| Sex: Female, Male Male | 201 Participants | 92 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 37 / 165 | 40 / 158 | 10 / 70 |
| other Total, other adverse events | 158 / 165 | 132 / 158 | 62 / 70 |
| serious Total, serious adverse events | 86 / 165 | 71 / 158 | 27 / 70 |
Outcome results
Primary
Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit
ORR was defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.
Time frame: Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Population: Full Analysis Set (FAS): all participants to whom study treatment was assigned by randomization. Data reported are from the start of the study to Cycle 7 Day 1 (data cutoff of 08 May 2020).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit | 49.7 percentage of participants |
| Best Available Therapy | Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit | 25.6 percentage of participants |
p-value: <0.000195% CI: [1.86, 4.8]Cochran-Mantel-Haenszel
Secondary
AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
AUCinf was defined as the area under the concentration-time curve from time 0 to infinity. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule.
Time frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Population: PAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 1 | 642 ng*hour/mL | Geometric Coefficient of Variation 32.7 |
Secondary
AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
AUClast was defined as the area under the concentration-time curve up to the last measurable concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule.
Time frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Population: PAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 1 | 636 ng*hour/mL | Geometric Coefficient of Variation 40.8 |
| Ruxolitinib | AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 15 | 945 ng*hour/mL | Geometric Coefficient of Variation 56.1 |
Secondary
Best Overall Response (BOR) at Cycle 7 Day 1
BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. This analysis was based on the primary cutoff date (May 2020).
Time frame: up to Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Population: FAS. Data reported are from the start of the study to Cycle 7 Day 1 (data cutoff of 08 May 2020).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | Best Overall Response (BOR) at Cycle 7 Day 1 | 76.4 percentage of participants |
| Best Available Therapy | Best Overall Response (BOR) at Cycle 7 Day 1 | 60.4 percentage of participants |
p-value: 0.001195% CI: [1.34, 3.52]Cochran-Mantel-Haenszel
Secondary
BOR During Cross-over Treatment With Ruxolitinib
BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.
Time frame: from Crossover Cycle 1 Day 1 to any time point up to and including Crossover Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Population: Cross-over Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | BOR During Cross-over Treatment With Ruxolitinib | 81.4 percentage of participants |
Secondary
Change From Baseline in EQ-5D-5L
The EQ-5D-5L is a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point Likert scale, with 1 being no problems and 5 being extreme problems.
Time frame: Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)
Population: FAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 3 Day 1 | 0.03 scores on a scale | Standard Deviation 0.221 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 18 Day 1 | 0.07 scores on a scale | Standard Deviation 0.299 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 7 Day 1 | 0.07 scores on a scale | Standard Deviation 0.234 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 21 Day 1 | 0.08 scores on a scale | Standard Deviation 0.268 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 5 Day 1 | 0.02 scores on a scale | Standard Deviation 0.21 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 24 Day 1 | 0.07 scores on a scale | Standard Deviation 0.272 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 9 Day 1 | 0.07 scores on a scale | Standard Deviation 0.228 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 27 Day 1 | 0.06 scores on a scale | Standard Deviation 0.299 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 4 Day 1 | 0.04 scores on a scale | Standard Deviation 0.196 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 30 Day 1 | 0.05 scores on a scale | Standard Deviation 0.261 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 12 Day 1 | 0.07 scores on a scale | Standard Deviation 0.187 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 33 Day 1 | 0.00 scores on a scale | Standard Deviation 0.282 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 6 Day 1 | 0.05 scores on a scale | Standard Deviation 0.23 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 36 Day 1 | 0.06 scores on a scale | Standard Deviation 0.231 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 15 Day 1 | 0.07 scores on a scale | Standard Deviation 0.25 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 39 Day 1 | 0.06 scores on a scale | Standard Deviation 0.255 |
| Ruxolitinib | Change From Baseline in EQ-5D-5L | Cycle 2 Day 1 | 0.03 scores on a scale | Standard Deviation 0.214 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 39 Day 1 | 0.01 scores on a scale | Standard Deviation 0.214 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 2 Day 1 | -0.01 scores on a scale | Standard Deviation 0.163 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 3 Day 1 | -0.04 scores on a scale | Standard Deviation 0.259 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 4 Day 1 | -0.01 scores on a scale | Standard Deviation 0.192 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 5 Day 1 | -0.03 scores on a scale | Standard Deviation 0.243 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 6 Day 1 | 0.01 scores on a scale | Standard Deviation 0.186 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 7 Day 1 | -0.00 scores on a scale | Standard Deviation 0.225 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 9 Day 1 | -0.02 scores on a scale | Standard Deviation 0.166 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 12 Day 1 | 0.02 scores on a scale | Standard Deviation 0.158 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 15 Day 1 | 0.03 scores on a scale | Standard Deviation 0.14 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 18 Day 1 | 0.02 scores on a scale | Standard Deviation 0.11 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 21 Day 1 | -0.00 scores on a scale | Standard Deviation 0.222 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 24 Day 1 | 0.01 scores on a scale | Standard Deviation 0.164 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 27 Day 1 | 0.03 scores on a scale | Standard Deviation 0.182 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 30 Day 1 | 0.01 scores on a scale | Standard Deviation 0.159 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 33 Day 1 | 0.05 scores on a scale | Standard Deviation 0.186 |
| Best Available Therapy | Change From Baseline in EQ-5D-5L | Cycle 36 Day 1 | 0.04 scores on a scale | Standard Deviation 0.216 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The FACT-BMT is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family, and emotional well-being, together with additional concerns relevant for bone marrow transplantation participants. The questions were based on a 5-point Likert scale, where 0 corresponds to not at all and 4 corresponds to very much. The higher the final score, the better the quality of life. The FACT-BMT total score ranges from 0 to 148.
Time frame: Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)
Population: FAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 21 Day 1 | 5.24 scores on a scale | Standard Deviation 19.485 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 33 Day 1 | 5.17 scores on a scale | Standard Deviation 20.33 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 2 Day 1 | 2.32 scores on a scale | Standard Deviation 12.191 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 3 Day 1 | 0.62 scores on a scale | Standard Deviation 14.452 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 4 Day 1 | 1.98 scores on a scale | Standard Deviation 15.888 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 5 Day 1 | 1.25 scores on a scale | Standard Deviation 14.577 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 6 Day 1 | 2.91 scores on a scale | Standard Deviation 14.562 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 7 Day 1 | 4.14 scores on a scale | Standard Deviation 14.669 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 9 Day 1 | 5.32 scores on a scale | Standard Deviation 16.815 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 12 Day 1 | 7.26 scores on a scale | Standard Deviation 19.296 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 15 Day 1 | 5.07 scores on a scale | Standard Deviation 18.22 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 18 Day 1 | 4.10 scores on a scale | Standard Deviation 19.44 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 24 Day 1 | 5.90 scores on a scale | Standard Deviation 19.662 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 27 Day 1 | 6.23 scores on a scale | Standard Deviation 18.88 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 30 Day 1 | 7.53 scores on a scale | Standard Deviation 20.314 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 36 Day 1 | 8.72 scores on a scale | Standard Deviation 18.71 |
| Ruxolitinib | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 39 Day 1 | 8.65 scores on a scale | Standard Deviation 21.669 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 27 Day 1 | 5.10 scores on a scale | Standard Deviation 18.885 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 21 Day 1 | 3.68 scores on a scale | Standard Deviation 17.378 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 12 Day 1 | 3.74 scores on a scale | Standard Deviation 18.059 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 36 Day 1 | 4.77 scores on a scale | Standard Deviation 24.186 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 2 Day 1 | -0.22 scores on a scale | Standard Deviation 14.949 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 15 Day 1 | 7.58 scores on a scale | Standard Deviation 17.063 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 3 Day 1 | -1.82 scores on a scale | Standard Deviation 15.849 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 30 Day 1 | 5.75 scores on a scale | Standard Deviation 21.037 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 4 Day 1 | -1.05 scores on a scale | Standard Deviation 16.147 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 18 Day 1 | 8.19 scores on a scale | Standard Deviation 17.993 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 5 Day 1 | -0.23 scores on a scale | Standard Deviation 18.903 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 33 Day 1 | 5.67 scores on a scale | Standard Deviation 22.573 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 6 Day 1 | 2.41 scores on a scale | Standard Deviation 14.766 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 24 Day 1 | 7.84 scores on a scale | Standard Deviation 18.561 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 7 Day 1 | 0.85 scores on a scale | Standard Deviation 16.811 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 39 Day 1 | 6.64 scores on a scale | Standard Deviation 22.384 |
| Best Available Therapy | Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Cycle 9 Day 1 | 1.20 scores on a scale | Standard Deviation 17.635 |
Secondary
CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
CL/F was defined as the oral dose clearance of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule.
Time frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Population: PAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 1 | 15.6 Liters/hour | Geometric Coefficient of Variation 32.7 |
| Ruxolitinib | CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 15 | 15.2 Liters/hour | Geometric Coefficient of Variation 20.4 |
Secondary
Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
Cmax was defined as the maximum observed plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule.
Time frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Population: Pharmacokinetic Analysis Set (PAS): all participants who provided at least one evaluable pharmacokinetic (PK) concentration. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 1 | 167 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.3 |
| Ruxolitinib | Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 15 | 215 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.8 |
Secondary
Cumulative Incidence of Malignancy Relapse/Recurrence (MR)
Defined as the cumulative incidence rate from competing risk analysis of MR from the date of randomization to hematologic malignancy relapse/recurrence.
Time frame: Months 3, 6, 12, 18, 24, 30, and 36
Population: FAS. Cumulative incidence was calculated for participants with underlying hematologic malignant disease. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 3 to < 6 months | 3.22 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 18 to < 24 months | 8.48 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 6 to < 12 months | 5.18 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 24 to <30 months | 8.48 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 0 to < 3 months | 1.92 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 30 to <36 months | 8.48 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 12 to < 18 months | 7.82 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 30 to <36 months | 7.50 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 0 to < 3 months | 1.31 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 6 to < 12 months | 6.08 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 12 to < 18 months | 6.08 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 18 to < 24 months | 6.08 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 24 to <30 months | 6.78 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) | 3 to < 6 months | 2.65 percentage of participants |
Secondary
Cumulative Incidence of Non-relapse Mortality (NRM)
Defined as the cumulative incidence rate from competing risk analysis for NRM from the date of randomization to the date of death not preceded by underlying disease relapse/recurrence.
Time frame: Months 3, 6, 12, 18, 24, 30, and 36
Population: FAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 12 | 15.30 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 24 | 17.83 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 6 | 9.13 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 30 | 17.83 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 18 | 15.93 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 36 | 17.83 percentage of participants |
| Ruxolitinib | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 3 | 5.45 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 36 | 22.0 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 3 | 4.44 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 6 | 6.43 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 12 | 15.12 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 18 | 16.48 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 24 | 19.22 percentage of participants |
| Best Available Therapy | Cumulative Incidence of Non-relapse Mortality (NRM) | Month 30 | 19.22 percentage of participants |
Secondary
Duration of Response Through Study Completion
DOR was defined as the time from first response until cGvHD progression, death, or the date of change/addition of systemic therapies for cGvHD and as assessed for responders only. Response was based on cGvHD disease assessments (National Institutes of Health consensus criteria). Duration of response was evaluated in participants who achieved a CR or PR at or before Cycle 7 Day 1. The analysis included a larger number of participants than the number of participants who achieved CR or PR at Cycle 7 Day 1 (82 ruxolitinib and 42 BAT) because the analysis took into account not only those participants who achieved CR or PR at Cycle 7 Day 1, but also participants who achieved CR or PR before Cycle 7 Day 1 but who may have lost their response at Cycle 7 Day 1. For this reason, the number of participants in this analysis does not align with the best overall response (BOR) at Cycle 7 Day 1. This analysis was based on the cutoff date upon study completion (December 2022).
Time frame: from first response to LPLV (approximately 5 years)
Population: FAS. Duration of response was evaluated in participants who achieved a CR or PR at or before Cycle 7 Day 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Duration of Response Through Study Completion | NA Months |
| Best Available Therapy | Duration of Response Through Study Completion | 6.4 Months |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Adverse events were defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occurred after the participant's signed informed consent was obtained. Abnormal laboratory values or test results occurring after informed consent constituted adverse events only if they induced clinical signs or symptoms, were considered clinically significant, required therapy (e.g., hematologic abnormality that required transfusion or hematological stem cell support), or required changes in study medication(s). TEAEs were defined as those AEs that started or worsened during the on-treatment period (either randomized or cross-over period).
Time frame: from Baseline to LPLV (approximately 5 years)
Population: Safety Set. Six participants in the BAT arm discontinued before receiving the first dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ruxolitinib | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 165 Participants |
| Best Available Therapy | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 148 Participants |
| Ruxolitinib Cross-Over Period | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 70 Participants |
Secondary
ORR at the End of Cycle 3
ORR was defined as the percentage of participants in each arm demonstrating a CR or PR based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.
Time frame: Cycle 4 Day 1 (each cycle was comprised of 4 weeks)
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | ORR at the End of Cycle 3 | 54.5 percentage of participants |
| Best Available Therapy | ORR at the End of Cycle 3 | 31.1 percentage of participants |
p-value: <0.000195% CI: [1.75, 4.39]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
Time frame: from the date of randomization to the date of death due to any cause up to LPLV (approximately 5 years)
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Overall Survival (OS) | NA months |
| Best Available Therapy | Overall Survival (OS) | NA months |
p-value: 0.239695% CI: [0.544, 1.331]Log Rank
Secondary
Percentage of Participants Successfully Tapered Off of All Corticosteroids
All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants who successfully tapered off of all corticosteroids. Participants who completely tapered off corticosteroids refer to those who permanently discontinued steroids as per the dose administration panel and who did not restart steroids in the same interval. Participants who were tapered off and continued follow-up were also counted as being tapered off with 0 dose in subsequent intervals until they discontinued from the main treatment period or restarted steroid treatment.
Time frame: up to Day 179
Population: FAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 57 to ≤ Day 84 | 14.0 percentage of participants |
| Ruxolitinib | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 113 to ≤ Day 140 | 19.7 percentage of participants |
| Ruxolitinib | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 29 to ≤ Day 56 | 9.6 percentage of participants |
| Ruxolitinib | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 141 to ≤ Day 168 | 24.2 percentage of participants |
| Ruxolitinib | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 85 to ≤ Day 112 | 16.3 percentage of participants |
| Ruxolitinib | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 169 to ≤ Day 179 | 24.1 percentage of participants |
| Ruxolitinib | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 1 to ≤ Day 28 | 2.5 percentage of participants |
| Best Available Therapy | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 169 to ≤ Day 179 | 15.9 percentage of participants |
| Best Available Therapy | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 1 to ≤ Day 28 | 2.6 percentage of participants |
| Best Available Therapy | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 29 to ≤ Day 56 | 5.4 percentage of participants |
| Best Available Therapy | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 57 to ≤ Day 84 | 8.5 percentage of participants |
| Best Available Therapy | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 85 to ≤ Day 112 | 10.3 percentage of participants |
| Best Available Therapy | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 113 to ≤ Day 140 | 12.4 percentage of participants |
| Best Available Therapy | Percentage of Participants Successfully Tapered Off of All Corticosteroids | Day 141 to ≤ Day 168 | 16.8 percentage of participants |
Secondary
Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose
All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants with a ≥ 50% reduction in daily corticosteroid dose.
Time frame: from Day 15 up to Day 182
Population: Safety Set: all participants who received at least one dose of study treatment. Participants were to have been analyzed according to the study treatment received, where treatment received was defined as the randomized treatment if the participant took at least one dose of that treatment or the first treatment received if the randomized treatment was never received. Six participants in the BAT arm discontinued before receiving the first dose. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 15 to ≤ Day 28 | 12.7 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 29 to ≤ Day 42 | 35.0 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 43 to ≤ Day 56 | 48.4 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 57 to ≤ Day 70 | 58.7 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 71 to ≤ Day 84 | 62.3 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 85 to ≤ Day 98 | 69.5 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 99 to ≤ Day 112 | 71.2 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 113 to ≤ Day 126 | 73.2 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 127 to ≤ Day 140 | 72.8 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 141 to ≤ Day 154 | 70.0 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 155 to ≤ Day 168 | 74.6 percentage of participants |
| Ruxolitinib | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 169 to ≤ Day 182 | 81.9 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 155 to ≤ Day 168 | 71.6 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 15 to ≤ Day 28 | 13.2 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 99 to ≤ Day 112 | 60.4 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 29 to ≤ Day 42 | 33.1 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 141 to ≤ Day 154 | 68.3 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 43 to ≤ Day 56 | 41.1 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 113 to ≤ Day 126 | 66.2 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 57 to ≤ Day 70 | 47.9 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 169 to ≤ Day 182 | 88.8 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 71 to ≤ Day 84 | 51.4 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 127 to ≤ Day 140 | 68.3 percentage of participants |
| Best Available Therapy | Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose | Day 85 to ≤ Day 98 | 54.0 percentage of participants |
Secondary
Rate of Failure-free Survival (FFS)
Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD.
Time frame: Baseline to when the last participant reached Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Population: FAS. Data reported are from the start of the study to Cycle 7 Day 1 (data cutoff of 08 May 2020).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Rate of Failure-free Survival (FFS) | NA months |
| Best Available Therapy | Rate of Failure-free Survival (FFS) | 5.7 months |
p-value: <0.000195% CI: [0.268, 0.51]Log Rank
Secondary
Rate of FFS at Study Completion
Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD.
Time frame: From Baseline to Last Participant Last Visit (LPLV) (approximately 5 years)
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Rate of FFS at Study Completion | 38.4 months |
| Best Available Therapy | Rate of FFS at Study Completion | 5.7 months |
95% CI: [0.268, 0.485]
Secondary
Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score
To assess improvement of symptoms based on the total symptom score (TSS); a responder was defined as having achieved a clinically relevant reduction from Baseline of the TSS. The scale consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy, and psychological). Participants reported their level of symptom bother over the previous month on a 5-point likert scale: not at all, slightly, moderately, quite a bit, or extremely. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms.
Time frame: Baseline; Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
Population: FAS. Data reported are from the start of the study to Cycle 7 Day 1 (data cutoff of 08 May 2020).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score | 24.2 percentage of participants |
| Best Available Therapy | Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score | 11.0 percentage of participants |
Secondary
t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
t1/2 was defined as the apparent terminal phase disposition half-life of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule.
Time frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Population: PAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 1 | 2.40 hours | Geometric Coefficient of Variation 28.9 |
| Ruxolitinib | t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 15 | 2.32 hours | Geometric Coefficient of Variation 19.8 |
Secondary
Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
tmax was defined as the time to reach the maximum plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule.
Time frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Population: PAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ruxolitinib | Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 1 | 0.833 hours |
| Ruxolitinib | Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 15 | 1.00 hours |
Secondary
Utilization of Medical Resources
The percentage of participants with at least one submission to healthcare encounter was assessed.
Time frame: from Baseline to LPLV (approximately 5 years)
Population: Safety Set. Six participants in the BAT arm discontinued before receiving the first dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | Utilization of Medical Resources | 57.0 percentage of participants |
| Best Available Therapy | Utilization of Medical Resources | 65.8 percentage of participants |
Secondary
Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
Vz/F was defined as the apparent oral dose volume of distribution of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule.
Time frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose
Population: PAS. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 15 | 50.9 Liters | Geometric Coefficient of Variation 33.9 |
| Ruxolitinib | Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses | Day 1 | 54.0 Liters | Geometric Coefficient of Variation 25 |