Graft vs Host Disease
Conditions
Brief summary
The purpose of this study is to evaluate efficacy of ibrutinib in Japanese participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response \[CR\] and partial response \[PR\] defined by National Institutes of Health \[NIH\] consensus development project criteria \[2014\]).
Interventions
DRUGIbrutinib
Participants will receive 420 mg (3 \* 140 mg capsules) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as modified National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): a) Dependent disease, defined as, when glucocorticoid (prednisolone doses greater than or equal to \[\>=\] 0.25 milligram per kilogram per day (mg/kg/day)or \>=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. In case of inability to taper the dose to less than or equal to (\<=)0.25 mg/kg/day or \<=0.5 mg/kg every other day (prednisolone doses) due to recurrence or progression of cGVHD manifestations, it is considered as steroid-dependent disease if the lowest tapering dose of the second occasion is equal or higher than the lowest tapering dose of the first occasion; b) Refractory disease, defined as, when cGVHD manifestations progress despite the use of a regimen containing glucocorticoid (prednisolone at \>=1 mg/kg/day for at least 1 week) or persist without improvement despite continued treatment with glucocorticoid (prednisolone at \>=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks * Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting ibrutinib * At the time of trial enrollment, participants may be receiving other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting ibrutinib * Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment * Karnofsky or Lansky (participants less than \[\<\]16 years) performance status \>=60
Exclusion criteria
* Active acute graft versus host disease (GVHD) * More than 3 previous systemic treatments for cGVHD. Treatment with glucocorticoids is considered a treatment for cGVHD and should be included in determining the number of previous treatments * History of treatment with a tyrosine kinase inhibitor (example \[e.g.\] imatinib), purine analogs, or other cancer chemotherapy in the 4 weeks prior to starting ibrutinib. Participants may have received ibrutinib pre-transplant for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma * History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib * Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 3 year 6 months | ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death based on the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and chronic graft versus host disease (cGVHD) progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Response Rate | Up to 3 year 6 months | Sustained response rate was defined as percentage of participants with NIH defined CR or PR that was sustained for at least 20 weeks. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site. |
| Duration of Response (DOR) | Up to 3 year 6 months | DOR is defined as the duration from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurred first. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. |
| cGVHD Response Rate at Each Timepoints | Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157 | cGVHD response rate was defined as percentage of participants with NIH defined CR or PR at each timepoint. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site. |
| Change in the Amount of Corticosteroid Required Over Time | Baseline, Weeks 24, 48, 96, and 144 | Change in the amount of corticosteroid required over time was reported. |
| Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score | Up to 3 year 6 months | Percentage of participants with overall improvement in Lee cGVHD symptom scale score was reported. Lee cGVHD symptom scale is a patient-reported symptom scale used to measure symptom burden and has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0-Not at all, 1-Slightly, 2-Moderately, 3-Quite a bit, 4-Extremely, with lower values representing a better outcome. A score was calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 with a higher score indicating worse symptoms. An overall score was calculated as the average of these 7 subscales if at least 4 subscales had valid scores. A change of greater than or equal to (\>=) 7 points on the Lee cGVHD symptom scale overall score was considered significant and relates to improvement in quality of life (QoL). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 3 year 6 months | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are adverse events with onset during the treatment phase or that were a consequence of a preexisting condition that has worsened since baseline, and occurred during treatment or within 30 days following the last dose of study treatment, or any adverse event that was considered study treatment-related regardless of the start date of the event. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib | Day 1 of Weeks 1 and 2 | AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib. |
| Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib | 0 to 24 hours (Day 1 of Weeks 1 and 2) | AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Day 1 of Weeks 1 and 2 | Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib. |
| Elimination Half-Life (t1/2) of Ibrutinib | Day 1 of Weeks 1 and 2 | T1/2 is defined as elimination half-life of ibrutinib. |
| Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Day 1 of Weeks 1 and 2 | Cmax is defined as maximum observed plasma concentration of ibrutinib. |
| Apparent Volume of Distribution (Vd/F) of Ibrutinib | Day 1 of Weeks 1 and 2 | Vd/F is defined as apparent volume of distribution of ibrutinib. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib | Day 1 of Weeks 1 and 2 | AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of ibrutinib. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227 | Day 1 of Weeks 1 and 2 | AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of PCI-45227. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227 | 0 to 24 hours (Day 1 of Weeks 1 and 2) | AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of PCI-45227. |
| Maximum Observed Plasma Concentration (Cmax) of PCI-45227 | Day 1 of Weeks 1 and 2 | Cmax is defined as maximum observed plasma concentration of PCI-45227. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 | Day 1 of Weeks 1 and 2 | Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227. |
| Elimination Half-Life (t1/2) of PCI-45227 | Day 1 of Weeks 1 and 2 | T1/2 is defined as elimination half-life of PCI-45227. |
| Apparent Clearance (CL/F) of PCI-45227 | Day 1 of Weeks 1 and 2 | CL/F is defined as apparent clearance of PCI-45227. |
| Apparent Volume of Distribution (Vd/F) of PCI-45227 | Day 1 of Weeks 1 and 2 | Vd/F is defined as apparent volume of distribution of PCI-45227. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227 | Day 1 of Weeks 1 and 2 | AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of PCI-45227. |
| Apparent Clearance (CL/F) of Ibrutinib | Day 1 of Weeks 1 and 2 | CL/F is defined as apparent clearance of ibrutinib. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibrutinib 420 mg Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 7 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Ibrutinib 420 mg |
|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 16.24 |
| Age, Customized From 18 to 64 years | 18 Participants |
| Age, Customized Less Than or Equal to 17 years (adolescent) | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment JAPAN | 19 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 19 |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 12 / 19 |
Outcome results
Primary
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death based on the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and chronic graft versus host disease (cGVHD) progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Time frame: Up to 3 year 6 months
Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibrutinib 420 mg | Overall Response Rate (ORR) | 84.2 Percentage of participants |
Secondary
Apparent Clearance (CL/F) of Ibrutinib
CL/F is defined as apparent clearance of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Apparent Clearance (CL/F) of Ibrutinib | Week 1: Day 1 | 194211 Milliliters per hour (mL/h) | Standard Deviation 106164 |
| Ibrutinib 420 mg | Apparent Clearance (CL/F) of Ibrutinib | Week 2: Day 1 | 162457 Milliliters per hour (mL/h) | Standard Deviation 31966 |
Secondary
Apparent Clearance (CL/F) of PCI-45227
CL/F is defined as apparent clearance of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Apparent Clearance (CL/F) of PCI-45227 | Week 1: Day 1 | 251681 mL/h | Standard Deviation 68392 |
| Ibrutinib 420 mg | Apparent Clearance (CL/F) of PCI-45227 | Week 2: Day 1 | 111922 mL/h | — |
Secondary
Apparent Volume of Distribution (Vd/F) of Ibrutinib
Vd/F is defined as apparent volume of distribution of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Apparent Volume of Distribution (Vd/F) of Ibrutinib | Week 1: Day 1 | 1350160 Milliliters (mL) | Standard Deviation 748511 |
Secondary
Apparent Volume of Distribution (Vd/F) of PCI-45227
Vd/F is defined as apparent volume of distribution of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Apparent Volume of Distribution (Vd/F) of PCI-45227 | Week 1: Day 1 | 2148283 mL | Standard Deviation 653626 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib.
Time frame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib | Week 1: Day 1 | 2929.3 hour*ng/mL | Standard Deviation 1797.4 |
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib | Week 2: Day 1 | 4035.6 hour*ng/mL | Standard Deviation 4277.2 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227
AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of PCI-45227.
Time frame: 0 to 24 hours (Day 1 of Weeks 1 and 2)
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227 | Week 1: Day 1 | 1803.0 hour*ng/mL | Standard Deviation 585.84 |
| Ibrutinib 420 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227 | Week 2: Day 1 | 2547.6 hour*ng/mL | Standard Deviation 999 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib | Week 1: Day 1 | 2643.8 hour*ng/mL | Standard Deviation 1656.2 |
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib | Week 2: Day 1 | 2659.2 hour*ng/mL | Standard Deviation 506.57 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227
AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227 | Week 1: Day 1 | 1766.1 hour*ng/mL | Standard Deviation 478.74 |
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227 | Week 2: Day 1 | 3752.6 hour*ng/mL | — |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib
AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Population: The pharmacokinetic (PK) evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib | Week 1: Day 1 | 3683.7 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 3146.9 |
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib | Week 2: Day 1 | 4024.8 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 4287.2 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227
AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227 | Week 1: Day 1 | 1976.9 h*ng/mL | Standard Deviation 968.83 |
| Ibrutinib 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227 | Week 2: Day 1 | 2547.6 h*ng/mL | Standard Deviation 999 |
Secondary
cGVHD Response Rate at Each Timepoints
cGVHD response rate was defined as percentage of participants with NIH defined CR or PR at each timepoint. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Time frame: Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157
Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 5 | 26.3 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 13 | 42.1 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 25 | 52.6 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 37 | 47.4 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 49 | 47.4 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 61 | 42.1 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 73 | 36.8 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 85 | 31.6 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 97 | 31.6 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 109 | 31.6 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 121 | 36.8 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 133 | 31.6 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 145 | 26.3 Percentage of participants |
| Ibrutinib 420 mg | cGVHD Response Rate at Each Timepoints | Week 157 | 10.5 Percentage of participants |
Secondary
Change in the Amount of Corticosteroid Required Over Time
Change in the amount of corticosteroid required over time was reported.
Time frame: Baseline, Weeks 24, 48, 96, and 144
Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug. Here, 'n' (number analyzed) represents number of participants evaluable at the specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ibrutinib 420 mg | Change in the Amount of Corticosteroid Required Over Time | Baseline | 0.270 Milligrams per kilograms per day |
| Ibrutinib 420 mg | Change in the Amount of Corticosteroid Required Over Time | Week 24 | 0.250 Milligrams per kilograms per day |
| Ibrutinib 420 mg | Change in the Amount of Corticosteroid Required Over Time | Week 48 | 0.150 Milligrams per kilograms per day |
| Ibrutinib 420 mg | Change in the Amount of Corticosteroid Required Over Time | Week 96 | 0.140 Milligrams per kilograms per day |
| Ibrutinib 420 mg | Change in the Amount of Corticosteroid Required Over Time | Week 144 | 0.140 Milligrams per kilograms per day |
Secondary
Duration of Response (DOR)
DOR is defined as the duration from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurred first. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Time frame: Up to 3 year 6 months
Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug and achieved PR or better response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibrutinib 420 mg | Duration of Response (DOR) | NA Months |
Secondary
Elimination Half-Life (t1/2) of Ibrutinib
T1/2 is defined as elimination half-life of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ibrutinib 420 mg | Elimination Half-Life (t1/2) of Ibrutinib | Week 1: Day 1 | 4.9 Hours |
| Ibrutinib 420 mg | Elimination Half-Life (t1/2) of Ibrutinib | Week 2: Day 1 | 4.4 Hours |
Secondary
Elimination Half-Life (t1/2) of PCI-45227
T1/2 is defined as elimination half-life of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set is defined as all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ibrutinib 420 mg | Elimination Half-Life (t1/2) of PCI-45227 | Week 1: Day 1 | 5.9 Hours |
| Ibrutinib 420 mg | Elimination Half-Life (t1/2) of PCI-45227 | Week 2: Day 1 | 5.4 Hours |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Cmax is defined as maximum observed plasma concentration of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Week 1: Day 1 | 490.45 Nanograms per milliliter (ng/mL) | Standard Deviation 366.07 |
| Ibrutinib 420 mg | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Week 2: Day 1 | 478.01 Nanograms per milliliter (ng/mL) | Standard Deviation 508.08 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PCI-45227
Cmax is defined as maximum observed plasma concentration of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibrutinib 420 mg | Maximum Observed Plasma Concentration (Cmax) of PCI-45227 | Week 1: Day 1 | 185.37 ng/mL | Standard Deviation 91.874 |
| Ibrutinib 420 mg | Maximum Observed Plasma Concentration (Cmax) of PCI-45227 | Week 2: Day 1 | 203.16 ng/mL | Standard Deviation 82.292 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are adverse events with onset during the treatment phase or that were a consequence of a preexisting condition that has worsened since baseline, and occurred during treatment or within 30 days following the last dose of study treatment, or any adverse event that was considered study treatment-related regardless of the start date of the event.
Time frame: Up to 3 year 6 months
Population: The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibrutinib 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 19 Participants |
Secondary
Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score
Percentage of participants with overall improvement in Lee cGVHD symptom scale score was reported. Lee cGVHD symptom scale is a patient-reported symptom scale used to measure symptom burden and has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0-Not at all, 1-Slightly, 2-Moderately, 3-Quite a bit, 4-Extremely, with lower values representing a better outcome. A score was calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 with a higher score indicating worse symptoms. An overall score was calculated as the average of these 7 subscales if at least 4 subscales had valid scores. A change of greater than or equal to (\>=) 7 points on the Lee cGVHD symptom scale overall score was considered significant and relates to improvement in quality of life (QoL).
Time frame: Up to 3 year 6 months
Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibrutinib 420 mg | Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score | 52.6 Percentage of participants |
Secondary
Sustained Response Rate
Sustained response rate was defined as percentage of participants with NIH defined CR or PR that was sustained for at least 20 weeks. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
Time frame: Up to 3 year 6 months
Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug and achieved PR or better response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibrutinib 420 mg | Sustained Response Rate | 68.8 Percentage of participants |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ibrutinib 420 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Week 1: Day 1 | 3.87 Hours |
| Ibrutinib 420 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Week 2: Day 1 | 4.02 Hours |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227
Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227.
Time frame: Day 1 of Weeks 1 and 2
Population: The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ibrutinib 420 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 | Week 1: Day 1 | 4.00 Hours |
| Ibrutinib 420 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 | Week 2: Day 1 | 4.02 Hours |