Trial Outcomes & Findings for A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD) (NCT NCT03474679)

Last Updated: 2025-02-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

19 participants

Primary outcome timeframe

Up to 3 year 6 months

Results posted on

2025-02-04

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	19
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Death	7
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibrutinib 420 mg n=19 Participants 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.
Age, Continuous	40.5 years STANDARD_DEVIATION 16.24 • n=5 Participants
Age, Customized Less Than or Equal to 17 years (adolescent)	1 Participants n=5 Participants
Age, Customized From 18 to 64 years	18 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	19 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment JAPAN	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 year 6 months

Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Overall Response Rate (ORR)	84.2 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=16 Participants 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.
Sustained Response Rate	68.8 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=16 Participants 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.
Duration of Response (DOR)	NA Months Interval 5.3 to Here, 'NA' indicates that median and upper limit of 95% confidence interval were not estimable due to the less number of events.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
cGVHD Response Rate at Each Timepoints Week 5	26.3 Percentage of participants Interval 9.1 to 51.2
cGVHD Response Rate at Each Timepoints Week 13	42.1 Percentage of participants Interval 20.3 to 66.5
cGVHD Response Rate at Each Timepoints Week 25	52.6 Percentage of participants Interval 28.9 to 75.6
cGVHD Response Rate at Each Timepoints Week 37	47.4 Percentage of participants Interval 24.4 to 71.1
cGVHD Response Rate at Each Timepoints Week 49	47.4 Percentage of participants Interval 24.4 to 71.1
cGVHD Response Rate at Each Timepoints Week 61	42.1 Percentage of participants Interval 20.3 to 66.5
cGVHD Response Rate at Each Timepoints Week 73	36.8 Percentage of participants Interval 16.3 to 61.6
cGVHD Response Rate at Each Timepoints Week 85	31.6 Percentage of participants Interval 12.6 to 56.6
cGVHD Response Rate at Each Timepoints Week 97	31.6 Percentage of participants Interval 12.6 to 56.6
cGVHD Response Rate at Each Timepoints Week 109	31.6 Percentage of participants Interval 12.6 to 56.6
cGVHD Response Rate at Each Timepoints Week 121	36.8 Percentage of participants Interval 16.3 to 61.6
cGVHD Response Rate at Each Timepoints Week 133	31.6 Percentage of participants Interval 12.6 to 56.6
cGVHD Response Rate at Each Timepoints Week 145	26.3 Percentage of participants Interval 9.1 to 51.2
cGVHD Response Rate at Each Timepoints Week 157	10.5 Percentage of participants Interval 1.3 to 33.1

SECONDARY outcome

Timeframe: 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.

Change in the amount of corticosteroid required over time was reported.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Change in the Amount of Corticosteroid Required Over Time Baseline	0.270 Milligrams per kilograms per day Interval 0.08 to 1.77
Change in the Amount of Corticosteroid Required Over Time Week 24	0.250 Milligrams per kilograms per day Interval 0.08 to 0.87
Change in the Amount of Corticosteroid Required Over Time Week 48	0.150 Milligrams per kilograms per day Interval 0.06 to 0.64
Change in the Amount of Corticosteroid Required Over Time Week 96	0.140 Milligrams per kilograms per day Interval 0.01 to 0.59
Change in the Amount of Corticosteroid Required Over Time Week 144	0.140 Milligrams per kilograms per day Interval 0.05 to 0.56

SECONDARY outcome

Timeframe: Up to 3 year 6 months

Population: All treated analysis set included all enrolled participants who received at least 1 dose of study drug.

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).

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score	52.6 Percentage of participants Interval 28.9 to 75.6

SECONDARY outcome

Timeframe: Up to 3 year 6 months

Population: The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	19 Participants

SECONDARY outcome

Timeframe: 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.

AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
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 hoursnanograms per milliliter (hng/mL) Standard Deviation 3146.9
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 hoursnanograms per milliliter (hng/mL) Standard Deviation 4287.2

SECONDARY outcome

Timeframe: 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.

AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
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
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 outcome

Timeframe: 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.

Cmax is defined as maximum observed plasma concentration of ibrutinib.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib Week 1: Day 1	490.45 Nanograms per milliliter (ng/mL) Standard Deviation 366.07
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib Week 2: Day 1	478.01 Nanograms per milliliter (ng/mL) Standard Deviation 508.08

SECONDARY outcome

Timeframe: 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.

Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib Week 1: Day 1	3.87 Hours Interval 1.78 to 5.75
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib Week 2: Day 1	4.02 Hours Interval 1.75 to 5.43

SECONDARY outcome

Timeframe: 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.

T1/2 is defined as elimination half-life of ibrutinib.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
Elimination Half-Life (t1/2) of Ibrutinib Week 1: Day 1	4.9 Hours Interval 4.4 to 5.2
Elimination Half-Life (t1/2) of Ibrutinib Week 2: Day 1	4.4 Hours Interval 3.8 to 10.2

SECONDARY outcome

Timeframe: Day 1 of Weeks 1 and 2

CL/F is defined as apparent clearance of ibrutinib.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
Apparent Clearance (CL/F) of Ibrutinib Week 1: Day 1	194211 Milliliters per hour (mL/h) Standard Deviation 106164
Apparent Clearance (CL/F) of Ibrutinib Week 2: Day 1	162457 Milliliters per hour (mL/h) Standard Deviation 31966

SECONDARY outcome

Timeframe: 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.

Vd/F is defined as apparent volume of distribution of ibrutinib.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
Apparent Volume of Distribution (Vd/F) of Ibrutinib Week 1: Day 1	1350160 Milliliters (mL) Standard Deviation 748511

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
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
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 999.00

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
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
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 999.00

SECONDARY outcome

Timeframe: 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.

Cmax is defined as maximum observed plasma concentration of PCI-45227.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Maximum Observed Plasma Concentration (Cmax) of PCI-45227 Week 1: Day 1	185.37 ng/mL Standard Deviation 91.874
Maximum Observed Plasma Concentration (Cmax) of PCI-45227 Week 2: Day 1	203.16 ng/mL Standard Deviation 82.292

SECONDARY outcome

Timeframe: 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.

Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=19 Participants 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.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 Week 1: Day 1	4.00 Hours Interval 1.88 to 6.18
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 Week 2: Day 1	4.02 Hours Interval 0.0 to 5.28

SECONDARY outcome

Timeframe: 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.

T1/2 is defined as elimination half-life of PCI-45227.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
Elimination Half-Life (t1/2) of PCI-45227 Week 1: Day 1	5.9 Hours Interval 5.2 to 6.5
Elimination Half-Life (t1/2) of PCI-45227 Week 2: Day 1	5.4 Hours Interval 5.4 to 5.4

SECONDARY outcome

Timeframe: Day 1 of Weeks 1 and 2

CL/F is defined as apparent clearance of PCI-45227.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
Apparent Clearance (CL/F) of PCI-45227 Week 1: Day 1	251681 mL/h Standard Deviation 68392
Apparent Clearance (CL/F) of PCI-45227 Week 2: Day 1	111922 mL/h Standard Deviation NA Here, 'NA' indicates that standard deviation could not be calculated for a single participant.

SECONDARY outcome

Timeframe: Day 1 of Weeks 1 and 2

Vd/F is defined as apparent volume of distribution of PCI-45227.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
Apparent Volume of Distribution (Vd/F) of PCI-45227 Week 1: Day 1	2148283 mL Standard Deviation 653626

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ibrutinib 420 mg n=4 Participants 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.
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
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 Standard Deviation NA Here, 'NA' indicates that standard deviation could not be calculated for a single participant.

Adverse Events

Ibrutinib 420 mg

Serious events: 12 serious events

Other events: 19 other events

Deaths: 7 deaths

Serious adverse events

Serious adverse events
Measure	Ibrutinib 420 mg n=19 participants at risk 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.
Blood and lymphatic system disorders Immune Thrombocytopenia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders Atrial Flutter	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Cataract	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal Haemorrhage	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Multiple Organ Dysfunction Syndrome	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Hepatobiliary disorders Liver Disorder	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Immune system disorders Anaphylactic Reaction	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Appendiceal Abscess	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Bronchiolitis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Covid-19	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	36.8% 7/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Bacterial	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Fungal	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Septic Shock	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Atypical Femur Fracture	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Diabetes Mellitus	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Subarachnoid Haemorrhage	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Impairment	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Ibrutinib 420 mg n=19 participants at risk 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.
Blood and lymphatic system disorders Anaemia	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Immune Thrombocytopenia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Increased Tendency to Bruise	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Iron Deficiency Anaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukopenia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Splenic Infarction	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure Chronic	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Endocrine disorders Hypothyroidism	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Cataract	21.1% 4/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Conjunctival Erosion	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Conjunctival Hyperaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Dry Eye	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Glaucoma	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Ocular Hypertension	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Eye disorders Photophobia	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Pain Upper	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ascites	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Cheilitis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	21.1% 4/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dental Caries	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Enterocolitis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastric Haemorrhage	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastric Mucosal Hypertrophy	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal Haemorrhage	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	26.3% 5/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Stomatitis	47.4% 9/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Tooth Loss	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Generalised Oedema	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Malaise	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Oedema Peripheral	21.1% 4/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Physical Deconditioning	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Pyrexia	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic Function Abnormal	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Hepatobiliary disorders Liver Disorder	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Immune system disorders Food Allergy	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Immune system disorders Hypogammaglobulinaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Immune system disorders Seasonal Allergy	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Appendiceal Abscess	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Bronchiolitis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	31.6% 6/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Conjunctivitis	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Cytomegalovirus Infection	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Haematoma Infection	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Herpes Zoster	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Impetigo	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Influenza	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Oral Candidiasis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Otitis Externa	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Paronychia	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pharyngitis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	26.3% 5/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Aspiration	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Bacterial	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia Fungal	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Postoperative Wound Infection	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pseudomembranous Colitis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Sinusitis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Upper Respiratory Tract Infection	31.6% 6/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Anaemia Postoperative	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Atypical Femur Fracture	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Bone Contusion	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Joint Injury	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural Pain	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Skin Abrasion	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Skin Laceration	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Tooth Fracture	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Traumatic Haemorrhage	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Alanine Aminotransferase Increased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Amylase Increased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Aspergillus Test Positive	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Blood Beta-D-Glucan Increased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Blood Creatinine Increased	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Blood Fibrinogen Decreased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Blood Lactate Dehydrogenase Increased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Gamma-Glutamyltransferase Increased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Haemoglobin Decreased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Lipase Increased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Lymphocyte Count Decreased	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Neutrophil Count Decreased	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Platelet Count Decreased	31.6% 6/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Weight Decreased	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Investigations Weight Increased	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased Appetite	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypertriglyceridaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Lipid Metabolism Disorder	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Zinc Deficiency	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Immobilisation Syndrome	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Metatarsalgia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle Spasms	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis of Jaw	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoporosis	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute Lymphocytic Leukaemia Recurrent	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pyogenic Granuloma	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Headache	21.1% 4/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Hypoaesthesia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Intercostal Neuralgia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Restless Legs Syndrome	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Toxic Encephalopathy	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Psychiatric disorders Anxiety	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Psychiatric disorders Depression	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Renal and urinary disorders Chronic Kidney Disease	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Renal and urinary disorders Haematuria	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary Retention	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Acne	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dermal Cyst	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis Acneiform	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Drug Eruption	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dry Skin	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Eczema	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Haemorrhage Subcutaneous	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Ingrowing Nail	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	21.1% 4/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Purpura	21.1% 4/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin Atrophy	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin Exfoliation	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin Induration	10.5% 2/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin Ulcer	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Toxic Skin Eruption	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders Haematoma	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	15.8% 3/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	5.3% 1/19 • Up to 3 year 6 months The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Additional Information

EXECUTIVE MEDICAL DIRECTOR

Janssen Pharmaceutical K.K.

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER