Graft vs Host Disease
Conditions
Keywords
cGVHD, Allogeneic hematopoietic stem cell transplantation, Immune System Diseases, Steroid refractory chronic graft vs host disease (cGVHD), Bone Marrow Transplantation, Anti-Inflammatory Agents, Glucocorticoids, Corticosteroids
Brief summary
This study was been conducted to evaluate the safety, tolerability, and activity of belumosudil (formerly known as KD025) in adult participants with chronic graft versus host disease (cGVHD).
Detailed description
Fifty four (54) participants were enrolled to receive orally administered belumosudil 200 milligrams (mg) once daily (QD), belumosudil 200 mg twice daily (BID), or belumosudil 400 mg QD. Study drug was administered in 28-day cycles until disease progression or occurrence of unacceptable toxicity. Participants received study drug in the inpatient or outpatient setting.
Interventions
Pharmaceutical form: Capsules or Tablets Route of administration: Oral
Sponsors
Kadmon, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult male and female participants at least 18 years of age who had allogenic bone marrow transplant (BMT) or hematopoietic stem cell transplantation (HSCT). * Received glucocorticoid therapy and calcineurin therapy or glucocorticoid therapy alone for cGVHD at study entry. Participants on calcineurin therapy only, without glucocorticoid therapy, were not eligible. Participants also received other therapies thought not to be immunosuppressive (such as extracorporeal photopheresis; ECP), were considered for enrollment in this study on a case-by-case basis. * Had persistent active cGVHD manifestations, as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD, after at least 2 months of steroid therapy. * No more than 3 prior lines of treatment for cGVHD. * Karnofsky Performance Scale of greater than (\>) 40. * Adequate organ and bone marrow functions evaluated during the 14 days prior to enrollment as follows: * Absolute neutrophil count greater than or equal to (\>=) 1.5\*10\^9/L (without myeloid growth factors within 1 week of study entry) * Platelet count \>=50\*10\^9/L (without transfusion or thrombopoietin or thrombopoietin analogues within 2 weeks of study entry) * Adequate safety laboratory values: * Total bilirubin less than or equal to (\<=) 1.5\*upper limit of normal (ULN) * Alanine aminotransferase and aspartate aminotransferase \<=3\*ULN * Glomerular filtration rate (GFR) \>= 30 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) using the 4-Variable Modification of Diet in Renal Disease variable formula * Female participants of childbearing potential have a negative pregnancy test at screening. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had any evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, anti estrogens, or ovarian suppression. * Women of childbearing potential (i.e., menstruating women) must had a negative urine pregnancy test (positive urine tests were to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug. * Sexually active women of childbearing potential enrolled in the study must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes: * Intrauterine device plus one barrier method; * Stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; * 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or * A vasectomized partner * For male participants who were sexually active and who were partners of premenopausal women: agreement to use two forms of contraception as in criterion 10 above during the treatment period and for at least 3 months after the last dose of study drug. * Able to provide written informed consent prior to the performance of any study-specific procedures.
Exclusion criteria
* Female participant who was pregnant or breastfeeding. * Received an investigational GVHD treatment within 28 days of study entry. * Had acute GVHD. * Taken any medication known to be a moderate or strong inhibitor of the cytochrome (CY) CYP3A4 isozyme or any drugs that are moderate or strong CYP3A4 inducers. * History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease or coronary artery disease). * Regular and excessive use of alcohol within the 6 months prior to study entry defined as alcohol intake \>14 drinks per week in a man or \>7 drinks per week in a woman. Approximately 10 grams of alcohol equals one drink unit. One unit equals 1 ounce of distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine. * Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV). * Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of enrollment, with the exception of completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection. * Relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening. * Had previous exposure to belumosudil or known allergy/sensitivity to belumosudil or any other Rho-associated protein kinase-2 inhibitor. * Taken other immunosuppressant drugs for GVHD, including mammalian target of rapamycin inhibitors (Note: Only steroids, calcineurin inhibitors, and ECP are acceptable). * Corrected QT interval using Fridericia's formula \>450 milliseconds. * Female participant who was pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response (OR) | From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months) | OR was defined as the percentage of participants with complete response (CR) or partial response (PR). The OR determination of chronic graft versus host disease (cGVHD) was based on cGVHD response assessment performed by clinicians as per the 2014 National Institutes of Health (NIH) Consensus Development Project for Clinical Trials in cGVHD criteria. CR was defined as the resolution of all manifestations in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression was defined as the clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) | From first dose of study drug up to 28 days after the last dose of study drug (maximum duration: up to 64.2 months) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study drug up to 28 days after the last dose of study drug). TEAEs included both SAEs and non-SAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | From Baseline up to end of treatment (i.e., up to 64.2 months) | cGVHD symptom severity was self-reported by participants. Participants were asked to rate their disease symptom severity over the last week on the following questions: skin itching at its worst, moth dryness at its worst, mouth pain at its worst, mouth sensitivity at its worst, main compliant on eyes, symptom severity on eyes. Severity rating was done on a 0 to 10-point numeric rating scare, where score 0 indicated 'not at all severe cGVHD symptoms' and score 10 indicated 'most severe cGVHD symptoms possible'. EOT visit was performed within 3 days after participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. Maximal improvement from Baseline was calculated as the lowest symptom severity score on scheduled visits minus the symptom severity score at Baseline with possible ranges from -10 to 10. The lower the number means the better improvement in cGVHD symptoms. |
| Failure-free Survival (FFS) | From first dose of study drug to either start of another new systemic treatment for cGVHD, relapse of the underlying disease or death or data cut-off, whichever occurred first (maximum duration: up to 64.2 months) | Failure-free survival was defined as the time (in months) from first dose of study drug to either the start of another new systemic treatment for cGVHD, relapse of the underlying disease or death. If no such events happened, FFS was censored by last response assessment or long term follow up assessment, whichever was the latest and available. Kaplan-Meier survival method was used for the analysis. |
| Change From Baseline in Corticosteroids Dose | Baseline up to end of treatment (i.e., anytime up to 64.2 months) | Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug. |
| Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage | Baseline up to end of treatment (i.e., anytime up to 64.2 months) | Calcineurin inhibitors included systemic tacrolimus and cyclosporine. Number of participants who took CNI at Baseline and had reduction and discontinuation in CNI use as compared to Baseline during the study are reported in this outcome measure. EOT visit was performed within 3 days after the participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. |
| Duration of Response (DOR) | From the date of first response until documented disease progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months) | The DOR was defined as the time (in weeks) from first documentation of response to the time of first documentation of deterioration from best response (e.g., CR to PR, or PR to LR). LOR included the response status of unchanged (LOR-U), mixed (LOR-M), or progression (LOR-P). Per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria; CR was defined as the resolution of all manifestations in each organ or site; PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; LOR-M was defined as CR or PR in at least one organ accompanied by progression in another organ, LOR-U was defined as outcomes that did not meet the criteria for CR, PR, progression or mixed response, LOR-P was defined as progression in at least one organ or site without a response in any other organ or site. Kaplan-Meier was used for the analysis. |
| Time-to-Response (TTR) | From first dose of study drug treatment to the time of first documentation of response or data cut-off, whichever occurred first (maximum duration: up to 64.2 months) | Time-to-response was measured as the time (in weeks) from first dose of study drug to the time of first documentation of response. Response was defined as the participants achieving a PR or CR at any post-baseline response assessment. Per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria; CR was defined as the resolution of all manifestations in each organ or site and PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site. |
| Percentage of Participants With Best Response in Each Individual Organ | From date of randomization until disease progression or data cut-off, whichever occurred first (maximum duration: up to 64.2 months) | Best response was defined as the percentage of participants with CR or PR. Response was assessed per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria; CR was defined as the resolution of all manifestations in each organ or site; PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site. Organ response assessment was performed on 9 individual organs: skin, eyes, mouth, esophagus, upper gastrointestinal (GI), lower GI, liver, lungs, and joints and fascia and is reported in this outcome measure. |
| Overall Survival (OS) | From first dose of study drug to date of death from any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months) | Overall survival was defined as the time (in months) from first dose of study drug to the death due to any reason. If there was no death, OS was censored by last visit, last long-term follow-up, or study cut-off date, whichever occurred first. Kaplan-Meier survival method was used for the analysis. |
| Time to Next Therapy (TTNT) | From time of first treatment to the time of new systemic cGVHD treatment or long term follow-up assessment, whichever occurred first (maximum duration: up to 64.2 months) | The TTNT was defined as the time (in months) from first treatment to the time of new systemic cGVHD treatment. TTNT was censored by last response assessment or long term follow up assessment, whichever was earlier. Kaplan-Meier survival method was used for the analysis. |
| Number of Participants With Best Overall Response (BOR) | From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months) | BOR was defined as the participants with either a CR or PR or lack of response (LOR), where LOR included the response status of unchanged (LOR-U), mixed (LOR-M), or progression (LOR-P). BOR was assessed per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria. CR was defined as the resolution of all manifestations in each organ or site; PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; LOR-M was defined as CR or PR in at least one organ accompanied by progression in another organ, LOR-U was defined as outcomes that did not meet the criteria for CR, PR, progression or mixed response, LOR-P was defined as progression in at least one organ or site without a response in any other organ or site. |
| Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Baseline, Day 1 of Cycles 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27, 29,30,31,32,33,34,35,36,37,38, 39,40,41,43, 47,48,49,51,52,53, 54, 55,56, 57,58,60,61,62,63,67, EOT (i.e., anytime up to 64.2 months) | FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug. |
| Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Baseline, Day 1 of Cycles 2, 3,4, 5,6,7,8,9,10,11,12,13, 14,15,16,17,18,19,20,21,22,23,24,25,26, 27,29,30,31,32,33,34,35,36,37,38,39,40,41,43,47, 48,49, 51,52,53,54, 55, 56,57,58,60,61, 62, 63,67, EOT (i.e., anytime up to 64.2 months) | FVC was the total amount of air (in liters) exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug. |
| Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Baseline, Day 1 of Cycles 2,3,4,5,6,7,8,9,10,11,12,13, 14,15,16,17,18,19,20,21,22,23,24,25,26,27, 29,31,32,33,34,35,36,37,39,40,41,43,47,49,51,53,55, 61, 62, 63, 67, EOT (i.e., anytime up to 64.2 Months) | DLco is a measurement of the ability of the lungs to transfer gases from the air to the blood. Change from baseline in diffusing capacity of the lung for carbon monoxide (percent predicted hemoglobin level corrected) was reported for this measure. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug. |
| Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Baseline, Day 1 of Cycles 2,3, 4, 5,6,7, 8, 9, 10,11,12,13, 14, 15, 16, 17, 18, 19, 20,21, 22,23,24, 25, 26, 27,29, 30, 31,32, 33, 34, 35,36, 37, 38,39, 40,41,43,47, 48, 49,51,52,53, 54,55,56,57,58, 60,61,62, 63, 67, EOT (i.e., anytime up to 64.2 Months) | TLC is the volume of air in the lungs upon the maximum effort of inspiration. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug. |
| Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Baseline, Day 1 of Cycles 2, 3, 4,5, 6,7, 8, 9, 10, 11,12, 13, 14,15, 16,17, 18, 19,20, 21,22,23, 24, 25, 26,27, 29, 30, 31, 32, 33,34, 35,36, 37,38, 39, 40,41, 43,47, 48, 49,51,52,53, 54, 55,56,57, 58,60,61,62,63,67, EOT (i.e., anytime up to 64.2 Months) | RV is the volume of air remaining in the lungs after maximum forceful expiration. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug. |
| Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Cycles 1 and 2: pre-dose (0 hour), 1, 2, 3, 4, 5, and 6 hours post-dose on Day 1 | Cmax was the maximum observed plasma concentration, obtained by a non-compartmental analysis. Cmax data for Belumosudil and its metabolites KD025m1 and KD025m2 are reported in this outcome measure. |
| Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Cycles 1 and 2: pre-dose (0 hour), 1, 2, 3, 4, 5, and 6 hours post-dose on Day 1 | Tmax was defined as time to reach maximum observed plasma concentration, obtained by a non-compartmental analysis. Tmax data for Belumosudil and its metabolites KD025m1 and KD025m2 are reported in this outcome measure. |
| Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Cycles 1 and 2: pre-dose (0 hour), 1, 2, 3, 4, 5, and 6 hours post-dose on Day 1 | AUC0-6hr was defined as area under the plasma concentration versus time curve from time 0 to 6 hours post-dose, obtained by a non-compartmental analysis from the concentration-time data. AUC0-6hr data for Belumosudil and its metabolites KD025m1 and KD025m2 are reported in this outcome measure. |
| Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Baseline, Day 1 of Cycles 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26, 27,28,29,30,31,32,33,34,35,36,37, 38,39,40,41,42,43,44,45,46,47,48, 49, 50,51,52,53, 54,55, 56, 57,58,59,60,61,62,63,67 and EOT (i.e., anytime up to 64.2 months) | Lee cGVHD symptom scale, 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 better outcome. Score for each subscale was normalized to a score ranged from 0 to 100, where higher score=worse symptoms. An overall Lee cGvHD score was calculated as average of these 7 subscales and it ranged from 0 to 100, where a higher score = worse symptoms. EOT visit was performed within 3 days after the participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. |
| Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | From Baseline up to end of treatment (i.e., up to 64.2 months) | The GSR assessment was performed by asking the participants to rate their disease severity of cGVHD symptoms on a 0 to 10-point numeric rating scale, where score 0 indicated 'not at all severe cGVHD symptoms' and score 10 indicated 'most severe cGVHD symptoms possible'. The response was defined using scores from 9 organs: skin, eyes, mouth, esophagus, upper gastrointestinal (GI) track, lower GI tract, liver, lungs, and joints and fascia plus GSR. End of treatment (EOT) visit was performed within 3 days after participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. Maximal improvement from Baseline was calculated as lowest GSR score on scheduled visits minus GSR score at Baseline with possible ranges from -10 to 10. The lower the number means the better improvement in cGVHD symptoms. Only those categories in which at least 1 participant had data were reported. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 7 active sites in the United States. A total of 64 participants were screened between 15 September 2016 and 08 March 2018, of which 10 participants were screen failures due to not meeting eligibility criteria.
Pre-assignment details
A total of 54 participants were enrolled and treated with belumosudil in the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Belumosudil 200 mg QD Participants received belumosudil 200 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 64.2 months). | 17 |
| Cohort 2: Belumosudil 200 mg BID Participants received belumosudil 200 mg orally BID in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 45.9 months). | 16 |
| Cohort 3: Belumosudil 400 mg QD Participants received belumosudil 400 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 49.2 months). | 21 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 2 |
| Overall Study | Disease progression | 5 | 11 | 8 |
| Overall Study | Investigator decision | 2 | 0 | 1 |
| Overall Study | Noncompliance to protocol | 1 | 0 | 0 |
| Overall Study | Other | 4 | 1 | 5 |
| Overall Study | Sponsor decision | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 4 |
Baseline characteristics
| Characteristic | Cohort 1: Belumosudil 200 mg QD | Cohort 2: Belumosudil 200 mg BID | Cohort 3: Belumosudil 400 mg QD | Total |
|---|---|---|---|---|
| Age, Continuous | 50.0 years | 55.0 years | 46.0 years | 51.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 15 Participants | 14 Participants | 19 Participants | 48 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 13 Participants | 9 Participants | 12 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 17 | 5 / 16 | 9 / 21 |
| other Total, other adverse events | 17 / 17 | 16 / 16 | 19 / 21 |
| serious Total, serious adverse events | 5 / 17 | 6 / 16 | 13 / 21 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study drug up to 28 days after the last dose of study drug). TEAEs included both SAEs and non-SAEs.
Time frame: From first dose of study drug up to 28 days after the last dose of study drug (maximum duration: up to 64.2 months)
Population: Analysis was performed on safety population which included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 17 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 5 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 16 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 6 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 13 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 20 Participants |
Primary
Percentage of Participants With Overall Response (OR)
OR was defined as the percentage of participants with complete response (CR) or partial response (PR). The OR determination of chronic graft versus host disease (cGVHD) was based on cGVHD response assessment performed by clinicians as per the 2014 National Institutes of Health (NIH) Consensus Development Project for Clinical Trials in cGVHD criteria. CR was defined as the resolution of all manifestations in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression was defined as the clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Time frame: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Overall Response (OR) | 64.7 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Overall Response (OR) | 68.8 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Overall Response (OR) | 57.1 percentage of participants |
Secondary
Change From Baseline in Corticosteroids Dose
Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug.
Time frame: Baseline up to end of treatment (i.e., anytime up to 64.2 months)
Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Corticosteroids Dose | -0.110 milligrams per kilogram per day | Standard Deviation 0.101 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Corticosteroids Dose | -0.111 milligrams per kilogram per day | Standard Deviation 0.147 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Corticosteroids Dose | -0.116 milligrams per kilogram per day | Standard Deviation 0.152 |
Secondary
Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points
Lee cGVHD symptom scale, 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 better outcome. Score for each subscale was normalized to a score ranged from 0 to 100, where higher score=worse symptoms. An overall Lee cGvHD score was calculated as average of these 7 subscales and it ranged from 0 to 100, where a higher score = worse symptoms. EOT visit was performed within 3 days after the participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication.
Time frame: Baseline, Day 1 of Cycles 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26, 27,28,29,30,31,32,33,34,35,36,37, 38,39,40,41,42,43,44,45,46,47,48, 49, 50,51,52,53, 54,55, 56, 57,58,59,60,61,62,63,67 and EOT (i.e., anytime up to 64.2 months)
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. Here, '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 42, Day 1 | 4.6 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 24, Day 1 | -6.7 score on a scale | Standard Deviation 21 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 57, Day 1 | -17.6 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 41, Day 1 | -25.7 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 25, Day 1 | 2.2 score on a scale | Standard Deviation 18.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 11, Day 1 | -3.4 score on a scale | Standard Deviation 11.5 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 40, Day 1 | 2.7 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 26, Day 1 | 1.3 score on a scale | Standard Deviation 14.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 39, Day 1 | -6.2 score on a scale | Standard Deviation 25.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 27, Day 1 | -3.5 score on a scale | Standard Deviation 25.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | EOT | -4.3 score on a scale | Standard Deviation 11.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 38, Day 1 | 9.1 score on a scale | Standard Deviation 5.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 28, Day 1 | 4.4 score on a scale | Standard Deviation 13.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 37, Day 1 | -5.3 score on a scale | Standard Deviation 29 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 29, Day 1 | -2.8 score on a scale | Standard Deviation 23.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 56, Day 1 | 1.8 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 36, Day 1 | 7.5 score on a scale | Standard Deviation 6.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 30, Day 1 | 9.0 score on a scale | Standard Deviation 7.5 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 31, Day 1 | -4.8 score on a scale | Standard Deviation 27.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 12, Day 1 | -3.9 score on a scale | Standard Deviation 8.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 35, Day 1 | -2.5 score on a scale | Standard Deviation 23.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 32, Day 1 | 10.3 score on a scale | Standard Deviation 6.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 33, Day 1 | 0.5 score on a scale | Standard Deviation 20.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 63, Day 1 | -18.0 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 34, Day 1 | 13.5 score on a scale | Standard Deviation 3.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 55, Day 1 | -16.8 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 13, Day 1 | -5.8 score on a scale | Standard Deviation 14.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 62, Day 1 | 4.4 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 53, Day 1 | -19.2 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 14, Day 1 | -1.6 score on a scale | Standard Deviation 17.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 7, Day 1 | -4.9 score on a scale | Standard Deviation 8.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 52, Day 1 | 6.0 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 15, Day 1 | -4.8 score on a scale | Standard Deviation 15.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 51, Day 1 | -12.0 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 16, Day 1 | -4.6 score on a scale | Standard Deviation 16.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 3, Day 1 | -3.0 score on a scale | Standard Deviation 8.5 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 50, Day 1 | 4.5 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 17, Day 1 | -4.1 score on a scale | Standard Deviation 17.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 61, Day 1 | -19.3 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 48, Day 1 | 2.4 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 18, Day 1 | -2.3 score on a scale | Standard Deviation 17.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 67, Day 1 | -21.9 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 47, Day 1 | -6.8 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 19, Day 1 | -7.7 score on a scale | Standard Deviation 19.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 60, Day 1 | 4.2 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 54, Day 1 | 4.9 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 20, Day 1 | -4.6 score on a scale | Standard Deviation 22 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 9, Day 1 | -3.7 score on a scale | Standard Deviation 10.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 46, Day 1 | 4.6 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 21, Day 1 | -3.1 score on a scale | Standard Deviation 19.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 59, Day 1 | -12.7 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 44, Day 1 | 4.3 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 22, Day 1 | -4.1 score on a scale | Standard Deviation 18.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 58, Day 1 | 5.4 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 43, Day 1 | -20.4 score on a scale | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 23, Day 1 | -4.1 score on a scale | Standard Deviation 19.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 5, Day 1 | -3.7 score on a scale | Standard Deviation 11 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 9, Day 1 | -4.2 score on a scale | Standard Deviation 5.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 3, Day 1 | 0.5 score on a scale | Standard Deviation 7.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 15, Day 1 | -6.8 score on a scale | Standard Deviation 7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 5, Day 1 | -3.7 score on a scale | Standard Deviation 7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 7, Day 1 | -2.2 score on a scale | Standard Deviation 8.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 8, Day 1 | -7.1 score on a scale | Standard Deviation 10.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 10, Day 1 | -2.7 score on a scale | Standard Deviation 6.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 11, Day 1 | -5.5 score on a scale | Standard Deviation 6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 12, Day 1 | -7.6 score on a scale | Standard Deviation 7.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 13, Day 1 | -5.9 score on a scale | Standard Deviation 8.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 14, Day 1 | -5.0 score on a scale | Standard Deviation 7.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 16, Day 1 | -6.9 score on a scale | Standard Deviation 7.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 17, Day 1 | -10.1 score on a scale | Standard Deviation 5.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 18, Day 1 | -11.5 score on a scale | Standard Deviation 8.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 19, Day 1 | -9.9 score on a scale | Standard Deviation 7.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 20, Day 1 | -9.0 score on a scale | Standard Deviation 10.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 21, Day 1 | -7.5 score on a scale | Standard Deviation 10.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 22, Day 1 | -14.5 score on a scale | Standard Deviation 9.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 23, Day 1 | -11.6 score on a scale | Standard Deviation 9.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 24, Day 1 | -18.7 score on a scale | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 25, Day 1 | -12.4 score on a scale | Standard Deviation 8.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 27, Day 1 | -13.2 score on a scale | Standard Deviation 6.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 29, Day 1 | -11.0 score on a scale | Standard Deviation 7.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 31, Day 1 | -15.6 score on a scale | Standard Deviation 4.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 33, Day 1 | -13.5 score on a scale | Standard Deviation 9 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 35, Day 1 | -11.0 score on a scale | Standard Deviation 12.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 37, Day 1 | -13.6 score on a scale | Standard Deviation 8.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 39, Day 1 | -14.3 score on a scale | Standard Deviation 8.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 41, Day 1 | -19.3 score on a scale | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 43, Day 1 | -19.9 score on a scale | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 47, Day 1 | -16.8 score on a scale | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 49, Day 1 | -15.4 score on a scale | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | EOT | -2.4 score on a scale | Standard Deviation 10.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 26, Day 1 | 0.2 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 6, Day 1 | -0.8 score on a scale | Standard Deviation 9.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 39, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 25, Day 1 | -8.4 score on a scale | Standard Deviation 3.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 24, Day 1 | -5.6 score on a scale | Standard Deviation 5.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 5, Day 1 | -0.5 score on a scale | Standard Deviation 10.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 41, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 23, Day 1 | -6.2 score on a scale | Standard Deviation 7.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 22, Day 1 | -3.6 score on a scale | Standard Deviation 5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 4, Day 1 | -2.7 score on a scale | Standard Deviation 8.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 43, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 21, Day 1 | -4.0 score on a scale | Standard Deviation 7.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 45, Day 1 | -12.3 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 20, Day 1 | -2.8 score on a scale | Standard Deviation 5.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 19, Day 1 | -6.6 score on a scale | Standard Deviation 9.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 18, Day 1 | -2.3 score on a scale | Standard Deviation 7.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 3, Day 1 | -4.3 score on a scale | Standard Deviation 8.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 47, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 17, Day 1 | 0.0 score on a scale | Standard Deviation 12.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | EOT | 2.5 score on a scale | Standard Deviation 11.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 49, Day 1 | -14.3 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 16, Day 1 | 1.9 score on a scale | Standard Deviation 7.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 15, Day 1 | -3.2 score on a scale | Standard Deviation 8.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 51, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 14, Day 1 | -1.5 score on a scale | Standard Deviation 7.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 13, Day 1 | -0.6 score on a scale | Standard Deviation 7.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 12, Day 1 | -2.8 score on a scale | Standard Deviation 6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 11, Day 1 | -4.5 score on a scale | Standard Deviation 6.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 10, Day 1 | -3.7 score on a scale | Standard Deviation 9.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 9, Day 1 | -3.6 score on a scale | Standard Deviation 10.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 2, Day 1 | -5.2 score on a scale | Standard Deviation 6.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 33, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 31, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 8, Day 1 | -2.9 score on a scale | Standard Deviation 10.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 35, Day 1 | -12.9 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 29, Day 1 | -3.7 score on a scale | Standard Deviation 13 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 28, Day 1 | 2.6 score on a scale | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 7, Day 1 | -2.0 score on a scale | Standard Deviation 12.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points | Cycle 27, Day 1 | -6.0 score on a scale | Standard Deviation 9.6 |
Secondary
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points
FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug.
Time frame: Baseline, Day 1 of Cycles 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27, 29,30,31,32,33,34,35,36,37,38, 39,40,41,43, 47,48,49,51,52,53, 54, 55,56, 57,58,60,61,62,63,67, EOT (i.e., anytime up to 64.2 months)
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. Here, '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 14, Day 1 | 2.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 3, Day 1 | 1.1 percent predicted FEV1 | Standard Deviation 4.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 5, Day 1 | -3.3 percent predicted FEV1 | Standard Deviation 8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 7, Day 1 | -3.5 percent predicted FEV1 | Standard Deviation 4.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 9, Day 1 | -1.7 percent predicted FEV1 | Standard Deviation 6.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 11, Day 1 | -4.3 percent predicted FEV1 | Standard Deviation 5.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 12, Day 1 | -2.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 13, Day 1 | -5.9 percent predicted FEV1 | Standard Deviation 9.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 15, Day 1 | -6.7 percent predicted FEV1 | Standard Deviation 11.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 16, Day 1 | 2.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 17, Day 1 | -5.3 percent predicted FEV1 | Standard Deviation 9.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 19, Day 1 | -5.2 percent predicted FEV1 | Standard Deviation 9.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 21, Day 1 | -7.4 percent predicted FEV1 | Standard Deviation 10.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 23, Day 1 | -4.3 percent predicted FEV1 | Standard Deviation 14.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 24, Day 1 | 2.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 25, Day 1 | -11.0 percent predicted FEV1 | Standard Deviation 15.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 26, Day 1 | 0.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 27, Day 1 | -6.5 percent predicted FEV1 | Standard Deviation 13.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 29, Day 1 | -0.5 percent predicted FEV1 | Standard Deviation 9.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 30, Day 1 | 3.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 31, Day 1 | -3.5 percent predicted FEV1 | Standard Deviation 12 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 32, Day 1 | 1.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 33, Day 1 | 5.0 percent predicted FEV1 | Standard Deviation 5.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 34, Day 1 | 2.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 35, Day 1 | 5.0 percent predicted FEV1 | Standard Deviation 0 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 36, Day 1 | 3.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 37, Day 1 | -1.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 38, Day 1 | 1.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 39, Day 1 | 10.0 percent predicted FEV1 | Standard Deviation 2.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 40, Day 1 | -1.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 41, Day 1 | 15.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 43, Day 1 | 16.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 47, Day 1 | 5.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 48, Day 1 | 3.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 49, Day 1 | 8.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 51, Day 1 | 8.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 52, Day 1 | 0.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 53, Day 1 | 9.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 54, Day 1 | 4.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 55, Day 1 | 13.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 56, Day 1 | 4.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 57, Day 1 | 13.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 58, Day 1 | 5.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 60, Day 1 | 4.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 61, Day 1 | 10.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 62, Day 1 | 2.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 63, Day 1 | 13.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 67, Day 1 | 14.0 percent predicted FEV1 | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | EOT | -1.4 percent predicted FEV1 | Standard Deviation 9 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 43, Day 1 | -21.0 percent predicted FEV1 | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 11, Day 1 | -4.0 percent predicted FEV1 | Standard Deviation 8.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 22, Day 1 | -11.0 percent predicted FEV1 | Standard Deviation 1.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 31, Day 1 | -19.5 percent predicted FEV1 | Standard Deviation 10.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 12, Day 1 | -1.0 percent predicted FEV1 | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 29, Day 1 | 17.0 percent predicted FEV1 | Standard Deviation 11.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 5, Day 1 | -5.0 percent predicted FEV1 | Standard Deviation 6.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 13, Day 1 | -2.5 percent predicted FEV1 | Standard Deviation 14.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 35, Day 1 | -2.5 percent predicted FEV1 | Standard Deviation 30.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 24, Day 1 | -18.0 percent predicted FEV1 | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 14, Day 1 | 0.0 percent predicted FEV1 | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 27, Day 1 | -17.0 percent predicted FEV1 | Standard Deviation 9.9 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 7, Day 1 | -2.6 percent predicted FEV1 | Standard Deviation 9.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 15, Day 1 | -2.3 percent predicted FEV1 | Standard Deviation 5.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | EOT | -10.1 percent predicted FEV1 | Standard Deviation 15.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 39, Day 1 | -23.0 percent predicted FEV1 | Standard Deviation 11.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 16, Day 1 | -8.0 percent predicted FEV1 | Standard Deviation 15.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 8, Day 1 | 1.0 percent predicted FEV1 | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 33, Day 1 | -1.0 percent predicted FEV1 | Standard Deviation 33.9 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 17, Day 1 | -6.0 percent predicted FEV1 | Standard Deviation 7.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 23, Day 1 | -12.5 percent predicted FEV1 | Standard Deviation 4.9 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 18, Day 1 | -7.5 percent predicted FEV1 | Standard Deviation 10.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 37, Day 1 | -22.0 percent predicted FEV1 | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 9, Day 1 | -5.9 percent predicted FEV1 | Standard Deviation 11.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 19, Day 1 | -6.3 percent predicted FEV1 | Standard Deviation 5.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 3, Day 1 | -1.8 percent predicted FEV1 | Standard Deviation 7.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 20, Day 1 | -8.0 percent predicted FEV1 | Standard Deviation 7.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 10, Day 1 | -6.0 percent predicted FEV1 | Standard Deviation 8.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 25, Day 1 | -12.5 percent predicted FEV1 | Standard Deviation 3.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 21, Day 1 | 0.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 39, Day 1 | -5.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 19, Day 1 | 0.5 percent predicted FEV1 | Standard Deviation 8.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 20, Day 1 | 4.0 percent predicted FEV1 | Standard Deviation 10.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | EOT | -7.4 percent predicted FEV1 | Standard Deviation 14.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 31, Day 1 | -4.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 22, Day 1 | -6.0 percent predicted FEV1 | Standard Deviation 17 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 23, Day 1 | -4.8 percent predicted FEV1 | Standard Deviation 11.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 24, Day 1 | -19.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 35, Day 1 | -4.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 25, Day 1 | -5.0 percent predicted FEV1 | Standard Deviation 11.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 47, Day 1 | -5.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 36, Day 1 | 5.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 27, Day 1 | -10.0 percent predicted FEV1 | Standard Deviation 17 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 49, Day 1 | -2.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 3, Day 1 | -1.5 percent predicted FEV1 | Standard Deviation 6.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 4, Day 1 | -0.2 percent predicted FEV1 | Standard Deviation 8.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 5, Day 1 | 0.5 percent predicted FEV1 | Standard Deviation 5.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 6, Day 1 | -0.9 percent predicted FEV1 | Standard Deviation 6.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 29, Day 1 | 0.0 percent predicted FEV1 | Standard Deviation 1.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 7, Day 1 | -0.9 percent predicted FEV1 | Standard Deviation 11.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 8, Day 1 | -1.1 percent predicted FEV1 | Standard Deviation 8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 9, Day 1 | -3.0 percent predicted FEV1 | Standard Deviation 11.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 10, Day 1 | 2.7 percent predicted FEV1 | Standard Deviation 3.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 11, Day 1 | -4.4 percent predicted FEV1 | Standard Deviation 15.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 12, Day 1 | 0.3 percent predicted FEV1 | Standard Deviation 3.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 21, Day 1 | -10.0 percent predicted FEV1 | Standard Deviation 19.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 13, Day 1 | -3.5 percent predicted FEV1 | Standard Deviation 13.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 2, Day 1 | -4.8 percent predicted FEV1 | Standard Deviation 6.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 14, Day 1 | -5.1 percent predicted FEV1 | Standard Deviation 9.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 43, Day 1 | -7.0 percent predicted FEV1 | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 15, Day 1 | -6.1 percent predicted FEV1 | Standard Deviation 12.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 16, Day 1 | -4.5 percent predicted FEV1 | Standard Deviation 7.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 17, Day 1 | -7.9 percent predicted FEV1 | Standard Deviation 15.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Each Specified Time Points | Cycle 18, Day 1 | 4.0 percent predicted FEV1 | Standard Deviation 6 |
Secondary
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points
FVC was the total amount of air (in liters) exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug.
Time frame: Baseline, Day 1 of Cycles 2, 3,4, 5,6,7,8,9,10,11,12,13, 14,15,16,17,18,19,20,21,22,23,24,25,26, 27,29,30,31,32,33,34,35,36,37,38,39,40,41,43,47, 48,49, 51,52,53,54, 55, 56,57,58,60,61, 62, 63,67, EOT (i.e., anytime up to 64.2 months)
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. Here, '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 38, Day 1 | 2.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 3, Day 1 | 0.5 percent predicted FVC | Standard Deviation 3.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 5, Day 1 | -0.5 percent predicted FVC | Standard Deviation 7.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 7, Day 1 | -2.9 percent predicted FVC | Standard Deviation 5.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 9, Day 1 | 0.4 percent predicted FVC | Standard Deviation 5.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 11, Day 1 | -1.1 percent predicted FVC | Standard Deviation 7.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 12, Day 1 | 2.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 13, Day 1 | -2.4 percent predicted FVC | Standard Deviation 7.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 14, Day 1 | 11.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 15, Day 1 | -3.7 percent predicted FVC | Standard Deviation 10.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 16, Day 1 | 16.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 17, Day 1 | -3.2 percent predicted FVC | Standard Deviation 6.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 19, Day 1 | -2.3 percent predicted FVC | Standard Deviation 6.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 21, Day 1 | -3.2 percent predicted FVC | Standard Deviation 8.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 23, Day 1 | 0.0 percent predicted FVC | Standard Deviation 12.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 24, Day 1 | 4.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 25, Day 1 | -7.0 percent predicted FVC | Standard Deviation 11.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 26, Day 1 | 4.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 27, Day 1 | -2.0 percent predicted FVC | Standard Deviation 4.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 29, Day 1 | 2.5 percent predicted FVC | Standard Deviation 4.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 30, Day 1 | 4.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 31, Day 1 | 1.5 percent predicted FVC | Standard Deviation 3.5 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 32, Day 1 | 2.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 33, Day 1 | 11.0 percent predicted FVC | Standard Deviation 0 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 34, Day 1 | 6.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 35, Day 1 | 11.0 percent predicted FVC | Standard Deviation 5.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 36, Day 1 | 5.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 37, Day 1 | 7.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 60, Day 1 | 8.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 39, Day 1 | 12.5 percent predicted FVC | Standard Deviation 0.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 40, Day 1 | 3.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 41, Day 1 | 15.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 43, Day 1 | 17.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 47, Day 1 | 5.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 48, Day 1 | 5.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 49, Day 1 | 6.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 51, Day 1 | 9.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 52, Day 1 | 3.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 53, Day 1 | 8.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 54, Day 1 | 5.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 55, Day 1 | 13.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 56, Day 1 | 7.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 57, Day 1 | 14.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 58, Day 1 | 7.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 61, Day 1 | 12.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 62, Day 1 | 5.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 63, Day 1 | 12.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 67, Day 1 | 14.0 percent predicted FVC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | EOT | -2.5 percent predicted FVC | Standard Deviation 10.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 3, Day 1 | -2.4 percent predicted FVC | Standard Deviation 6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | EOT | -8.4 percent predicted FVC | Standard Deviation 9.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 11, Day 1 | -2.7 percent predicted FVC | Standard Deviation 5.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 25, Day 1 | -10.5 percent predicted FVC | Standard Deviation 3.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 37, Day 1 | -24.0 percent predicted FVC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 12, Day 1 | 1.0 percent predicted FVC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 5, Day 1 | -4.3 percent predicted FVC | Standard Deviation 5.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 31, Day 1 | -15.5 percent predicted FVC | Standard Deviation 7.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 13, Day 1 | -3.3 percent predicted FVC | Standard Deviation 15.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 22, Day 1 | -11.0 percent predicted FVC | Standard Deviation 0 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 35, Day 1 | -15.0 percent predicted FVC | Standard Deviation 11.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 14, Day 1 | 2.0 percent predicted FVC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 29, Day 1 | -11.0 percent predicted FVC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 39, Day 1 | -20.5 percent predicted FVC | Standard Deviation 12 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 15, Day 1 | -3.3 percent predicted FVC | Standard Deviation 5.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 7, Day 1 | -1.3 percent predicted FVC | Standard Deviation 6.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 43, Day 1 | -18.0 percent predicted FVC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 16, Day 1 | -6.0 percent predicted FVC | Standard Deviation 19.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 8, Day 1 | 2.0 percent predicted FVC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 33, Day 1 | -17.5 percent predicted FVC | Standard Deviation 7.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 17, Day 1 | -3.0 percent predicted FVC | Standard Deviation 11.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 27, Day 1 | -18.0 percent predicted FVC | Standard Deviation 12.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 18, Day 1 | -7.5 percent predicted FVC | Standard Deviation 9.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 24, Day 1 | -13.0 percent predicted FVC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 9, Day 1 | -2.9 percent predicted FVC | Standard Deviation 5.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 19, Day 1 | -5.3 percent predicted FVC | Standard Deviation 4.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 23, Day 1 | -11.0 percent predicted FVC | Standard Deviation 2.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 20, Day 1 | -10.5 percent predicted FVC | Standard Deviation 2.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 10, Day 1 | -5.0 percent predicted FVC | Standard Deviation 8.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 21, Day 1 | -3.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 18, Day 1 | 4.0 percent predicted FVC | Standard Deviation 4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 47, Day 1 | -2.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 19, Day 1 | 0.8 percent predicted FVC | Standard Deviation 5.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 20, Day 1 | -2.0 percent predicted FVC | Standard Deviation 5.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | EOT | -7.8 percent predicted FVC | Standard Deviation 14.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 21, Day 1 | -6.6 percent predicted FVC | Standard Deviation 17 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 22, Day 1 | -6.0 percent predicted FVC | Standard Deviation 8.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 23, Day 1 | -1.8 percent predicted FVC | Standard Deviation 10.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 35, Day 1 | -3.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 24, Day 1 | -15.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 25, Day 1 | -1.3 percent predicted FVC | Standard Deviation 11.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 36, Day 1 | 2.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 2, Day 1 | -5.5 percent predicted FVC | Standard Deviation 9.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 27, Day 1 | -4.0 percent predicted FVC | Standard Deviation 21.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 3, Day 1 | -3.0 percent predicted FVC | Standard Deviation 6.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 4, Day 1 | -0.2 percent predicted FVC | Standard Deviation 8.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 5, Day 1 | 1.6 percent predicted FVC | Standard Deviation 6.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 6, Day 1 | 0.8 percent predicted FVC | Standard Deviation 9.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 7, Day 1 | 2.3 percent predicted FVC | Standard Deviation 9.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 8, Day 1 | 0.4 percent predicted FVC | Standard Deviation 8.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 29, Day 1 | 6.0 percent predicted FVC | Standard Deviation 1.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 9, Day 1 | -0.8 percent predicted FVC | Standard Deviation 9.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 10, Day 1 | 4.7 percent predicted FVC | Standard Deviation 4.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 43, Day 1 | -4.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 11, Day 1 | -4.4 percent predicted FVC | Standard Deviation 12 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 49, Day 1 | 2.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 12, Day 1 | 0.7 percent predicted FVC | Standard Deviation 5.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 13, Day 1 | -4.9 percent predicted FVC | Standard Deviation 9.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 31, Day 1 | -4.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 14, Day 1 | -2.7 percent predicted FVC | Standard Deviation 7.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 15, Day 1 | -4.8 percent predicted FVC | Standard Deviation 11.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 39, Day 1 | -1.0 percent predicted FVC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 16, Day 1 | -6.5 percent predicted FVC | Standard Deviation 6.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Each Specified Time Points | Cycle 17, Day 1 | -5.6 percent predicted FVC | Standard Deviation 12.8 |
Secondary
Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points
DLco is a measurement of the ability of the lungs to transfer gases from the air to the blood. Change from baseline in diffusing capacity of the lung for carbon monoxide (percent predicted hemoglobin level corrected) was reported for this measure. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug.
Time frame: Baseline, Day 1 of Cycles 2,3,4,5,6,7,8,9,10,11,12,13, 14,15,16,17,18,19,20,21,22,23,24,25,26,27, 29,31,32,33,34,35,36,37,39,40,41,43,47,49,51,53,55, 61, 62, 63, 67, EOT (i.e., anytime up to 64.2 Months)
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. Here, '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 35, Day 1 | 13.867 Percent Predicted HGB Corrected DLco | Standard Deviation 1.309 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 3, Day 1 | 4.545 Percent Predicted HGB Corrected DLco | Standard Deviation 22.991 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 19, Day 1 | -2.293 Percent Predicted HGB Corrected DLco | Standard Deviation 5.763 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 40, Day 1 | 5.586 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 41, Day 1 | 22.884 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 43, Day 1 | 15.213 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 33, Day 1 | 9.901 Percent Predicted HGB Corrected DLco | Standard Deviation 9.954 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 21, Day 1 | -2.778 Percent Predicted HGB Corrected DLco | Standard Deviation 8.187 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 5, Day 1 | 4.635 Percent Predicted HGB Corrected DLco | Standard Deviation 23.989 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 11, Day 1 | -0.625 Percent Predicted HGB Corrected DLco | Standard Deviation 7.262 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 47, Day 1 | 9.660 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 49, Day 1 | -3.599 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 23, Day 1 | 0.354 Percent Predicted HGB Corrected DLco | Standard Deviation 1.844 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 51, Day 1 | 11.734 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 7, Day 1 | 1.521 Percent Predicted HGB Corrected DLco | Standard Deviation 19.836 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 24, Day 1 | 6.945 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 53, Day 1 | 10.292 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 12, Day 1 | 0.531 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 25, Day 1 | -4.461 Percent Predicted HGB Corrected DLco | Standard Deviation 19.865 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 55, Day 1 | 16.550 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 61, Day 1 | 17.682 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 26, Day 1 | 4.715 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 27, Day 1 | -8.047 Percent Predicted HGB Corrected DLco | Standard Deviation 24.788 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 62, Day 1 | 4.170 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 63, Day 1 | 26.215 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 29, Day 1 | -6.701 Percent Predicted HGB Corrected DLco | Standard Deviation 1.671 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 67, Day 1 | 41.384 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 13, Day 1 | -5.548 Percent Predicted HGB Corrected DLco | Standard Deviation 12.175 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 31, Day 1 | 2.343 Percent Predicted HGB Corrected DLco | Standard Deviation 20.988 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | EOT | -1.962 Percent Predicted HGB Corrected DLco | Standard Deviation 11.426 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 36, Day 1 | 4.166 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 15, Day 1 | 0.228 Percent Predicted HGB Corrected DLco | Standard Deviation 15.731 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 14, Day 1 | 12.916 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 37, Day 1 | 9.306 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 16, Day 1 | 48.465 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 32, Day 1 | 5.586 Percent Predicted HGB Corrected DLco | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 9, Day 1 | -4.514 Percent Predicted HGB Corrected DLco | Standard Deviation 7.401 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 17, Day 1 | -1.018 Percent Predicted HGB Corrected DLco | Standard Deviation 9.226 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 39, Day 1 | 14.754 Percent Predicted HGB Corrected DLco | Standard Deviation 0.649 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 34, Day 1 | 4.863 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 31, Day 1 | -0.800 Percent Predicted HGB Corrected DLco | Standard Deviation 17.528 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 33, Day 1 | -5.962 Percent Predicted HGB Corrected DLco | Standard Deviation 10.55 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 35, Day 1 | -0.426 Percent Predicted HGB Corrected DLco | Standard Deviation 6.677 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 37, Day 1 | -19.228 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 39, Day 1 | -6.813 Percent Predicted HGB Corrected DLco | Standard Deviation 12.81 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 14, Day 1 | 0.358 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 43, Day 1 | 8.775 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 8, Day 1 | 3.554 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | EOT | 0.985 Percent Predicted HGB Corrected DLco | Standard Deviation 5.919 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 15, Day 1 | 1.125 Percent Predicted HGB Corrected DLco | Standard Deviation 5.927 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 5, Day 1 | -4.462 Percent Predicted HGB Corrected DLco | Standard Deviation 23.621 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 16, Day 1 | -6.618 Percent Predicted HGB Corrected DLco | Standard Deviation 15.443 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 17, Day 1 | 8.458 Percent Predicted HGB Corrected DLco | Standard Deviation 6.229 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 9, Day 1 | 2.570 Percent Predicted HGB Corrected DLco | Standard Deviation 8.902 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 18, Day 1 | 15.543 Percent Predicted HGB Corrected DLco | Standard Deviation 11.753 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 19, Day 1 | 1.824 Percent Predicted HGB Corrected DLco | Standard Deviation 8.539 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 10, Day 1 | 4.343 Percent Predicted HGB Corrected DLco | Standard Deviation 3.144 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 20, Day 1 | -14.692 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 3, Day 1 | -0.638 Percent Predicted HGB Corrected DLco | Standard Deviation 7.059 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 21, Day 1 | -10.661 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 22, Day 1 | 3.347 Percent Predicted HGB Corrected DLco | Standard Deviation 3.56 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 11, Day 1 | 6.582 Percent Predicted HGB Corrected DLco | Standard Deviation 10.695 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 23, Day 1 | -15.184 Percent Predicted HGB Corrected DLco | Standard Deviation 20.181 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 24, Day 1 | -18.095 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 25, Day 1 | 6.289 Percent Predicted HGB Corrected DLco | Standard Deviation 2.469 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 12, Day 1 | 4.076 Percent Predicted HGB Corrected DLco | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 27, Day 1 | -9.914 Percent Predicted HGB Corrected DLco | Standard Deviation 15.387 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 7, Day 1 | 6.184 Percent Predicted HGB Corrected DLco | Standard Deviation 9.436 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 29, Day 1 | -18.814 Percent Predicted HGB Corrected DLco | Standard Deviation 24.96 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 13, Day 1 | 1.882 Percent Predicted HGB Corrected DLco | Standard Deviation 7.522 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | EOT | -10.371 Percent Predicted HGB Corrected DLco | Standard Deviation 14.208 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 3, Day 1 | -3.928 Percent Predicted HGB Corrected DLco | Standard Deviation 9.492 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 4, Day 1 | 0.278 Percent Predicted HGB Corrected DLco | Standard Deviation 9.683 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 5, Day 1 | -4.111 Percent Predicted HGB Corrected DLco | Standard Deviation 9.138 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 6, Day 1 | -3.143 Percent Predicted HGB Corrected DLco | Standard Deviation 10.385 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 7, Day 1 | -4.275 Percent Predicted HGB Corrected DLco | Standard Deviation 11.464 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 8, Day 1 | -3.787 Percent Predicted HGB Corrected DLco | Standard Deviation 11.983 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 9, Day 1 | -2.540 Percent Predicted HGB Corrected DLco | Standard Deviation 11.897 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 10, Day 1 | 1.328 Percent Predicted HGB Corrected DLco | Standard Deviation 8.887 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 11, Day 1 | -2.720 Percent Predicted HGB Corrected DLco | Standard Deviation 10.92 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 12, Day 1 | -1.378 Percent Predicted HGB Corrected DLco | Standard Deviation 6.364 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 13, Day 1 | 2.091 Percent Predicted HGB Corrected DLco | Standard Deviation 13.29 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 14, Day 1 | 0.309 Percent Predicted HGB Corrected DLco | Standard Deviation 11.651 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 15, Day 1 | -5.309 Percent Predicted HGB Corrected DLco | Standard Deviation 11.514 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 16, Day 1 | -6.840 Percent Predicted HGB Corrected DLco | Standard Deviation 15.053 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 17, Day 1 | -10.865 Percent Predicted HGB Corrected DLco | Standard Deviation 13.346 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 18, Day 1 | -3.174 Percent Predicted HGB Corrected DLco | Standard Deviation 3.106 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 19, Day 1 | -2.020 Percent Predicted HGB Corrected DLco | Standard Deviation 2.436 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 20, Day 1 | -13.517 Percent Predicted HGB Corrected DLco | Standard Deviation 5.936 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 21, Day 1 | -12.354 Percent Predicted HGB Corrected DLco | Standard Deviation 12.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 22, Day 1 | -17.222 Percent Predicted HGB Corrected DLco | Standard Deviation 16.947 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 23, Day 1 | -2.219 Percent Predicted HGB Corrected DLco | Standard Deviation 10.614 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 24, Day 1 | -11.430 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 25, Day 1 | -13.392 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 27, Day 1 | -11.154 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 29, Day 1 | 8.613 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 31, Day 1 | 10.833 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 35, Day 1 | 5.088 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 36, Day 1 | 10.372 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 39, Day 1 | 5.902 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 43, Day 1 | 16.351 Percent Predicted HGB Corrected DLco | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Hemoglobin (HGB) Corrected Diffusing Capacity of Lung for Carbon Monoxide (DLco) at Each Specified Time Points | Cycle 2, Day 1 | -5.243 Percent Predicted HGB Corrected DLco | Standard Deviation 9.83 |
Secondary
Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points
RV is the volume of air remaining in the lungs after maximum forceful expiration. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug.
Time frame: Baseline, Day 1 of Cycles 2, 3, 4,5, 6,7, 8, 9, 10, 11,12, 13, 14,15, 16,17, 18, 19,20, 21,22,23, 24, 25, 26,27, 29, 30, 31, 32, 33,34, 35,36, 37,38, 39, 40,41, 43,47, 48, 49,51,52,53, 54, 55,56,57, 58,60,61,62,63,67, EOT (i.e., anytime up to 64.2 Months)
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. Here, '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 21, Day 1 | 8.3 percent predicted RV | Standard Deviation 10 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 67, Day 1 | 2.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 40, Day 1 | -1.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 57, Day 1 | 18.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 39, Day 1 | 43.0 percent predicted RV | Standard Deviation 89.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 23, Day 1 | 0.3 percent predicted RV | Standard Deviation 5.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 63, Day 1 | 6.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 38, Day 1 | 8.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 24, Day 1 | -4.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 56, Day 1 | 17.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 37, Day 1 | -54.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 25, Day 1 | 1.0 percent predicted RV | Standard Deviation 9.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 11, Day 1 | 22.1 percent predicted RV | Standard Deviation 29.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 36, Day 1 | 17.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 26, Day 1 | -3.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 27, Day 1 | 19.5 percent predicted RV | Standard Deviation 41.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 5, Day 1 | 5.2 percent predicted RV | Standard Deviation 24.5 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 35, Day 1 | 3.5 percent predicted RV | Standard Deviation 36.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 29, Day 1 | -13.0 percent predicted RV | Standard Deviation 42.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 55, Day 1 | 53.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 33, Day 1 | 14.5 percent predicted RV | Standard Deviation 36.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 30, Day 1 | 21.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 31, Day 1 | 15.0 percent predicted RV | Standard Deviation 43.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 12, Day 1 | -28.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 32, Day 1 | 5.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | EOT | 6.3 percent predicted RV | Standard Deviation 24.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 54, Day 1 | 4.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 13, Day 1 | 20.3 percent predicted RV | Standard Deviation 19.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 62, Day 1 | -8.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 53, Day 1 | 22.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 14, Day 1 | 78.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 61, Day 1 | -18.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 52, Day 1 | -4.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 15, Day 1 | 20.3 percent predicted RV | Standard Deviation 27.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 7, Day 1 | 4.9 percent predicted RV | Standard Deviation 29.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 51, Day 1 | 22.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 16, Day 1 | 0.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 3, Day 1 | 0.2 percent predicted RV | Standard Deviation 22.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 49, Day 1 | -14.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 17, Day 1 | 13.6 percent predicted RV | Standard Deviation 27.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 60, Day 1 | -20.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 48, Day 1 | -50.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 34, Day 1 | -1.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 47, Day 1 | 42.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 19, Day 1 | 5.4 percent predicted RV | Standard Deviation 28.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 58, Day 1 | 4.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 43, Day 1 | 58.0 percent predicted RV | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 9, Day 1 | 6.4 percent predicted RV | Standard Deviation 27.4 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 41, Day 1 | 80.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 18, Day 1 | -42.0 percent predicted RV | Standard Deviation 0 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 3, Day 1 | -4.6 percent predicted RV | Standard Deviation 18.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 5, Day 1 | -11.5 percent predicted RV | Standard Deviation 26.9 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 7, Day 1 | -9.9 percent predicted RV | Standard Deviation 17.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 8, Day 1 | -28.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 9, Day 1 | -19.9 percent predicted RV | Standard Deviation 24.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 10, Day 1 | -47.5 percent predicted RV | Standard Deviation 0.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 11, Day 1 | -10.5 percent predicted RV | Standard Deviation 28.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 12, Day 1 | -5.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 13, Day 1 | -27.0 percent predicted RV | Standard Deviation 35.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 14, Day 1 | -31.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 15, Day 1 | -0.7 percent predicted RV | Standard Deviation 18.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 16, Day 1 | -36.5 percent predicted RV | Standard Deviation 13.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 17, Day 1 | -47.3 percent predicted RV | Standard Deviation 25.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 33, Day 1 | -70.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 19, Day 1 | -19.7 percent predicted RV | Standard Deviation 18 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 20, Day 1 | -7.5 percent predicted RV | Standard Deviation 37.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 21, Day 1 | -44.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 22, Day 1 | -33.0 percent predicted RV | Standard Deviation 19.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 23, Day 1 | -72.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 24, Day 1 | -17.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 25, Day 1 | -34.0 percent predicted RV | Standard Deviation 31.1 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 27, Day 1 | -39.5 percent predicted RV | Standard Deviation 20.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 29, Day 1 | -13.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 31, Day 1 | -93.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 35, Day 1 | -34.5 percent predicted RV | Standard Deviation 33.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 37, Day 1 | -70.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 39, Day 1 | -43.0 percent predicted RV | Standard Deviation 42.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 43, Day 1 | -26.0 percent predicted RV | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | EOT | 10.6 percent predicted RV | Standard Deviation 34.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 25, Day 1 | -23.3 percent predicted RV | Standard Deviation 56 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 36, Day 1 | -20.0 percent predicted RV | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 24, Day 1 | -78.0 percent predicted RV | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 3, Day 1 | 9.0 percent predicted RV | Standard Deviation 34.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 23, Day 1 | 1.5 percent predicted RV | Standard Deviation 44.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 22, Day 1 | -41.0 percent predicted RV | Standard Deviation 46.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 2, Day 1 | -18.0 percent predicted RV | Standard Deviation 30.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 39, Day 1 | 81.0 percent predicted RV | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 21, Day 1 | -30.2 percent predicted RV | Standard Deviation 51.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 20, Day 1 | -22.0 percent predicted RV | Standard Deviation 44.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 19, Day 1 | -23.5 percent predicted RV | Standard Deviation 18.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | EOT | -18.5 percent predicted RV | Standard Deviation 32.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 43, Day 1 | 75.0 percent predicted RV | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 18, Day 1 | -7.3 percent predicted RV | Standard Deviation 33.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 47, Day 1 | 87.0 percent predicted RV | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 17, Day 1 | -39.1 percent predicted RV | Standard Deviation 26.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 16, Day 1 | -27.5 percent predicted RV | Standard Deviation 31.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 49, Day 1 | -5.0 percent predicted RV | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 15, Day 1 | -16.7 percent predicted RV | Standard Deviation 22.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 14, Day 1 | -6.5 percent predicted RV | Standard Deviation 36.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 13, Day 1 | 0.3 percent predicted RV | Standard Deviation 32.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 12, Day 1 | -22.2 percent predicted RV | Standard Deviation 49.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 11, Day 1 | 5.4 percent predicted RV | Standard Deviation 38 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 10, Day 1 | 1.4 percent predicted RV | Standard Deviation 38.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 9, Day 1 | 0.1 percent predicted RV | Standard Deviation 35.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 8, Day 1 | 2.5 percent predicted RV | Standard Deviation 39.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 7, Day 1 | -7.5 percent predicted RV | Standard Deviation 33 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 6, Day 1 | -10.9 percent predicted RV | Standard Deviation 37.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 5, Day 1 | -3.7 percent predicted RV | Standard Deviation 29.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 31, Day 1 | 61.0 percent predicted RV | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 29, Day 1 | 17.5 percent predicted RV | Standard Deviation 40.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 27, Day 1 | -41.0 percent predicted RV | Standard Deviation 28.3 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 4, Day 1 | 17.8 percent predicted RV | Standard Deviation 29 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Residual Volume (RV) at Each Specified Time Points | Cycle 35, Day 1 | 47.0 percent predicted RV | — |
Secondary
Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points
TLC is the volume of air in the lungs upon the maximum effort of inspiration. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. EOT visit was performed within 3 days after the participant's last dose of study drug.
Time frame: Baseline, Day 1 of Cycles 2,3, 4, 5,6,7, 8, 9, 10,11,12,13, 14, 15, 16, 17, 18, 19, 20,21, 22,23,24, 25, 26, 27,29, 30, 31,32, 33, 34, 35,36, 37, 38,39, 40,41,43,47, 48, 49,51,52,53, 54,55,56,57,58, 60,61,62, 63, 67, EOT (i.e., anytime up to 64.2 Months)
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. Here, '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 13, Day 1 | -0.3 Percent Predicted TLC | Standard Deviation 7.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 47, Day 1 | 19.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 25, Day 1 | -3.0 Percent Predicted TLC | Standard Deviation 7.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 9, Day 1 | -2.9 Percent Predicted TLC | Standard Deviation 6.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 43, Day 1 | 33.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 26, Day 1 | 0.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 27, Day 1 | 5.5 Percent Predicted TLC | Standard Deviation 16.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 60, Day 1 | -3.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 41, Day 1 | 38.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 29, Day 1 | -1.0 Percent Predicted TLC | Standard Deviation 17 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 14, Day 1 | 23.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 40, Day 1 | 0.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 30, Day 1 | 7.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 31, Day 1 | 7.5 Percent Predicted TLC | Standard Deviation 17.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 5, Day 1 | -2.6 Percent Predicted TLC | Standard Deviation 16.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 39, Day 1 | 24.0 Percent Predicted TLC | Standard Deviation 28.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 32, Day 1 | 1.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 33, Day 1 | 14.0 Percent Predicted TLC | Standard Deviation 11.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 58, Day 1 | 5.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 34, Day 1 | 2.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 35, Day 1 | 10.5 Percent Predicted TLC | Standard Deviation 7.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 15, Day 1 | -2.8 Percent Predicted TLC | Standard Deviation 10.8 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 38, Day 1 | 2.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 36, Day 1 | 6.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 37, Day 1 | -7.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 67, Day 1 | 12.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 57, Day 1 | 18.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 16, Day 1 | -3.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 3, Day 1 | 1.6 Percent Predicted TLC | Standard Deviation 11.9 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 56, Day 1 | 9.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 17, Day 1 | -3.0 Percent Predicted TLC | Standard Deviation 6.2 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 63, Day 1 | 12.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 55, Day 1 | 29.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 11, Day 1 | 0.7 Percent Predicted TLC | Standard Deviation 4.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 54, Day 1 | 4.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 19, Day 1 | -4.6 Percent Predicted TLC | Standard Deviation 6.1 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 7, Day 1 | -3.7 Percent Predicted TLC | Standard Deviation 6.6 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 53, Day 1 | 15.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 62, Day 1 | -1.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 52, Day 1 | 1.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 21, Day 1 | 0.3 Percent Predicted TLC | Standard Deviation 9.3 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 12, Day 1 | -9.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 51, Day 1 | 15.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | EOT | 5.2 Percent Predicted TLC | Standard Deviation 27.5 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 49, Day 1 | 5.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 23, Day 1 | 0.0 Percent Predicted TLC | Standard Deviation 8.7 |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 61, Day 1 | 5.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 48, Day 1 | -13.0 Percent Predicted TLC | — |
| Cohort 1: Belumosudil 200 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 24, Day 1 | 0.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 5, Day 1 | -7.2 Percent Predicted TLC | Standard Deviation 10.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 7, Day 1 | -4.4 Percent Predicted TLC | Standard Deviation 6.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 8, Day 1 | -5.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 9, Day 1 | -6.0 Percent Predicted TLC | Standard Deviation 8.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 10, Day 1 | -18.5 Percent Predicted TLC | Standard Deviation 6.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 11, Day 1 | -5.2 Percent Predicted TLC | Standard Deviation 11.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 12, Day 1 | 0.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 13, Day 1 | -10.3 Percent Predicted TLC | Standard Deviation 18.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 14, Day 1 | -7.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 15, Day 1 | -1.0 Percent Predicted TLC | Standard Deviation 5.6 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 16, Day 1 | -14.0 Percent Predicted TLC | Standard Deviation 12.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 17, Day 1 | -17.0 Percent Predicted TLC | Standard Deviation 11.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 18, Day 1 | -16.0 Percent Predicted TLC | Standard Deviation 8.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 19, Day 1 | -7.7 Percent Predicted TLC | Standard Deviation 10.5 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 20, Day 1 | -9.5 Percent Predicted TLC | Standard Deviation 16.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 21, Day 1 | -18.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 22, Day 1 | -18.5 Percent Predicted TLC | Standard Deviation 6.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 23, Day 1 | -21.0 Percent Predicted TLC | Standard Deviation 19.8 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 24, Day 1 | -15.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 25, Day 1 | -19.5 Percent Predicted TLC | Standard Deviation 13.4 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 27, Day 1 | -24.0 Percent Predicted TLC | Standard Deviation 12.7 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 29, Day 1 | -27.5 Percent Predicted TLC | Standard Deviation 21.9 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 31, Day 1 | -36.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 33, Day 1 | -39.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 35, Day 1 | -23.5 Percent Predicted TLC | Standard Deviation 16.3 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 37, Day 1 | -41.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 39, Day 1 | -30.0 Percent Predicted TLC | Standard Deviation 21.2 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 43, Day 1 | -16.0 Percent Predicted TLC | — |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | EOT | -2.4 Percent Predicted TLC | Standard Deviation 15 |
| Cohort 2: Belumosudil 200 mg BID | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 3, Day 1 | 1.9 Percent Predicted TLC | Standard Deviation 8.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 39, Day 1 | 23.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 29, Day 1 | 12.0 Percent Predicted TLC | Standard Deviation 14.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 27, Day 1 | -14.5 Percent Predicted TLC | Standard Deviation 24.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 25, Day 1 | -6.3 Percent Predicted TLC | Standard Deviation 24.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 4, Day 1 | 3.3 Percent Predicted TLC | Standard Deviation 14 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 43, Day 1 | 21.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 24, Day 1 | -34.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 47, Day 1 | 25.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 23, Day 1 | -2.8 Percent Predicted TLC | Standard Deviation 18.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 22, Day 1 | -21.0 Percent Predicted TLC | Standard Deviation 14.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 49, Day 1 | 1.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 21, Day 1 | -14.4 Percent Predicted TLC | Standard Deviation 24 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 20, Day 1 | -9.3 Percent Predicted TLC | Standard Deviation 15.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 19, Day 1 | -7.0 Percent Predicted TLC | Standard Deviation 5.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 18, Day 1 | 0.0 Percent Predicted TLC | Standard Deviation 13.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 17, Day 1 | -18.1 Percent Predicted TLC | Standard Deviation 15.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 16, Day 1 | -15.5 Percent Predicted TLC | Standard Deviation 9.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 15, Day 1 | -7.0 Percent Predicted TLC | Standard Deviation 12 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 14, Day 1 | -5.8 Percent Predicted TLC | Standard Deviation 16.5 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 13, Day 1 | -3.3 Percent Predicted TLC | Standard Deviation 17.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 12, Day 1 | -8.0 Percent Predicted TLC | Standard Deviation 14.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 11, Day 1 | -3.0 Percent Predicted TLC | Standard Deviation 19.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 10, Day 1 | 3.6 Percent Predicted TLC | Standard Deviation 14.7 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 9, Day 1 | -0.9 Percent Predicted TLC | Standard Deviation 15.8 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 8, Day 1 | -0.2 Percent Predicted TLC | Standard Deviation 12.9 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 6, Day 1 | -4.4 Percent Predicted TLC | Standard Deviation 11.6 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | EOT | -12.6 Percent Predicted TLC | Standard Deviation 20.1 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 2, Day 1 | -9.0 Percent Predicted TLC | Standard Deviation 13.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 7, Day 1 | -2.6 Percent Predicted TLC | Standard Deviation 13.4 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 36, Day 1 | -6.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 5, Day 1 | -1.7 Percent Predicted TLC | Standard Deviation 11.2 |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 35, Day 1 | 13.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 31, Day 1 | 17.0 Percent Predicted TLC | — |
| Cohort 3: Belumosudil 400 mg QD | Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Each Specified Time Points | Cycle 3, Day 1 | -0.6 Percent Predicted TLC | Standard Deviation 14.8 |
Secondary
Duration of Response (DOR)
The DOR was defined as the time (in weeks) from first documentation of response to the time of first documentation of deterioration from best response (e.g., CR to PR, or PR to LR). LOR included the response status of unchanged (LOR-U), mixed (LOR-M), or progression (LOR-P). Per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria; CR was defined as the resolution of all manifestations in each organ or site; PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; LOR-M was defined as CR or PR in at least one organ accompanied by progression in another organ, LOR-U was defined as outcomes that did not meet the criteria for CR, PR, progression or mixed response, LOR-P was defined as progression in at least one organ or site without a response in any other organ or site. Kaplan-Meier was used for the analysis.
Time frame: From the date of first response until documented disease progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on responder population which included participants who received at least 1 dose of study medication and achieved a PR or CR response at any post-baseline response assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Duration of Response (DOR) | 40.0 weeks |
| Cohort 2: Belumosudil 200 mg BID | Duration of Response (DOR) | 10.9 weeks |
| Cohort 3: Belumosudil 400 mg QD | Duration of Response (DOR) | 15.9 weeks |
Secondary
Failure-free Survival (FFS)
Failure-free survival was defined as the time (in months) from first dose of study drug to either the start of another new systemic treatment for cGVHD, relapse of the underlying disease or death. If no such events happened, FFS was censored by last response assessment or long term follow up assessment, whichever was the latest and available. Kaplan-Meier survival method was used for the analysis.
Time frame: From first dose of study drug to either start of another new systemic treatment for cGVHD, relapse of the underlying disease or death or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Failure-free Survival (FFS) | 10.6 months |
| Cohort 2: Belumosudil 200 mg BID | Failure-free Survival (FFS) | 9.8 months |
| Cohort 3: Belumosudil 400 mg QD | Failure-free Survival (FFS) | 9.7 months |
Secondary
Number of Participants With Best Overall Response (BOR)
BOR was defined as the participants with either a CR or PR or lack of response (LOR), where LOR included the response status of unchanged (LOR-U), mixed (LOR-M), or progression (LOR-P). BOR was assessed per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria. CR was defined as the resolution of all manifestations in each organ or site; PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; LOR-M was defined as CR or PR in at least one organ accompanied by progression in another organ, LOR-U was defined as outcomes that did not meet the criteria for CR, PR, progression or mixed response, LOR-P was defined as progression in at least one organ or site without a response in any other organ or site.
Time frame: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Best Overall Response (BOR) | CR | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Best Overall Response (BOR) | LOR-P | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Best Overall Response (BOR) | LOR-M | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Best Overall Response (BOR) | LOR-U | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Best Overall Response (BOR) | PR | 11 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Best Overall Response (BOR) | LOR-U | 3 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Best Overall Response (BOR) | LOR-M | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Best Overall Response (BOR) | LOR-P | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Best Overall Response (BOR) | CR | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Best Overall Response (BOR) | PR | 11 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Best Overall Response (BOR) | PR | 12 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Best Overall Response (BOR) | CR | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Best Overall Response (BOR) | LOR-U | 4 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Best Overall Response (BOR) | LOR-P | 1 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Best Overall Response (BOR) | LOR-M | 0 Participants |
Secondary
Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage
Calcineurin inhibitors included systemic tacrolimus and cyclosporine. Number of participants who took CNI at Baseline and had reduction and discontinuation in CNI use as compared to Baseline during the study are reported in this outcome measure. EOT visit was performed within 3 days after the participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication.
Time frame: Baseline up to end of treatment (i.e., anytime up to 64.2 months)
Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants who had taken CNI at Baseline and with available data for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage | Participants with reduction in CNI dose | 5 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage | Participants who discontinued CNI | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage | Participants with reduction in CNI dose | 5 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage | Participants who discontinued CNI | 1 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage | Participants with reduction in CNI dose | 6 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage | Participants who discontinued CNI | 3 Participants |
Secondary
Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment
The GSR assessment was performed by asking the participants to rate their disease severity of cGVHD symptoms on a 0 to 10-point numeric rating scale, where score 0 indicated 'not at all severe cGVHD symptoms' and score 10 indicated 'most severe cGVHD symptoms possible'. The response was defined using scores from 9 organs: skin, eyes, mouth, esophagus, upper gastrointestinal (GI) track, lower GI tract, liver, lungs, and joints and fascia plus GSR. End of treatment (EOT) visit was performed within 3 days after participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. Maximal improvement from Baseline was calculated as lowest GSR score on scheduled visits minus GSR score at Baseline with possible ranges from -10 to 10. The lower the number means the better improvement in cGVHD symptoms. Only those categories in which at least 1 participant had data were reported.
Time frame: From Baseline up to end of treatment (i.e., up to 64.2 months)
Population: Analysis was performed on mITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 0 | 5 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -3 | 4 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 3 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -1 | 1 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -2 | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -7 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -5 | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -6 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 1 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -4 | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | Missing | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -2 | 4 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -7 | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -6 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -5 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -4 | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -3 | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -1 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 0 | 4 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 1 | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 3 | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | Missing | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 3 | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 0 | 3 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -5 | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -7 | 2 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | 1 | 1 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -6 | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -2 | 4 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -3 | 1 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | Missing | 3 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -1 | 4 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment | -4 | 3 Participants |
Secondary
Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report
cGVHD symptom severity was self-reported by participants. Participants were asked to rate their disease symptom severity over the last week on the following questions: skin itching at its worst, moth dryness at its worst, mouth pain at its worst, mouth sensitivity at its worst, main compliant on eyes, symptom severity on eyes. Severity rating was done on a 0 to 10-point numeric rating scare, where score 0 indicated 'not at all severe cGVHD symptoms' and score 10 indicated 'most severe cGVHD symptoms possible'. EOT visit was performed within 3 days after participant's last dose of study drug. Baseline value was defined as valid and last non-missing value obtained within 28 days prior to participant receiving first study medication. Maximal improvement from Baseline was calculated as the lowest symptom severity score on scheduled visits minus the symptom severity score at Baseline with possible ranges from -10 to 10. The lower the number means the better improvement in cGVHD symptoms.
Time frame: From Baseline up to end of treatment (i.e., up to 64.2 months)
Population: Analysis was performed on mITT population. Only those categories in which at least 1 participant had data were reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 4 | 1 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 0 | 1 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -3 | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -6 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -1 | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -2 | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -8 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -7 | 3 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 2 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -5 | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | Missing | 2 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 1 | 0 Participants |
| Cohort 1: Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -4 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -2 | 3 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -8 | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -7 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -6 | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -5 | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -4 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -3 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -1 | 2 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 0 | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 1 | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 2 | 1 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 4 | 0 Participants |
| Cohort 2: Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | Missing | 2 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 0 | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -5 | 2 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 4 | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 1 | 1 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -6 | 4 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -8 | 1 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | 2 | 2 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -2 | 2 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -3 | 2 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -7 | 0 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -1 | 2 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | -4 | 1 Participants |
| Cohort 3: Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report | Missing | 4 Participants |
Secondary
Overall Survival (OS)
Overall survival was defined as the time (in months) from first dose of study drug to the death due to any reason. If there was no death, OS was censored by last visit, last long-term follow-up, or study cut-off date, whichever occurred first. Kaplan-Meier survival method was used for the analysis.
Time frame: From first dose of study drug to date of death from any cause or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Overall Survival (OS) | NA months |
| Cohort 2: Belumosudil 200 mg BID | Overall Survival (OS) | NA months |
| Cohort 3: Belumosudil 400 mg QD | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants With Best Response in Each Individual Organ
Best response was defined as the percentage of participants with CR or PR. Response was assessed per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria; CR was defined as the resolution of all manifestations in each organ or site; PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site. Organ response assessment was performed on 9 individual organs: skin, eyes, mouth, esophagus, upper gastrointestinal (GI), lower GI, liver, lungs, and joints and fascia and is reported in this outcome measure.
Time frame: From date of randomization until disease progression or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. Here, '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Joints and Fascia | 54.5 percentage of participants |
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Lower GI tract | 0 percentage of participants |
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Esophagus | 50.0 percentage of participants |
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Upper GI tract | 100.0 percentage of participants |
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Eyes | 35.7 percentage of participants |
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Skin | 23.1 percentage of participants |
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Lungs | 0 percentage of participants |
| Cohort 1: Belumosudil 200 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Mouth | 46.2 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Upper GI tract | 100.0 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Skin | 16.7 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Eyes | 36.4 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Mouth | 45.5 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Lower GI tract | 100.0 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Liver | 50.0 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Lungs | 0 percentage of participants |
| Cohort 2: Belumosudil 200 mg BID | Percentage of Participants With Best Response in Each Individual Organ | Joints and Fascia | 45.5 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Lower GI tract | 0 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Skin | 13.3 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Eyes | 23.5 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Joints and Fascia | 41.7 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Esophagus | 25.0 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Upper GI tract | 50.0 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Mouth | 45.5 percentage of participants |
| Cohort 3: Belumosudil 400 mg QD | Percentage of Participants With Best Response in Each Individual Organ | Lungs | 30.0 percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2)
Cmax was the maximum observed plasma concentration, obtained by a non-compartmental analysis. Cmax data for Belumosudil and its metabolites KD025m1 and KD025m2 are reported in this outcome measure.
Time frame: Cycles 1 and 2: pre-dose (0 hour), 1, 2, 3, 4, 5, and 6 hours post-dose on Day 1
Population: Analysis was performed on PK population which included all participants who received at least one dose of study drug and had at least 1 post-dose PK sample drawn. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 2500 nanograms per milliliter | Geometric Coefficient of Variation 60.1 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 2020 nanograms per milliliter | Geometric Coefficient of Variation 101 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 44.4 nanograms per milliliter | Geometric Coefficient of Variation 67.9 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 36.2 nanograms per milliliter | Geometric Coefficient of Variation 43 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 208 nanograms per milliliter | Geometric Coefficient of Variation 93.1 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 158 nanograms per milliliter | Geometric Coefficient of Variation 150 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 145 nanograms per milliliter | Geometric Coefficient of Variation 147 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 1400 nanograms per milliliter | Geometric Coefficient of Variation 98.5 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 45.0 nanograms per milliliter | Geometric Coefficient of Variation 38.6 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 99.2 nanograms per milliliter | Geometric Coefficient of Variation 112 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 1890 nanograms per milliliter | Geometric Coefficient of Variation 120 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 34.8 nanograms per milliliter | Geometric Coefficient of Variation 58.8 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 3270 nanograms per milliliter | Geometric Coefficient of Variation 63 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 63.9 nanograms per milliliter | Geometric Coefficient of Variation 59.4 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 265 nanograms per milliliter | Geometric Coefficient of Variation 154 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 55.8 nanograms per milliliter | Geometric Coefficient of Variation 82.1 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 2960 nanograms per milliliter | Geometric Coefficient of Variation 69.7 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 388 nanograms per milliliter | Geometric Coefficient of Variation 82.3 |
Secondary
Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2)
AUC0-6hr was defined as area under the plasma concentration versus time curve from time 0 to 6 hours post-dose, obtained by a non-compartmental analysis from the concentration-time data. AUC0-6hr data for Belumosudil and its metabolites KD025m1 and KD025m2 are reported in this outcome measure.
Time frame: Cycles 1 and 2: pre-dose (0 hour), 1, 2, 3, 4, 5, and 6 hours post-dose on Day 1
Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 8350 hours*nanograms per milliliter | Geometric Coefficient of Variation 60.3 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 7090 hours*nanograms per milliliter | Geometric Coefficient of Variation 95.9 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 140 hours*nanograms per milliliter | Geometric Coefficient of Variation 72.3 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 123 hours*nanograms per milliliter | Geometric Coefficient of Variation 38.2 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 565 hours*nanograms per milliliter | Geometric Coefficient of Variation 90.8 |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 471 hours*nanograms per milliliter | Geometric Coefficient of Variation 145 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 513 hours*nanograms per milliliter | Geometric Coefficient of Variation 122 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 4960 hours*nanograms per milliliter | Geometric Coefficient of Variation 108 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 160 hours*nanograms per milliliter | Geometric Coefficient of Variation 31.3 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 282 hours*nanograms per milliliter | Geometric Coefficient of Variation 125 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 7190 hours*nanograms per milliliter | Geometric Coefficient of Variation 115 |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 114 hours*nanograms per milliliter | Geometric Coefficient of Variation 60.8 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 12000 hours*nanograms per milliliter | Geometric Coefficient of Variation 68.8 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 216 hours*nanograms per milliliter | Geometric Coefficient of Variation 61.9 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 923 hours*nanograms per milliliter | Geometric Coefficient of Variation 144 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 178 hours*nanograms per milliliter | Geometric Coefficient of Variation 72.9 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 11500 hours*nanograms per milliliter | Geometric Coefficient of Variation 97.3 |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: The Area Under the Plasma Concentration Versus Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6hr) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 1150 hours*nanograms per milliliter | Geometric Coefficient of Variation 97.1 |
Secondary
Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2)
Tmax was defined as time to reach maximum observed plasma concentration, obtained by a non-compartmental analysis. Tmax data for Belumosudil and its metabolites KD025m1 and KD025m2 are reported in this outcome measure.
Time frame: Cycles 1 and 2: pre-dose (0 hour), 1, 2, 3, 4, 5, and 6 hours post-dose on Day 1
Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 2.12 hours |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 2.53 hours |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 2.50 hours |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 2.98 hours |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 2.82 hours |
| Cohort 1: Belumosudil 200 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 2.98 hours |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 2.00 hours |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 3.43 hours |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 2.05 hours |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 3.00 hours |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 2.47 hours |
| Cohort 2: Belumosudil 200 mg BID | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 1.75 hours |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 2 Day 1 | 2.66 hours |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 1 Day 1 | 1.98 hours |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 2 Day 1 | 3.03 hours |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m1: Cycle 2 Day 1 | 2.17 hours |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | Belumosudil: Cycle 1 Day 1 | 3.03 hours |
| Cohort 3: Belumosudil 400 mg QD | Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Belumosudil and Its Metabolites (KD025m1 and KD025m2) | KD025m2: Cycle 1 Day 1 | 2.98 hours |
Secondary
Time to Next Therapy (TTNT)
The TTNT was defined as the time (in months) from first treatment to the time of new systemic cGVHD treatment. TTNT was censored by last response assessment or long term follow up assessment, whichever was earlier. Kaplan-Meier survival method was used for the analysis.
Time frame: From time of first treatment to the time of new systemic cGVHD treatment or long term follow-up assessment, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Time to Next Therapy (TTNT) | 15.2 months |
| Cohort 2: Belumosudil 200 mg BID | Time to Next Therapy (TTNT) | 9.8 months |
| Cohort 3: Belumosudil 400 mg QD | Time to Next Therapy (TTNT) | 14.2 months |
Secondary
Time-to-Response (TTR)
Time-to-response was measured as the time (in weeks) from first dose of study drug to the time of first documentation of response. Response was defined as the participants achieving a PR or CR at any post-baseline response assessment. Per the 2014 NIH Consensus Development Project for Clinical Trials in cGVHD criteria; CR was defined as the resolution of all manifestations in each organ or site and PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.
Time frame: From first dose of study drug treatment to the time of first documentation of response or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)
Population: Analysis was performed on responder population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Belumosudil 200 mg QD | Time-to-Response (TTR) | 8.14 weeks |
| Cohort 2: Belumosudil 200 mg BID | Time-to-Response (TTR) | 8.14 weeks |
| Cohort 3: Belumosudil 400 mg QD | Time-to-Response (TTR) | 8.07 weeks |