Clinical trial NCT04930562
Conditions: GVHD, Chronic
Sponsor: BioNova Pharmaceuticals (Shanghai) LTD.
Start date: 2021-04-27; Completion date: 2022-12-10
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase 2, open-label, multicenter trial to evaluate the efficacy and safety of BN101 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least First Line of systemic therapy.

Detailed description:
Approximately 30 subjects will be enrolled to receive orally administered BN101 200 mg QD (once daily)

Study drug will be administered in 28-day cycles until disease progression or unacceptable toxicity. Subjects may receive study drug in the inpatient or outpatient setting.

Curative Effect analysis The efficacy was analyzed based on MITT The point estimate and 95%CI of ORR were calculated based on the exact probability method of binomial distribution.If applicable, a logistic regression model will be used for multivariate analysis.

Descriptive statistical analyses were provided for all secondary efficacy endpoints.

The following subgroups will be analysed:

* Severe cGVHD (Yes/No)
* Number of organs involved (\<4 vs. ≥4)
* Number of previous systemic cGVHD treatment (1 vs. ≥2)
* Duration of cGVHD before inclusion (i.e., from the time of cGVHD diagnosis to the time of inclusion)
* Lung Involvement (Yes/No)

Arms: arm 1: 200mg qd po.
Interventions: intervention 1: BN101
Intervention descriptions: intervention 1: BN101 is an orally ROCK2 selective inhibitor

Protocol documents:
Prot_002.pdf: 
 
 
Official Title：The Synopsis of BN101-201 Protocol 
NCT number：NCT04930562 
Document date：25Feb2022 
Version number：3.0 
 
 


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CLINICAL STUDY PROTOCOL 
 
A Phase 2, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of 
BN101/belumosudil in Subjects with Chronic Graft Versus Host Disease 
(cGVHD) After at Least 1 Prior Line of Systemic Therapy 
 
Protocol Number： 
BN101-201 
Version： 
3.0 
Version Date： 
25 Feb 2022 
 
Sponsor： 
BK Pharmaceuticals Ltd. 
Agent： 
BioNova Pharmaceuticals (Shanghai) Ltd. 
Sponsor Contact： 
Yu Wang 
Sponsor Contact 
information： 
Telephone：186 2188 9377  
E-mail: yu.wang@bionovapharma.com 
 
 
Confidentiality Statement 
The ownership of all information contained in this protocol is vested in the sponsor and its agents, and 
therefore, it is provided only for review by the investigator, co-investigators, ethics committees, and 
supervisory and regulatory authorities, and other relevant healthcare organizations. Without the written 
approval of the sponsor and its agents, it is strictly prohibited to communicate any information to third 
parties unrelated to this study, except for the necessary explanations when signing informed consent 
with potential subjects. 
 


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Protocol Signature Page 
（Sponsor） 
I agree： 
 
Conduct this trial in strict accordance with the protocol, the current International 
Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP), and the China 
National Medical Products Administration (NMPA) GCP Guidelines, as well as 
applicable regulations and guidelines. 
 
Responsible for initiating, applying for, organizing and funding this clinical trial, and 
conducting the audit of the clinical trial. 
I have read the full text of this protocol and agree with all the provisions listed in the 
protocol. 
 
Sponsor：BK Pharmaceuticals Ltd. 
Agent：BioNova Pharmaceuticals (Shanghai) Ltd. 
Project Lead of the Agent：Ye Hua, MD, MPH 
Signature 
Date 
 
 
 
 


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Protocol Signature Page 
（Study leading site） 
 
I agree： 
 
Conduct this trial in strict accordance with the protocol, the current ICH GCP, and the 
China NMPA GCP Guidelines, as well as applicable regulations and guidelines. 
 
Keep all data information provided by the sponsor in accordance with confidentiality 
requirements, and when such data information is to be presented to the Ethics Committee 
(IEC), it must be marked as confidential. 
I have read the full text of this protocol and agree with all the provisions listed in the 
protocol. 
 
 
Study Leading Site：The First Affiliated Hospital of Soochow University 
Principal Investigator：Depei Wu 
Signature 
Date 
 
 
 
 
 
 
 
 
 


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Protocol Signature Page（Study site） 
 
Protocol 
Number： 
BN101-201 
Protocol 
Version/Date： 
3.0/ 25 Feb 2022 
Protocol Title： 
 
A Phase 2, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of 
BN101/belumosudil in Subjects with Chronic Graft Versus Host Disease (cGVHD) 
After at Least 1 Prior Line of Systemic Therapy 
Site Number： 
 
 
Investigator
： 
 
 
Study Site： 
 
 
 
I have fully read the clinical study protocol and understand its requirements. I agree to follow the 
protocol and timeline for the conduct of this clinical study. Modifications to the protocol that are not 
approved by the sponsor and/or contract research organization (CRO), and the IEC are considered to 
be contrary to the protocol. 
I agree to conduct the trial in accordance with current ICH GCP and NMPA GCP guidelines and 
applicable regulations and guidelines, and to accept monitoring/auditing of the clinical trial by the 
sponsor and/or CRO, and verification/inspection by the drug regulatory authorities. 
I agree to apply only the trial supplies including the study drug as specified in the protocol. 
 
 
Signature of Principal Investigator 
Name in block letters 
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 


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Sponsor and Agent 
Sponsor 
BK Pharmaceuticals Ltd. 
Agent 
BioNova Pharmaceuticals (Shanghai) Ltd. 
Project Lead of the 
Agent： 
Yu Wang, MD, MS 
Address 
2889 Jinke Road, Chamtime Plaza Building B,9F,Suite 
905, Pudong new district, Shanghai,China 
Zip Code 
201203 
Telephone：186 2188 9377 
E-mail: yu.wang@bionovapharma.com 
 
 
 


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Protocol Synopsis 
Protocol Number 
BN101-201 
Study Title 
A Phase 2, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of 
BN101/belumosudil in Subjects with Chronic Graft Versus Host Disease (cGVHD) After at 
Least 1 Prior Line of Systemic Therapy 
Version 
number/Date 
3.0/ 25 Feb, 2022 
Sponsor 
BK Pharmaceuticals Ltd. 
Agent 
BioNova Pharmaceuticals (Shanghai) Ltd. 
Phase 
II 
Indication 
Subjects with Chronic Graft Versus Host Disease (cGVHD) After at Least 1 Prior Line of 
Systemic Therapy 
Study Objectives 
Primary Objective 
• 
To evaluate the efficacy and safety of BN101/belumosudil in subjects with cGVHD who 
had previously been treated with at least 1 prior line of systemic therapy. 
Secondary Objectives 
• 
To evaluate the PK profile of BN101/belumosudil in subjects with cGVHD who had 
previously been treated with at least 1 prior line of systemic therapy; 
• 
To evaluate other efficacy endpoints of BN101/belumosudil in subjects with cGVHD 
who had previously been treated with at least 1 prior line of systemic therapy. 
Exploratory Objective 
 
To evaluate changes in the Patient-Reported Outcomes (PRO) Measurement Information 
System (PROMIS) Global Health sub-scores of physical and mental functioning  
Study Design 
This study is a multicenter, open, single-arm phase II clinical trial to enroll 30 patients 
with cGVHD who have undergone at least 1 but not more than 5 lines of systemic therapy, 
and to evaluate the efficacy, safety, and PK characteristics of BN101/belumosudil in Chinese 
patients with cGVHD. 
Eligible subjects after signing informed consent form will be enrolled to receive 
BN101/belumosudil (every 28-day cycle) until cGVHD progression, intolerable toxicity, 
initiation of a new cGVHD therapy, recurrence of hematological neoplasm, loss to follow-
up, withdrawal of consent, or death, etc., whichever occurred first. For subjects assessed as 


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"Lack of Response - Mixed" and "Lack of Response - Progression"【Evaluated by the 
investigator based on the National Institutes of Health (NIH) Consensus Development 
Project on Criteria for Clinical Trials in cGVHD(2014) diagnosis and staging, and response 
criteria, hereinafter referred to as the NIH Consensus Criteria (2014)】, if the investigator 
believed that these subjects could continue to benefit from treatment with 
BN101/belumosudil, the treatment may be continued after a written application was 
submitted, and approval from the Sponsor's Medical Monitor as well as documentation of 
the subject's willingness to continue treatment was obtained. For subjects who did not 
achieve any response after 12 cycles of BN101/belumosudil treatment during the main 
study(the end of the main study is defined in section 3.5 of the main body), they should 
discontinue the investigational product treatment and withdraw from the study if they were 
judged by the investigator to have no clinical benefit (e.g., improvements in organ score, 
improvements in Lee symptom scores, reductions of corticosteroid/tacrolimus doses).  
The primary efficacy endpoint was the subject's overall response rate (ORR), which was 
assessed according to the NIH Consensus Criteria (2014) at each of the protocol-specified 
visit viewpoints, and then the ORR was calculated. 
Number of 
Subjects 
This study is an open, single-arm trial with the purpose of bridging Chinese cGVHD 
patients to the US registry study (KD025-213) to assess whether BN101/belumosudil 
treatment of Chinese versus Caucasian cGVHD patients is concordant in terms of efficacy, 
safety, and PK characteristics, the sample size of the trial is not determined by statistical 
assumptions. This study is planned to enroll 30 patients with cGVHD who have undergone 
at least 1 but not more than 5 lines of systemic therapy, and such a sample size is considered 
to be sufficient to meet the needs of assessment with the purpose of bridging. 
Number of Study 
Centers 
Approximately 6~9 
Study duration 
Approximately 2 years 
Study Population 
Inclusion Criteria 
Subjects who met all of the following conditions could be enrolled in the study: 
(1) Male or female subjects aged ≥ 18 years who have had allogeneic hematopoietic 
stem cell transplant (allo-HSCT). 
(2) Have persistent cGVHD manifestations and systemic therapy is indicated. 
(3) Previously received at least 1 and not more than 5 lines of systemic therapy for 
cGVHD. 
(4) Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to 


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screening; or 4 weeks of prednisone or equivalent doses of other corticosteroids at 
doses > 0.5 mg/kg/day with persistent manifestations of cGVHD and no 
improvement; or 2 attempts to reduce the hormone to a lower dose level fail and 
the prednisone dose still needs to be increased to > 0.25 mg/kg/day or an equivalent 
dose. 
(5) Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0 to 
1. 
(6) Life expectancy of more than 12 months. 
General Criteria 
(7) Female subjects of childbearing potential have a negative serum pregnancy test at 
screening. Females of childbearing potential are defined as sexually mature 
females without prior hysterectomy or who have had any evidence of menses in 
the past 12 months.  However, females who have been amenorrheic for 12 or more 
months are still considered to be of childbearing potential if the amenorrhea is 
possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression. 
(8) Sexually active females 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: 
• 
Intra-uterine contraceptive device plus 1 barrier method; 
• 
Stable doses of hormonal contraception (e.g., oral, injectable, subcutaneously 
implanted, transdermal) for at least 3 months plus 1 barrier method; 
• 
Two 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. 
(9) For male subjects who are sexually active and who are partners of females of 
childbearing potential: must agree to use 2 recognized methods of contraception 
during the treatment period and for 3 months after the last dose of study drug (see 
criterion 8 above). 
(10) Subject (or the subject's legally authorized representative) must be fully informed 
of the study contents and is able to provide written ICF prior to any study-specific 
procedures, and is willing to follow the treatment regimen and visit schedule. 
Exclusion Criteria 
Subjects who met any of the following conditions would be excluded from the study: 


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(1) Received a systemic investigational cGVHD treatment within 28 days of study 
entry, but prior treatment is allowed with a washout of at least 28 days or 5 half-
lives.[Note: Corticosteroids, CNIs, sirolimus, mycophenolate mofetil (MMF), 
methotrexate, azathioprine, and in vitro photochemotherapy (ECP) are acceptable 
and subjects must have been on a stable dose/regimen of these for at least 2 weeks 
prior to screening]. 
(2) Recurrence of hematologic tumor (according to criteria for recurrence of the 
corresponding primary hematologic tumor) or post-transplant lymphoproliferative 
disease at screening. 
(3) Current treatment with ibrutinib (except for ibrutinib with a washout of at least 28 
days prior to the first dose of the investigational product). 
Laboratory Tests 
(4) Absolute neutrophil count (ANC) < 1.5 × 109/L. 
(5) Platelet count < 50 × 109/L. 
(6) Alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN), aspartate 
aminotransferase (AST) > 3 × ULN 
(7) Total bilirubin (TBIL) > 1.5 × ULN. 
(8) Creatinine clearance (CrCl) < 60 mL/min (Cockcroft-Gault formula). 
General Criteria 
(9) Pregnant or lactating women. 
(10) History of severe illness, or other evidence of severe illness, or any other conditions 
that would make the subject, in the opinion of the investigator, unsuitable for the 
study  
• 
History of severe [New York Heart Association (NYHA) functional class III 
or IV] cardiovascular disorder, including but not limited to ventricular 
arrhythmias requiring clinical intervention, uncontrolled hypertension 
(systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 
mmHg); unstable angina pectoris, acute coronary syndrome, congestive 
cardiac failure, stroke, or other ≥ Grade 3 cardiac events within 6 months prior 
to enrollment; and NYHA functional class ≥ II or left ventricular ejection 
fraction (LVEF) < 50% by cardiac ultrasound at screening. 
• 
Inability to take oral medications, severe (NCI CTCAE v5.0≥ Grade 3) 
chronic gastrointestinal dysfunction, malabsorption syndrome, or any other 
condition that affects gastrointestinal absorption. 
• 
History of clear neurological or mental disorders (including epilepsy or 


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dementia), current mental disorders, or poor compliance that rendered the 
subject ineligible for participation in the study as judged by the investigator. 
• 
History of other serious (NCI CTCAE v5.0≥ Grade 3) systemic disease that 
rendered the subject ineligible for participation in the clinical trial as judged 
by the investigator. 
(11) Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or 
human immunodeficiency virus (HIV) infection. [Note: Active HBV infection is 
defined as positive for serum hepatitis B virus surface antigen (HBsAg) and/or 
hepatitis B virus e antigen (HBeAg), or HBV-DNA; subjects with positive hepatitis 
B virus core antibody (anti-HBc) should be confirmed for HBV-DNA, and subjects 
who are confirmed to be negative for HBV-DNA could be enrolled; active HCV 
infection is defined as positive for HCV-RNA, and subjects who are positive for 
hepatitis C virus antibody (HCV-Ab) could only be enrolled after confirmed to be 
negative for HCV-RNA. Positive is defined as ＞ the ULN]. 
(12) Diagnosed with another primary malignancy(other than malignancy for which 
allo-HSCT was performed) within 3 years of enrollment, with the exception of: 
• 
Completely resected basal cell or squamous cell carcinoma of the skin; 
• 
Surgically cured carcinoma in situ of the cervix; 
• 
Resected breast ductal carcinoma in situ; 
• 
Prostate cancer with Gleason score < 6 and stable prostate-specific antigen 
(PSA) over 12 months. 
(13) Known allergy to the active ingredient or excipients of the investigational product, 
or any other selective ROCK2 inhibitors. 
(14) Subjects requiring long-term proton pump inhibitors (e.g., rabeprazole, 
omeprazole) or CYP3A4 inducers (e.g., rifampin, phenobarbital). 
(15) Prolongation of QT interval corrected by the Fridericia's formula (QTcF) of > 450 
ms for males and > 470 ms for females at screening. 
(16) Known alcohol or drug dependence. 
(17) Forced expiratory volume in 1 second (FEV1) ≤ 39% or pulmonary function score 
of 3 at screening. 
(18) Treatment with any investigational agent, device, or procedure, within 28 days (or 
5 half-lives, whichever is longer) prior to enrollment. 
(19) Subjects considered unlikely to adhere to treatment and follow protocol in the 
opinion of the investigator. 


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Criteria for completion of study drug therapy and early termination of study drug 
therapy: 
(1) Completion of study drug therapy 
- Completion of study drug therapy as defined by the protocol; or 
- cGVHD disease progression during treatment 
- Death of the subject 
(2) Early termination of study drug therapy 
Refers to the situation in which an enrolled subject becomes unfit to continue treatment with 
the study drug during the course of the study. Early termination of study drug treatment is 
defined as follows: 
- Recurrence of the subject's hematologic tumor during the course of the trial (according to 
the criteria for recurrence of the corresponding primary hematologic tumor). 
- The subject is discontinued due to an adverse event or serious adverse event that makes 
continuation of study drug treatment inappropriate; or the subject is discontinued due to 
an adverse event or serious adverse event for more than 14 days. 
- The investigator determines that the subject's continued treatment with the study drug may 
pose a potential risk greater than benefit to the subject, including: pregnancy; enrollment 
in the study and discovery that the subject does not meet the study protocol inclusion  
criteria and that continued treatment with the study drug poses a risk greater than benefit 
to the subject; failure to follow the protocol or doctor's orders, unauthorized use of other 
treatments, or failure to take the medication in a timely manner and at a dosage that would 
interfere with the assessment of efficacy and increase potential safety risks. 
- Subject withdraws informed consent/withdraws from the study. 
- Subject lost to follow-up. 
After discontinuation of study medication, subjects will undergo end-of-treatment visits 
and enter a safety follow-up period (including a 28-day follow-up after the last dose and a 
long-term safety follow-up). 
Investigational 
Product 
Investigational product: BN101/belumosudil 
Manufacturer: UPM Pharmaceuticals, Inc. 
Sponsor: BK Pharmaceuticals Ltd. 
Agent: BioNova Pharmaceuticals (Shanghai) Ltd. (The investigational drug was provided by 
the agent free of charge) 


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Ingredients: BN101/belumosudil, microcrystalline cellulose, hydroxypropylmethylcellulose, 
cross-linked sodium carboxymethylcellulose, anhydrous colloidal silicon dioxide, 
magnesium stearate, and Obadiol II (yellow 85F32410) 
Specification: 200 mg (tablets equivalent to 200 mg BN101/belumosudil free base) 
Storage conditions: Keep below 25°C 
Expiry date: 24 months tentatively 
Administration: Oral administration with or within 5 minutes after meals, once a day for 28 
days 
Dose adjustment: If adverse events occur during BN101/belumosudil treatment, the dose can 
be adjusted (see table below). 
Toxicity* 
Dose Adjustment 
≥ 
grade 
3 
hepatotoxicity 
(ALT/AST/TBIL) 
Suspend BN101/belumosudil administration; 
Within 14 days§ Toxicity does not return to ≤ Grade 1 or 
baseline level, then discontinue BN101/belumosudil therapy; 
Within 14 days§ Toxicity returns to ≤ Grade 1 or 
Baseline level, resume BN101/belumosudil administration at 
a reduced dose level [e.g., 200 mg QD → 200 mg once every 
other day (QOD)]; 
If the reduced dose level is administered for one full 
treatment cycle tolerated by the subject without recurrence of 
Grade 1 or greater hepatic function abnormality, return the 
dose to the original level for the following treatment cycle; if 
this toxic reaction recurs after the reduced dose level, 
terminate BN101/belumosudil treatment. 
Other ≥ grade 3 
clinically 
significant 
toxicity associated with 
BN101/belumosudil 
Suspend BN101/belumosudil administration; 
Within 14 days§ Toxicity does not return to ≤ Grade 1 or 
baseline level, then discontinue BN101/belumosudil therapy; 
Within 14 days§ Toxicity returns to ≤ Grade 1 or baseline 
level, then BN101/belumosudil administration is resumed at 
a reduced dose level [e.g., 200 mg QD → 200 mg QOD]; if 
the reduced dose level is administered for a full treatment 
cycle as tolerated by the subject, and there is no recurrence of 
Grade 1 or higher of this abnormality, then the next cycle of 
treatment the dose will be restored to the original level [e.g., 
200 mg QOD → 200 mg QD]; 
If the toxic reaction recurs after administration at a 


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reduced dose level, BN101/belumosudil treatment will be 
discontinued. 
*Severity of toxicity was determined according to NCI CTCAE v5.0. 
§ The maximum time allowed for suspension of BN101/belumosudil administration 
due to toxicity was 14 days, and subjects who discontinued for more than 14 days were 
required to withdraw from the study. 
If a subject can tolerate 1 full cycle of treatment after a BN101/belumosudil dose reduction, 
the dose may be restored to the dose prior to the reduction for the next cycle. 
Control drug 
None 
Research 
treatment and 
blood sampling 
The study consisted of a screening period, a treatment period, and a safety follow-up 
period (including a 28-day follow-up after the last dose and a long-term safety follow-up). 
Subjects who sign informed consent form are screened and eligible subjects will receive 
BN101/belumosudil until cGVHD progression[according to NIH Consensus Criteria 
(2014)], intolerable toxicity, initiation of a new cGVHD therapy, recurrence of hematological 
neoplasm, loss to follow-up, withdrawal of consent, or death, etc., whichever occurred first. 
Response assessments would be performed on Day 1 of Cycles 2 to 5 and every 2 cycles 
thereafter (i.e., Day 1 of Cycles 2, 3, 4, 5, 7, 9, 11, etc.). For subjects assessed as "Lack of 
Response - Mixed" and "Lack of Response - Progression"(see table 3 in the main body of the 
protocol), if the investigator believed that these subjects could continue to benefit from 
treatment with BN101/belumosudil, the treatment may be continued after a written 
application was submitted, and approval from the Sponsor's Medical Director as well as 
documentation of the subject's willingness to continue treatment was obtained until cGVHD 
progression, intolerable toxicity, initiation of a new cGVHD therapy, recurrence of 
hematological neoplasm, loss to follow-up, withdrawal of consent, or death, etc., whichever 
occurred first. For subjects who did not achieve any response after 12 cycles of 
BN101/belumosudil treatment during the main study, they should discontinue the 
investigational product treatment and withdraw from the study if they were judged by the 
investigator to have no clinical benefit. 
Data lock and primary analysis will be performed 6 months after enrollment of the last 
subject. All subjects will continue to be followed up for an additional 6 months after the 
primary analysis as required by the protocol, i.e., the study will end 12 months after 
enrollment of the last subject, and a follow-up analysis will be performed at the end of the 
study. Subjects who have not yet experienced cGVHD progression at the end of the study, 
and in the judgment of the investigator, the benefits of continued dosing outweigh the risks, 
the sponsor will continue to provide BN101/belumosudil medication at no cost until cGVHD 
progression, intolerable toxicity, initiation of a new cGVHD therapy, recurrence of 


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hematological neoplasm, loss to follow-up, withdrawal of consent, or death, etc., whichever 
occurred first; or will need to be withdrawn from this study if, in the judgment of the 
investigator, there is no evidence of clinical benefit. 
Subjects who remain free of disease progression at the time of withdrawal from the 
study or who withdraw from the study for reasons other than adverse events should have the 
dose of BN101/belumosudil tapered every 2 weeks as required by the protocol (e.g., 200 mg 
QD  200 mg QOD  discontinue treatment). 
Subjects who completed or prematurely terminated study drug therapy entered a follow-
up period in which the study center contacted subjects by telephone approximately every 12 
weeks to confirm their survival, any changes in cGVHD therapy, and any antitumor therapy 
until no more subjects were taking study drug. 
The safety assessment begins with the signing of informed consent form until 28 days 
after the last dose of study drug (unless otherwise indicated) and includes changes in physical 
examination, vital signs, laboratory tests, electrocardiograms, echocardiograms (if 
necessary), as well as adverse events, adverse events related to the study drug, and serious 
adverse events. 
In addition, the study will evaluate the PK profile of BN101/belumosudil and its 
metabolites, m1 and m2, in all subjects, and the first 12 subjects will require intensive 
collection of PK blood samples.See Appendix (PK Blood Sample Collection Schedule and 
PK Blood Sample Collection Time Window) for PK blood sample collection. 
Concomitant 
medication and 
concomitant 
therapy 
All comorbid medications or treatments will be documented during the study period. 
Initiation of new systemic cGVHD treatment will be considered as starting a new cGVHD 
treatment and will be considered a failure of BN101/belumosudil treatment. 
- Transient increases in corticosteroid dose (no more than 1 mg/kg/day of prednisone 
equivalent) for treatment of cGVHD episodes will be permitted during the study treatment 
period, provided that the dose is reduced to pre-enrollment levels within 6 weeks. If the dose 
remained elevated for more than 6 weeks, it was considered a BN101/belumosudil treatment 
failure. More than 2 episodes of cGVHD requiring an increase in the dose of corticosteroid 
therapy within the first 6 months of BN101/belumosudil treatment will also be considered a 
BN101/belumosudil treatment failure. 
- Continuation of treatment with calcineurin phosphatase inhibitors (e.g., tacrolimus, 
cyclosporine), 
sirolimus, 
MMF, 
methotrexate, 
azathioprine, 
or 
extracorporeal 
photochemistry (ECP), which have been stabilized at baseline, is permitted during study 
treatment. 
- Local/organ-specific therapy for cGVHD is allowed during study treatment. 
- During study treatment, CYP3A4 inducers (e.g., rifampin, phenobarbital) are 
prohibited, proton pump inhibitors (e.g., rabeprazole, omeprazole) are permitted for short 


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periods of time only (no more than 1 week), and CYP1A2 inhibitors/inducers, CYP3A4 
inhibitors, drugs that prolong the QT/QTc interval should be used with caution (see Appendix 
for details of CYP3A4 and CYP1A2 inhibitors/inducers, and drugs that prolong the QT/QTc 
interval). 
- The use of other systemic therapies for cGVHD (including rituximab, ruxolitinib, 
ibrutinib, etc.) or other clinical trial medications is prohibited during study treatment. 
- Tobacco, alcohol, and caffeinated beverages or foods are prohibited on the day of PK 
sample collection. 
Efficacy 
endpoints 
The primary efficacy endpoint was the Overall Response Rate (ORR, including 
Complete Response [CR] and Partial Response [PR]), assessed according to the NIH 
consensus criteria (2014). 
Secondary efficacy endpoints included median Duration of Response (DOR), Change 
in Lee Symptom Scale Score, Response rate by organ system, Percentage of subjects with 
best efficacy as PR and percentage of subjects with best efficacy as CR, Change in 
corticosteroid dose, Change in CNI dose, Failure-Free Survival (FFS), Overall Survival 
(OS), Change in cGVHD severity based on the Physician-Reported Global cGVHD Activity 
Assessment, and Change in symptom activity based on cGVHD Activity Assessment Patient 
Self-Report. 
Safety Endpoints 
AEs, serious adverse events (SAEs), AEs related to the investigational product, Vital 
signs, Physical examination, Laboratory safety tests, 12-lead electrocardiograms (ECGs), 
etc. 
PK Endpoints 
PK parameters include Cmax, time to peak (Tmax), elimination half-life (T1/2), area under 
the concentration-time curve from time 0 to the time of the last measurable concentration 
(AUC0-t), area under the blood concentration-time curve from initiation of dosing to the 
extrapolated infinite time (AUCinf), apparent clearance (CLz/F), and apparent volume of 
distribution (Vz/F), clearance rate constant (Kel), steady-state trough concentration (Cmin,ss), 
steady-state peak concentration (Cmax,ss), steady-state mean blood concentration (Cav,ss), 
steady-state accumulation ratio expressed as AUC0-t (RAUC1), steady-state accumulation ratio 
expressed as AUCinf (RAUC2), and steady-state accumulation ratio expressed as Cmax (RCmax). 
If the metabolites m1 and m2 of BN101/belumosudil can be detected and characterized, the 
ratios of the molecular weight-adjusted metabolites (m1 and m2) to the prodrug (P) Cmax and 
AUC (AUC0-t, AUCinf) also need to be calculated. 
Exploratory 
Endpoints 
Changes in PROMIS Physical and Mental Functioning Global Health Scores 
End of study 
Data lock and primary analysis will be performed 6 months after enrollment of the last 
subject. All subjects will continue to be followed up for an additional 6 months after the 


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primary analysis as required by the protocol, i.e., the study will end 12 months after 
enrollment of the last subject, and a follow-up analysis will be performed at the end of the 
study. Subjects who have not yet experienced cGVHD progression at the end of the study, 
and in the judgment of the investigator, the benefits of continued dosing outweigh the risks, 
may submit a written request and, upon approval by the sponsor's Medical Director and 
documentation of the subject's willingness to continue the treatment, the sponsor will 
continue to provide BN101/belumosudil medication at no cost until cGVHD progression, 
intolerable toxicity, initiation of a new cGVHD therapy, recurrence of hematological 
neoplasm, loss to follow-up, withdrawal of consent, or death, etc., whichever occurred first. 
Serious adverse events (SAEs), study drug use, and subject survival will continue to be 
collected for subjects who continue to be free of charge while the study drug, 
BN101/belumosudil, is administered at the end of the study. 
The study will end when all subjects stop taking the study drug. 
Statistical 
Analysis 
Sample size: 
Because this study is an open, single-arm trial with the purpose of bridging Chinese 
cGVHD patients to the US registry study (KD025-213) to assess whether 
BN101/belumosudil treatment of Chinese versus Caucasian cGVHD patients is consistent in 
terms of efficacy, safety, and PK characteristics, the sample size of this trial is not determined 
by statistical assumptions. This study is planned to enroll 30 patients with cGVHD who have 
undergone at least 1 but not more than 5 lines of systemic therapy. 
Analysis Sets: 
Modified Intent to Treat (mITT): All subjects who had used the study drug after signing the 
informed consent form for enrollment.  
Safety Set (SS): All subjects who had used the study drug after enrollment and had at least 1 
safety assessment.  
Per Protocol Set (PPS): The PPS was a subset of the mITT, and included all subjects who 
have used the study drug after enrollment and have had at least 1 post-treatment efficacy 
assessment, as well as no major protocol deviations. The exact definition of a major protocol 
deviation and the inclusion criteria for the PPS were finally determined in the data review 
meeting.  
Pharmacokinetic analysis Set (PKS): all subjects who have used the study drug since 
enrollment and have post-administration PK data. 
Demographic and baseline characteristics of subjects were statistically analyzed based 
on mITT. mITT was the primary analysis population for the primary efficacy endpoint and 
PPS was the secondary analysis population. Safety analysis based on SS and PK analysis 
based on PKS. 


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Analysis Methods: 
All statistical analyses were completed using SAS version 9.4 or higher. Specific 
statistical methods are described in the statistical analysis plan. 
Continuous variables were described using mean, standard deviation, median, first 
quartile, third quartile, maximum, and minimum. 
Categorical variables were described using frequencies and percentages. If required, 
95% confidence intervals (95% CI) were calculated for frequencies and percentages. 
Safety Analysis 
Safety analysis was performed based on SS. Adverse events were coded in MedDRA 
(version 20.1 or above). Frequencies and percentages of subjects who experienced adverse 
events during treatment were summarized by system organ classification and preferred 
terminology and presented in tabular form. Adverse events of varying severity (according to 
NCI CTCAE v5.0) were summarized by frequency and tabulated by highest severity and 
correlation with study drug. Descriptively summarize adverse events, serious adverse events, 
adverse events of severity ≥ grade 3 (per NCI CTCAE v5.0), adverse events leading to 
withdrawal from the study, adverse events leading to discontinuation of study treatment, 
adverse events leading to dosage adjustments of the study medication, and adverse 
events/serious adverse events related to the study medication for each of the above 
categories. List subjects with each type of adverse event/serious adverse event and death. 
Descriptive statistics of laboratory test abnormalities and changes in laboratory test 
results of severity ≥3 (according to NCI CTCAE v5.0) before and after treatment with study 
medications are presented in a cross-tabulation. 
Descriptive 
statistics 
of 
vital 
signs, 
physical 
examination, 
and 
12-lead 
electrocardiogram results are presented and listed. 
Efficacy Analysis 
Efficacy analyses based on mITT and PPS, with the results of the mITT analysis as the 
main focus. 
Point estimates of ORR and their 95% CIs are calculated based on the binomial 
distribution exact probability method. multifactorial analysis using logistic regression 
models will also be performed if applicable. 
Descriptive statistical analysis is provided for all secondary efficacy endpoints. 
The following subgroups will be analyzed: 
- Severe cGVHD (yes/no) 
- Number of organs involved (<4 vs. ≥4) 
- Number of treatment lines for prior systemic cGVHD (1 vs. ≥2) 


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- Duration of cGVHD prior to enrollment (i.e., from time of cGVHD diagnosis to time 
of enrollment) 
- Lung involvement (yes/no) 
 Pharmacokinetic analysis 
Mean (Mean±SD) drug-time curves for BN101/belumosudil (and its metabolites m1 
and m2, if applicable) and individual drug-time curves for BN101/belumosudil (and its 
metabolites m1 and m2, if applicable) will be plotted for each subject. Descriptive statistics 
of PK parameters of BN101/belumosudil (and its metabolites m1 and m2, if applicable) in 
Chinese patients with cGVHD, and the statistics of each parameter included the number of 
samples, mean, standard deviation, coefficient of variation, geometric mean, geometric 
standard deviation, geometric coefficient of variation, median, first quartile, third quartile, 
minimum and maximum values. 


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TABLE OF CONTENTS 
PROTOCOL SIGNATURE PAGE ...................................................................................................................... 3 
PROTOCOL SIGNATURE PAGE（STUDY SITE） ............................................................................................ 5 
PROTOCOL SYNOPSIS .................................................................................................................................. 7 
TABLE OF CONTENTS ......................................................................................................................... 20 
LIST OF TABLES .................................................................................................................................... 23 
LIST OF ABBREVIATIONS ................................................................................................................... 24 
1. 
STUDY BACKGROUND .........................................................................................................27 
1.1 
OVERVIEW ................................................................................................................................. 27 
1.2 
RHO-ASSOCIATED PROTEIN KINASES ......................................................................................... 28 
1.3 
BN101/BELUMOSUDIL NON-CLINICAL STUDY ............................................................................ 28 
1.4 
OVERSEAS CLINICAL STUDIES OF BN101/BELUMOSUDIL ........................................................ 30 
1.4.1 Pharmacokinetics ...................................................................................................................................... 30 
1.4.2 Efficacy ....................................................................................................................................................... 31 
1.4.3 Safety ........................................................................................................................................................... 33 
1.5 
BN101-101 STUDY ................................................................................................................... 37 
1.6 
RATIONALE FOR THE DESIGN OF THIS STUDY ........................................................................... 38 
2. 
STUDY OBJECTIVES/PRUPOSE ..........................................................................................39 
3. 
STUDY POPULATION ............................................................................................................39 
3.1 
INCLUSION CRITERIA ................................................................................................................. 39 
3.2 
EXCLUSION CRITERIA ................................................................................................................ 40 
3.3 
CRITERIA FOR COMPLETION OF STUDY DRUG THERAPY AND EARLY TERMINATION OF STUDY DRUG 
THERAPY 
 ................................................................................................................................................... 42 
3.4 
EARLY TERMINATION OF THE STUDY/CLOSURE OF THE RESEARCH CENTER .............................. 44 
3.5 
END OF STUDY ........................................................................................................................... 45 
4. 
STUDY DESIGN .......................................................................................................................45 
4.1 
TYPE OF STUDY AND DESIGN RATIONALE ................................................................................... 45 
4.2 
RANDOMIZATION AND BLINDING ................................................................................................ 47 
4.3 
EXPERIMENTAL PROCEDURES AND PHASES ................................................................................ 47 
4.3.1 Screening/baseline period (-14 days ~ -1 day) .................................................................................... 48 
4.3.2 Cycle 1 ......................................................................................................................................................... 49 
4.3.3 Day 1 of Cycle 2 ~ Cycle N (C2D1 ~ CxD1, time window for the corresponding examination: ±3 
days): 
 
 ...................................................................................................................................................................... 50 
4.3.4 End-of-treatment visit (within 7 days after the last dose or at the end of the main study) ......... 52 
4.3.5 Follow-up 28 days after last dose (±7 days) ....................................................................................... 52 
4.3.6 Long-Term Safety Follow-Up ................................................................................................................ 53 
4.3.7 Unscheduled visits .................................................................................................................................... 53 
4.4 
PHARMACOKINETIC SAMPLE COLLECTION, HANDLING, TRANSPORTATION, AND TESTING ........ 54 
4.4.1 Pharmacokinetic Sample Collection ...................................................................................................... 54 
4.4.2 Pharmacokinetic Sample Handling, Storage and Transportation .................................................... 54 
4.4.3 Pharmacokinetic Sample Assays ............................................................................................................ 54 
5. 
STUDY TREATMENT .............................................................................................................55 
5.1 
NAME OF DRUG, PHYSICAL AND CHEMICAL PROPERTIES, CHARACTER, SPECIFICATION, COMPOSITION, 
USAGE, PACKAGING, STORAGE ........................................................................................................................... 55 
5.1.1 Investigational product ............................................................................................................................ 55 
5.1.2 Control drug .............................................................................................................................................. 55 
5.2 
METHOD OF ADMINISTRATION .................................................................................................... 55 
5.3 
DRUG PACKAGING ...................................................................................................................... 55 
5.4 
DRUG LABELING ........................................................................................................................ 56 
5.5 
DRUG DISTRIBUTION, RECORDING AND RECOVERY ................................................................... 56 
6. 
TREATMENT OF SUBJECTS ................................................................................................57 
6.1 
DOSE ADJUSTMENT.................................................................................................................... 57 
6.2 
MANAGEMENT OF MISSED DOSES .............................................................................................. 58 
6.3 
MANAGEMENT OF OVERDOSE .................................................................................................... 58 


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6.4 
COMBINATIONS OF MEDICATIONS AND TREATMENTS .................................................................. 59 
6.4.1 Corticosteroids .......................................................................................................................................... 59 
6.4.2 Systemic cGVHD Therapies .................................................................................................................. 59 
6.4.3 Topical / Organ Specific Therapies for cGVHD ............................................................................... 59 
6.4.4 Proton Pump Inhibitors .......................................................................................................................... 59 
6.4.5 CYP 3A4 Inhibitors / Inducers ............................................................................................................. 60 
6.4.6 CYP1A2 Inhibitors / Inducers .............................................................................................................. 60 
6.4.7 Drugs Prolonging the QTc Interval ...................................................................................................... 60 
6.4.8 Other Prohibited Combination Medications ....................................................................................... 60 
6.5 
TREATMENT COMPLIANCE ......................................................................................................... 60 
7. 
STUDY ENDPOINTS/INDICATORS .....................................................................................60 
7.1 
EFFICACY ENDPOINTS/INDICATORS ............................................................................................ 60 
7.1.1 Primary efficacy endpoints/indicators .................................................................................................. 61 
7.1.2 Secondary efficacy endpoints/indicators .............................................................................................. 61 
7.1.3 Exploratory Endpoints ............................................................................................................................ 62 
7.2 
SAFETY ENDPOINTS/INDICATORS ............................................................................................... 62 
7.3 
PK ENDPOINTS/INDICATORS ....................................................................................................... 63 
8. 
SAFETY ASSESSMENT ..........................................................................................................63 
8.1 
VITAL SIGNS .............................................................................................................................. 63 
8.2 
PHYSICAL EXAMINATION ............................................................................................................ 64 
8.3 
TWELVE-LEAD ECG ................................................................................................................... 64 
8.4 
CLINICAL LABORATORY PARAMETERS ....................................................................................... 64 
8.5 
PREGNANCY TESTING ................................................................................................................ 65 
8.6 
ADVERSE EVENT ........................................................................................................................ 65 
8.6.1 Definition ................................................................................................................................................... 65 
8.6.2 Collection and reporting procedures ..................................................................................................... 71 
8.7 
DEATH ........................................................................................................................................ 73 
8.7.1 Recording of Deaths ................................................................................................................................ 73 
8.7.2 Reporting of death .................................................................................................................................... 74 
8.8 
HOSPITALIZATION ...................................................................................................................... 74 
8.9 
PREGNANCY ............................................................................................................................... 75 
8.10 
OVERDOSE ................................................................................................................................. 76 
8.11 
RAPID REPORTING OF SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTION BY THE SPONSOR76 
9. 
DATA MANAGMENT ..............................................................................................................77 
9.1 
DATA MANAGEMENT WORKFLOW .............................................................................................. 78 
9.1.1 Workflow.................................................................................................................................................... 78 
9.1.2 Role and Responsibility ........................................................................................................................... 78 
9.2 
DATABASE DESIGN AND CREATION ............................................................................................. 79 
9.3 
DATA ENTRY .............................................................................................................................. 79 
9.4 
DATA VERIFICATION ................................................................................................................... 79 
9.5 
MEDICAL CODING ...................................................................................................................... 79 
10. 
STATISTICAL CONSIDERATIONS ......................................................................................80 
10.1 
GENERAL PRINCIPLES ................................................................................................................ 80 
10.2 
SAMPLE SIZE DETERMINATION ................................................................................................... 80 
10.3 
STATISTICAL ANALYSIS POPULATION ......................................................................................... 80 
10.4 
SUBGROUP ANALYSES ................................................................................................................ 81 
10.5 
DATA ANALYSIS ......................................................................................................................... 81 
10.6 
STATISTICAL ANALYSIS METHODS ............................................................................................. 81 
10.6.1 
Distribution of subjects and baseline characterization ................................................................. 81 
10.6.2 
Efficacy Analyses ................................................................................................................................ 82 
10.6.3 
Safety Analyses .................................................................................................................................... 83 
10.6.4 
Pharmacokinetic Analyses ................................................................................................................. 83 
10.7 
INTERIM ANALYSIS .................................................................................................................... 84 
11. 
CLINICAL TRIAL MANAGEMENT .....................................................................................84 


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11.1 
STATEMENT ................................................................................................................................ 84 
11.2 
ETHICAL ASPECTS ...................................................................................................................... 84 
11.3 
ORIGINAL DATA VERIFICATION .................................................................................................. 85 
11.4 
QUALITY ASSURANCE AND AUDIT ............................................................................................. 85 
11.5 
INFORMED CONSENT FORM ........................................................................................................ 86 
11.6 
PROTOCOL AMENDMENT............................................................................................................ 86 
11.7 
PROTOCOL DEVIATION ................................................................................................................ 87 
11.8 
CASE REPORT FORM .................................................................................................................. 87 
11.9 
MONITOR ................................................................................................................................... 88 
11.10 
INTELLECTUAL PROPERTY.......................................................................................................... 89 
11.11 
SUBJECT PRIVACY ...................................................................................................................... 89 
12. 
PAPER PUBLICATION ...........................................................................................................89 
13. 
STUDY DOCUMENTATION, CRFS, AND RECOD KEEPING .........................................90 
13.1 
ORIGIONAL DOCUMENTS ............................................................................................................ 90 
13.2 
DOCUMENT RETENTION AT CLINICAL CENTER ............................................................................ 90 
13.2.1 
Documents relating to ethics committees ...................................................................................... 90 
13.2.2 
Documents relating to study ............................................................................................................. 90 
13.3 
RETENTION OF DOCUMENTS ON SPONSORS ................................................................................. 91 
14. 
REFERENCES ..........................................................................................................................92 
15. 
APPENDIX ................................................................................................................................94 
APPENDIX 1 SCHEDULE OF ASSESSMENTS .............................................................................................. 94 
APPENDIX 2 PHARMACOKINETICS SAMPLING ....................................................................................... 98 
APPENDIX 3 PHARMACOKINETIC BLOOD SAMPLE COLLECTION TIME WINDOW ............................... 99 
APPENDIX 4 ECG ASSESSMENTS .......................................................................................................... 100 
APPENDIX 5  CGVHD ACTIVITY ASSESSMENT FOR CLINICIAN .......................................................... 101 
APPENDIX 6 CGVHD RESPONSE ASSESSMENT .................................................................................... 107 
APPENDIX 7 CGVHD LEE SYMPTOM SCALE SCORE ........................................................................... 108 
APPENDIX 8  PROMIS GLOBAL HEALTH SCORE ................................................................................ 110 
APPENDIX 9  CGVHD ACTIVITY ASSESSMENT-PATIENT SELF REPORT ............................................ 111 
APPENDIX 10  EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS ....... 113 
APPENDIX 11  CALCULATION FORMULA OF CREATININE CLEARANCE .............................................. 114 
APPENDIX 12  DRUGS THAT INDUCE AND INHIBIT CYP3A4 ................................................................ 115 
APPENDIX 13 DRUGS THAT INDUCE AND INHIBIT CYP1A2 ................................................................ 116 
APPENDIX 14 DRUGS THAT PROLONG QT/QTC .................................................................................. 117 
APPENDIX 15 EQUIVALENT DOSE OF CORTICOSTEROID HORMONE .................................................. 118 
 


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LIST OF TABLES 
Table 1 Treatment Emergent Adverse Events Occurring in ≥5% of Subjects at Any Dose Level 
in Studies of cGVHD (KD025-208 and KD025-213), IPF (KD025-207) or Psoriasis 
(KD025-205, KD025-206, and KD025-211) by System Organ Class and Preferred Term 
(Safety Population) ........................................................................................................................... 34 
Table 2 Plasma BN101/belumosudil pharmacokinetic parameters-PK analysis set ............................. 38 
Table 3 BN101/belumosudil dose adjustment .......................................................................................... 57 
Table 4 cGVHD Response Definitions ...................................................................................................... 60 
Table 5 Clinical Laboratory Tests ............................................................................................................. 63 
Table 6 Determination of causal relationship between adverse events and study drugs ...................... 69 
Table 7 Serious Adverse Event Reporting Units and Contact Information .......................................... 72 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADR 
adverse drug reaction 
AE 
adverse event 
allo-HSCT 
allogeneic-hematopoietic stem cell transplantation 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUC0-t 
area under the plasma concentration-time curve from time zero to the 
last measurable time point 
AUCinf 
area under the blood concentration-time curve from initiation of dosing 
to imputed infinite time 
BID 
twice daily 
BSC 
best supportive care 
Cav,ss 
mean blood concentration of steady state 
cGVHD 
chronic graft versus host disease 
Cmax 
maximum concentration observed 
Cmax,ss 
maximum concentration observed of steady state 
Cmin,ss 
minimal concentration observed of steady state 
CNI 
calcineurin inhibitor 
CLz/F 
apparent total plasma clearance 
CR 
complete response 
CRO 
contract research organization 
CYP 
cytochrome P450 
DLCO 
diffusing capacity of carbon monoxide 
DLT 
dose-limiting toxicity 
DoR 
duration of response 
EC 
ethics committee 
ECOG 
eastern cooperative oncology group 


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Abbreviation 
Definition 
ECP 
extracorporeal photopheresis 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume (in the first second) 
FFS 
failure-free survival 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for/Conference on Harmonization 
ICSR 
Individual case safety reports 
IRB 
Institutional review board 
LR 
Lack of response 
LVEF 
left ventricular ejection fraction 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat 
MMF 
Mycophenolate Mofetil 
NCI CTCAE v5.0 
National Cancer Institute-Common Terminology Criteria for Adverse 
Events 5.0 
NIH 
National Institutes of Health 
NYHA 
New York Heart Association 
ORR 
overall response rate 
OS 
overall survival 
PASI 
Psoriasis Area and Severity Index 


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Abbreviation 
Definition 
PK 
pharmacokinetic 
PKS 
Pharmacokinetic analysis Set 
PPS 
Per Protocol Set 
PR 
partial response 
PROMIS 
Patient-Reported Outcome Measurement Information System 
PS 
Performance Status 
PTE 
pre-treatment event 
QA 
quality assurance 
QD 
once daily 
QOD 
once every other day 
QTcB 
corrected QT interval using Bazetts's formula 
QTcF 
corrected QT interval using Fridericia's formula 
ROCK 
Rho-associated protein kinase 
RV 
residual volume 
SAE 
serious adverse event 
SS 
safety set 
SUSAR 
suspected unexpected serious adverse event 
TBIL 
total bilirubin 
Tfh 
T follicular helper 
Th17 
T-helper 17 
TLC 
total lung capacity 
Tmax 
observed time to reach peak plasma concentration 
Tregs 
regulatory T cell 
T1/2 
half-life 
ULN 
upper limit of normal 
Vz/F 
apparent volume of distribution 
95%CI 
95% confidence interval 
 


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1. STUDY BACKGROUND 
1.1 
Overview 
Although gene therapy and cellular therapy (e.g., CAR-T) are increasingly being used to treat 
hematologic malignancies, the complications associated with these therapies and the long-term 
prognosis of most postoperative patients make allogeneic hematopoietic stem cell transplantation 
(allo-HSCT), a potentially curative treatment for hematologic neoplasms, one of the most desirable 
treatments for malignant hematologic neoplasms for today's patients and physicians, and with the 
widespread use of peripheral blood stem cell transplantation of human leukocyte antigen-
incompatible (HLA)-identical siblings and unrelated donors in the clinic, the number of clinical 
cases of allo-HSCT is constantly on the rise[1]. 
Chronic graft versus host disease (cGVHD) remains a major complication of allo-HSCT 
involving multiple organs and occurring in up to 70% of transplant recipients depending upon 
donor and transplant characteristics[2]. Multicenter and registry data show a cumulative incidence 
of 30% to 50%[3,4]. Patients with cGVHD require prolonged immunosuppressive treatment for an 
average of 2 to 3 years from the initial diagnosis, with 10% of those surviving for at least 7 years 
still requiring immunosuppressive treatment at that time and beyond[5],the disease has become a 
major cause of long-term survival and quality of life in post-transplant patients[1]. 
Glucocorticoids, with or without calcineurin inhibitors, remain the standard initial treatment, 
but are associated with significant side effects and unsatisfactory outcomes, particularly for 
patients with high-risk features of cGVHD[6].Therefore, the exploration of new systemic therapies 
for cGVHD is still a hot research topic. 
Ibrutinib (IMBRUVICA) was approved by the FDA for the treatment of adult patients with 
cGVHD after failure of one or more lines of systemic therapy based upon data from an open-label 
study (Study 1129; NCT02195869) of 42 subjects with cGVHD who had failed first line 
corticosteroid therapy and most patients with little organ involvement, the overall response rate 
(ORR) after treatment reached 67%, and based on the results of this study, the US FDA approved 
the indication of ibrutinib in August 2017 for the 2-line systemic treatment of cGVHD. Although 
ibrutinib has demonstrated good efficacy in cGVHD, 24% of subjects in this clinical study 
discontinued treatment due to adverse events (AEs) related to the study drug [7], and the incidence 
of AEs such as hemorrhage, infection, and atrial fibrillation caused by this class of BTK-inhibiting 
drugs is also high, which affects the long-term safety of patients taking. 
In China, a second-line cGVHD indication for ibrutinib has not been approved. Currently, 
there is no approved standard second-line treatment for cGVHD, except for first-line corticosteroid 


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systemic therapy, which is the systemic standard of care for cGVHD. Thus, there is an unmet 
clinical need in this disease area. 
1.2 
Rho-Associated Protein Kinases 
ROCKs are members of the serine/threonine kinase family, often studied for their role in cell 
morphology, motility, and shape through effects on the cytoskeleton[9,10]. Two ROCK isoforms 
have been identified, ROCK1 and ROCK2. While both are involved in Rho-mediated changes in 
the actin/myosin cytoskeletal network, ROCK1 and ROCK2 are not redundant signaling molecules 
and may serve different functions within cells[11,12,13]. Recent research has uncovered additional 
roles for ROCK signaling, in conditions including autoimmune disease[14] aggravated or caused by 
a Th17-polarized T cell response and pulmonary fibrosis[15]. Rho guanosine triphosphate 
(GTP)ase-mediated signaling pathways play a central role in coordinating and balancing T cell 
mediated immune responses, including T cell receptor-mediated signaling, cytoskeletal 
reorganization, and the acquisition of the appropriate T cell effector program [16]. 
Studies have demonstrated that aberrant activation of ROCK2 leads to induction of interleukin 
(IL)-17 and IL-21 via interferon regulatory factor 4 (IRF4)-dependent mechanism [17]. In addition, 
ROCK activity was found to be up-regulated in patients with rheumatoid arthritis (RA) and 
systemic lupus erythematosus[18], and inhibition of ROCK2 effectively decreased IL-17 production 
in vivo and demonstrated efficacy in arthritis and lupus mouse models. Autoimmunity also 
involves alterations to regulatory T cells that suppress activation of the immune system and play a 
critical role in maintaining immunological tolerance to self-antigens and inhibiting autoimmune 
responses [19]. ROCK2 inhibition may increase the suppressive function of regulatory T cells. 
Therefore, specific inhibition of ROCK2 is used in the treatment of autoimmune diseases. 
1.3 
BN101/belumosudil Non-clinical study 
Kadmon Corpration, LLC. (hereinafter referred to as Kadmon) has now completed a non-
clinical evaluation of BN101/belumosudil(i.e., KD0251), summarized as follows. 
Non-clinical pharmacological studies suggest that BN101/belumosudil may be of therapeutic 
benefit in a variety of indications, particularly for autoimmune and fibrotic diseases. In vitro, 
BN101/belumosudil has demonstrated an impact on the T-helper 17 (Th17) as well as on the 
actin/myosin cytoskeletal network and collagen formation. In vivo, BN101/belumosudil has 
demonstrated efficacy in a variety of clinically relevant animal models of disease including 
 
 
1 The former code for BN101 was KD025, and since the code used for the overseas clinical trial was KD025, the use of the former 
code KD025 has been retained for parts of this protocol. 


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cGVHD, diffuse cutaneous systemic sclerosis (dcSSc), idiopathic pulmonary fibrosis (IPF), and 
other autoimmune diseases. 
BN101/belumosudil plasma exposures in nonclinical animal species generally increased with 
dose, were dose proportional or greater than dose proportional, and showed some accumulation. The 
elimination half-life of belumosudil was variable in nonclinical studies with values of approximately 
2 hours in mouse, 1-7 hours in rat and rabbit, and 1-3 hours in dog. BN101/belumosudil undergoes 
first pass metabolism in all evaluated species after oral administration to form a ROCK2 active 
metabolite, BN101/belumosudil m1(minor human metabolite), and a metabolite that is relatively less 
active against ROCK2, BN101/belumosudil m2(major human metabolite). 
Distribution studies demonstrated BN101/belumosudil distribution primarily into tissues 
associated with elimination (GI, liver, kidney, urinary bladder), adrenal gland, and exocrine 
glandular tissue. BN101/belumosudil has some affinity for melanin. BN101/belumosudil excretion 
was via the faecal route (~90%). BN101/belumosudil and BN101/belumosudil m1 are > 99% bound 
to human, dog and rat plasma proteins; BN101/belumosudil m2 is > 99% bound to human plasma 
protein. 
Based on in-vitro assessment, CYP3A4 and CYP1A2 were the predominant CYP isoforms 
responsible for the metabolism of BN101/belumosudil. 
GLP-compliant rat and dog general toxicology/toxicokinetic studies of acute, subchronic (1 and 
3 month), and chronic (6-month rat and 9-month dog) duration have been completed. The primary 
nonclinical toxicology finding at/near clinically relevant exposures were limited to changes in the 
cardiovascular (BP lowering), hepatic (transaminitis, hypertrophy/increased organ weight, and 
cholestasis/inflammation), renal (increased BUN, tubular changes, pigmentation, intracellular protein 
droplets in the epithelium), GI (decreased appetite), and hematopoietic/immunologic (anemia with 
regeneration and thymic/splenic lymphoid depletion) systems. Safety pharmacology studies [including 
human ether-à-go go related gene (hERG) (in vitro), central nervous system (rat), respiratory system 
(rat), and cardiovascular system (dog)] demonstrated a low likelihood of adverse and/or non-
monitorable central nervous system, respiratory, or cardiovascular system effects associated with 
BN101/belumosudil at clinically relevant exposure levels. Embryo-fetal toxicology (rats and rabbits) 
and fertility (rats) studies showed that BN101/belumosudil demonstrated embryo-fetal 
toxicity/teratogenicity as well as reduced male fertility (reduced fertility index/sperm 
concentration/motility and increased abnormal sperm percentage; testes/epididymis (decreased organ 
weights and degenerative histopathology). Male fertility findings were generally at higher then 
clinically relevant exposures. In addition, there was no evidence of genotoxicity in the in vitro Bacterial 
Reverse Mutation Assay, the in vitro Mammalian Chromosome Aberration Test, or the in vivo 


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Mammalian Erythrocyte Micronucleus Test mutagenicity assay. 
For more information about the BN101/belumosudil nonclinical study see the Investigator's 
Brochure. 
1.4 
Overseas clinical studies of BN101/belumosudil 
The former code for BN101 was KD025, and since the code used for the overseas clinical trial 
was KD025, the use of the former code KD025 has been retained for parts of this protocol. 
To date, 11 clinical studies of BN101/belumosudil have been completed in foreign countries: 
• 
8 Phase 1 studies (SLx-2119-09-01、KD025-101、KD025-102、KD025-103、KD025-
105、KD025-106、KD025-107and KD025-108) designed to determine the safety, 
tolerability, and PK of escalating single- and multiple-oral doses of BN101/belumosudil in 
healthy male and/or post-menopausal female subjects, the potential for drug-drug interactions, 
and Bioavailability and metabolites of BN101/belumosudil. 
• 
3 Phase 2 studies in subjects with psoriasis vulgaris(KD025-205、KD025-206 and KD025-
211). 
In addition, there are 2 phase I studies and 4 ongoing Phase II clinical studies abroad: 
• 
phase 1 PK study of normal liver function and varying degrees of hepatic impairment 
(KD025-109). 
• 
Phase 1 study to investigate the effects of BN101/belumosudil on QTc interval (KD025-110) 
• 
Phase 2 Idiopathic pulmonary fibrosis (KD025-207). 
• 
Phase 2 Diffuse cutaneous systemic sclerosis (KD025-209). 
• 
Phase 2 Chronic graft versus host disease (KD025-208 and KD025-213). 
1.4.1 
Pharmacokinetics 
Final PK data are presented for all eight completed Phase 1 studies in healthy volunteers (Studies 
SLx-2119-09-01、KD025-101、KD025-102、KD025-103、KD025-105、KD025-106、KD025-
107 and KD025-108) and the Phase 2 studies in patients with psoriasis vulgaris (KD025-205、KD025-
206). 
A total of 215 healthy volunteers (210 male and 5 female) were exposed to a single- or multiple-
doses of BN101/belumosudil for a duration up to 28 days, with doses ranging from 20 mg QD to 1000 
mg QD to 500 mg BID. The study drug administered in these studies consisted of capsules or tablets.  
BN101/belumosudil was the main analyte detected in all clinical studies, time to peak plasma 
concentration (Tmax) is 1-6 hours. Cmax and AUC increases slightly greater than dose proportionate 
over the 20 to 500 mg QD range, and less than dose proportionate for doses > 500 mg. After a single 


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oral dose of 200 mg BN101/belumosudil tablets, the absolute bioavailability of BN101/belumosudil 
[AUC based on the AUC from initiation of administration to the imputed infinite time (AUCinf)] is 
64%, it is distributed to the tissues, with an elimination half-life (T1/2) of ~7 hours, and the major routes 
of elimination are the bile and/or the intestine. Little accumulation of BN101/belumosudil has been 
observed after multiple dosing. 
Two metabolites, BN101/belumosudil m1 and BN101/belumosudil m2, rapidly appeared in 
plasma and were readily eliminated. A major metabolite, BN101/belumosudil m2, was detected at Cmax 
levels ~20% that of parent and AUC ~15% that of parent. A minor metabolite, BN101/belumosudil 
m1, was detected at Cmax levels < 5% of parent and AUC ~2% parent. Cmax of and exposure to both 
metabolites increased with dose. Little to no accumulation of BN101/belumosudil m2 or 
BN101/belumosudil m1 was observed after multiple doses of BN101/belumosudil. 
Plasma systemic exposure (Cmax and AUC) of BN101/belumosudil was approximately 2-3–fold 
higher under the fed state compared with the fasted state. As such, it was determined that 
BN101/belumosudil should be taken with food or within 5 minutes of eating. 
The results of the drug interaction study (KD025-107) suggest that CYP3A4 is likely to play a 
major role in the metabolism of BN101/belumosudil to its metabolites BN101/belumosudil m2 and 
BN101/belumosudil m1. While no meaningful effect of itraconazole on the PK of belumosudil was 
noted, a decrease in exposure in both metabolites was observed. Co-administration with rifampicin 
resulted in decreased exposure of belumosudil and BN101/belumosudil m2 (belumosudil Cmax and 
AUC geometric mean ratio [GMR] of 0.28 and 0.45), but an increase in exposure of 
BN101/belumosudil m1 (Cmax and AUC GMR of 2.3 and 2.5, respectively). Geometric mean t½ values 
decreased from 7.89 to 2.17 hours for belumosudil alone and co-administered with rifampicin, 
respectively. 
A delay in absorption was observed when belumosudil was co-administered with a moderate or 
strong PPI. Exposure of both the parent and associated metabolites decreased significantly when 
administered with either PPI (Geometric mean ratios of Cmax and AUC ranged from 0.27 to 0.69 in 
combination with omeprazole [coadministered with omeprazole: BN101/belumosudil monotherapy] 
and from 0.06 to 0.18 in combination with rabeprazole [coadministered with rabeprazole: 
BN101/belumosudil monotherapy]).The above results suggest a continued focus on the use of 
CYP3A4 inducers and proton pump inhibitors and their clinical relevance in clinical studies of 
BN101/belumosudil. 
1.4.2 
Efficacy 
BN101/belumosudil is currently in clinical development in the United States in multiple immune 


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disease areas, as described in Section 1.4, for indications including cGVHD, psoriasis, idiopathic 
pulmonary fibrosis and diffuse cutaneous systemic sclerosis.Clinical trials of BN101/belumosudil for 
the treatment of chronic graft-versus-host disease have been implemented primarily in the United 
States, with a total of two clinical trials (KD025-208 and KD025-213). 
KD025-208 is an Phase 2a, dose-escalation, open-label study to evaluate the safety, tolerability, 
and activity of BN101/belumosudil in subjects with cGVHD who have already received 1-3 prior lines 
of therapy. Of these subjects, 50% had cGVHD involving at least 4 organs and 67% had received ≥2 
lines of prior systemic therapy.Kadmon and the U.S. FDA held a Type B meeting in May 2018, and 
based on the preliminary clinical data from study KD025-208 and the current status of treatment for 
cGVHD, the U.S. FDA agreed to Kadmon's Phase II, open, randomized, multicenter study KD025-
213 as a registrational clinical trial and file an NDA after combining the data from other completed 
clinical studies in aggregate. And subsequently granted Breakthrough Therapy Designation status to 
BN101/belumosudil for cGVHD in October 2018.On July 16, 2021, the U.S. FDA approved the 
marketing of BN101/belumosudil for the treatment of pediatric patients with chronic graft-versus-host 
disease (cGVHD) who have failed prior treatment with at least 2 systemic therapies ( age≥12 years) 
and adult patients. 
BN101/belumosudil in study KD025-208 showed encouraging efficacy, with ORRs of 65%, 69%, 
and 62% as of February 19, 2020 from Cohort 1 (200 mg QD, N = 17), Cohort 2 (200 mg BID, N = 
16), and Cohort 3 (400 mg QD, N = 21), respectively, with complete response (CR) was observed in 
all organs and overall severity (GSR), except in the lungs, where only partial response (PR) was 
observed. Also, efficacy was durable, with a Kaplan-Meier estimated median duration of response 
(DOR) of 35 weeks (8 months) and a median failure-free survival (FFS) of 10.7 months in the mITT 
response subject population. 65% of the subjects had achieved dose reductions in corticosteroid use, 
with 17% of them completely discontinuing systemic corticosteroid therapy while receiving 
BN101/belumosudil. Improvement in Lee Symptom Scale scores was reported in 53%, 44%, and 52% 
of subjects in these 3 cohorts, respectively. 
KD025-213 is a registrational clinical trial with subjects still in follow-up, a Phase II, open, 
randomized, multicenter study designed to evaluate the efficacy and safety of BN101/belumosudil in 
subjects with cGVHD who have undergone at least 2 lines of prior systemic therapy. Subjects were 
randomly assigned to two different BN101/belumosudil dose groups, Group A: BN101/belumosudil 
200 mg QD and Group B: BN101/belumosudil 200 mg BID, with either group meeting the endpoints 
established by the study considered a positive result. The study assumed an expected target ORR of 
55%, with more than 90% certainty that the lower limit of the 95% confidence interval (CI) for the 


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ORR would be greater than 30%, and that approximately 63 patients would be required in each group, 
and that the actual subjects enrolled in the trial would be 66 in each group. As of February 19, 2020 (6 
months after enrollment of the last subject), the ORR in the 200 mg QD group was 72.7% (95% CI: 
60.4, 83.0), CR was 4.5%, and PR was 68.2%; in the 200 mg BID group, the ORR was 74.2% (95% 
CI: 62.0, 84.2), CR was 1.5%, and PR was 72.7%; ORR for all subjects was 73.5% (95% CI: 65.1, 
80.8), CR was 3.0%, and PR was 70.5%. The median duration of response in the 200 mg QD group 
was 21.1 weeks (95% CI: 9.4, NA).The median time to first response in the 200 mg QD group was 4.4 
weeks (95% CI: 3.7, 40.6). Response was observed in all key subgroups. 
1.4.3 
Safety 
As of 19 February 2020, more than 600 individuals have been dosed with BN101/belumosudil as 
participants of Phase 1 and 2 Kadmon sponsored studies, includes healthy volunteers and patients with 
immune or fibrotic diseases taking BN101/belumosudil in doses ranging from 20 to 1000 mg QD and 
500 mg BID. 
Phase I studies completed in 8 healthy volunteers showed that BN101/belumosudil was well 
tolerated and showed an acceptable safety profile across the 20mg-1000mg QD dose range. Very few 
SAEs occurred and none were associated with BN101/belumosudil. One case was an ankle fracture, 
while the two SAEs were caused by moderate hepatic injury from the subjects' underlying disease. 
Elevated liver function tests were reported, but all were mild to moderate and recovered upon 
discontinuation of study drug. Some infectious events, including upper respiratory tract infections, 
were also reported.  
Analysis of Phase 2 safety data from subjects with cGVHD, IPF, and psoriasis suggests an 
acceptable, manageable safety profile for belumosudil. Overall, treatment-emergent AEs (TEAEs) 
have generally been consistent with those expected in the populations enrolled in each of the studies, 
the summarized TEAEs are shown in Table 1. 
Refer to the Investigator's Brochure for details of the BN101/belumosudil clinical PK, 
efficacy and safety summary. 


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Table 1 Treatment Emergent Adverse Events Occurring in ≥5% of Subjects at Any Dose Level in Studies of cGVHD (KD025-208 and KD025-213), IPF 
(KD025-207) or Psoriasis (KD025-205, KD025-206, and KD025-211) by System Organ Class and Preferred Term (Safety Population) 
Note: In view of small sample sizes, data across all doses of belumosudil in psoriasis studies is pooled. 
System Organ Class 
Preferred Term 
Number (%) of Subjects 
cGVHD 
IPF 
Psoriasis 
Total 
N = 186 
200 mg QD 
N = 83 
200 mg BID 
N = 82 
400 mg QD 
N = 21 
400 mg QD 
N = 68 
BSC 
N = 24 
BN101/belumosudil 
N = 148 
Placebo 
N = 18 
Subjects with at least one 
TEAE 
183 (98.4%) 
82 (98.8%) 
81 (98.8%) 
20 (95.2%) 
67 (98.5%) 
18 (75.0%) 
97 (65.5%) 
9 (50.0%) 
Gastrointestinal disorders 
126 (67.7%) 
56 (67.5%) 
54 (65.9%) 
16 (76.2%) 
31 (45.6%) 
5 (20.8%) 
29 (19.6%) 
0 
Diarrhoea 
57 (30.6%) 
27 (32.5%) 
23 (28.0%) 
7 (33.3%) 
17 (25.0%) 
0 
7 (4.7%) 
0 
Nausea 
52 (28.0%) 
23 (27.7%) 
21 (25.6%) 
8 (38.1%) 
7 (10.3%) 
3 (12.5%) 
11 (7.4%) 
0 
Vomiting 
33 (17.7%) 
18 (21.7%) 
11 (13.4%) 
4 (19.0%) 
3 (4.4%) 
0 
8 (5.4%) 
0 
Abdominal pain 
22 (11.8%) 
10 (12.0%) 
8 (9.8%) 
4 (19.0%) 
2 (2.9%) 
0 
0 
0 
Dysphagia 
18 (9.7%) 
12 (14.5%) 
4 (4.9%) 
2 (9.5%) 
1 (1.5%) 
1 (4.2%) 
0 
0 
Constipation 
17 (9.1%) 
8 (9.6%) 
6 (7.3%) 
3 (14.3%) 
4 (5.9%) 
0 
2 (1.4%) 
0 
Dry mouth 
13 (7.0%) 
8 (9.6%) 
5 (6.1%) 
0 
1 (1.5%) 
0 
1 (0.7%) 
0 
Infections and infestations 
116 (62.4%) 
53 (63.9%) 
48 (58.5%) 
15 (71.4%) 
34 (50.0%) 
9 (37.5%) 
37 (25.0%) 
2 (11.1%) 
Upper respiratory tract 
infection 
56 (30.1%) 
24 (28.9%) 
25 (30.5%) 
7 (33.3%) 
7 (10.3%) 
4 (16.7%) 
5 (3.4%) 
1 (5.6%) 
Pneumonia 
17 (9.1%) 
9 (10.8%) 
8 (9.8%) 
0 
7 (10.3%) 
0 
1 (0.7%) 
0 
Influenza 
11 (5.9%) 
3 (3.6%) 
7 (8.5%) 
1 (4.8%) 
3 (4.4%) 
0 
4 (2.7%) 
0 
Respiratory, thoracic and 
mediastinal disorders 
109 (58.6%) 
49 (59.0%) 
46 (56.1%) 
14 (66.7%) 
45 (66.2%) 
13 (54.2%) 
9 (6.1%) 
1 (5.6%) 
Dyspnea 
46 (24.7%) 
22 (26.5%) 
17 (20.7%) 
7 (33.3%) 
19 (27.9%) 
4 (16.7%) 
0 
0 
Cough 
44 (23.7%) 
20 (24.1%) 
17 (20.7%) 
7 (33.3%) 
13 (19.1%) 
8 (33.3%) 
1 (0.7%) 
0 
Productive cough 
19 (10.2%) 
9 (10.8%) 
9 (11.0%) 
1 (4.8%) 
3 (4.4%) 
2 (8.3%) 
0 
0 
Nasal congestion 
18 (9.7%) 
10 (12.0%) 
7 (8.5%) 
1 (4.8%) 
1 (1.5%) 
0 
0 
0 
Hypoxia 
12 (6.5%) 
5 (6.0%) 
3 (3.7%) 
4 (19.0%) 
1 (1.5%) 
0 
0 
0 
General disorders and 
administration site 
conditions 
105 (56.5%) 
49 (59.0%) 
41 (50.0%) 
15 (71.4%) 
24 (35.3%) 
3 (12.5%) 
7 (4.7%) 
0 
Fatigue 
61 (32.8%) 
32 (38.6%) 
20 (24.4%) 
9 (42.9%) 
11 (16.2%) 
1 (4.2%) 
3 (2.0%) 
0 
Oedema peripheral 
41 (22.0%) 
20 (24.1%) 
15 (18.3%) 
6 (28.6%) 
6 (8.8%) 
0 
1 (0.7%) 
0 
Pyrexia 
25 (13.4%) 
14 (16.9%) 
8 (9.8%) 
3 (14.3%) 
1 (1.5%) 
0 
2 (1.4%) 
0 
Musculoskeletal and 
connective tissue disorders 
93 (50.0%) 
42 (50.6%) 
38 (46.3%) 
13 (61.9%) 
24 (35.3%) 
5 (20.8%) 
12 (8.1%) 
0 
Muscle spasms 
30 (16.1%) 
13 (15.7%) 
11 (13.4%) 
6 (28.6%) 
5 (7.4%) 
2 (8.3%) 
0 
0 


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System Organ Class 
Preferred Term 
Number (%) of Subjects 
cGVHD 
IPF 
Psoriasis 
Total 
N = 186 
200 mg QD 
N = 83 
200 mg BID 
N = 82 
400 mg QD 
N = 21 
400 mg QD 
N = 68 
BSC 
N = 24 
BN101/belumosudil 
N = 148 
Placebo 
N = 18 
Arthralgia 
24 (12.9%) 
11 (13.3%) 
8 (9.8%) 
5 (23.8%) 
4 (5.9%) 
0 
4 (2.7%) 
0 
Pain in extremity 
19 (10.2%) 
8 (9.6%) 
7 (8.5%) 
4 (19.0%) 
2 (2.9%) 
0 
0 
0 
Back pain 
13 (7.0%) 
6 (7.2%) 
7 (8.5%) 
0 
7 (10.3%) 
2 (8.3%) 
3 (2.0%) 
0 
Muscular weakness 
12 (6.5%) 
7 (8.4%) 
3 (3.7%) 
2 (9.5%) 
3 (4.4%) 
0 
0 
0 
Myalgia 
11 (5.9%) 
5 (6.0%) 
3 (3.7%) 
3 (14.3%) 
1 (1.5%) 
0 
0 
0 
Investigations 
89 (47.8%) 
39 (47.0%) 
38 (46.3%) 
12 (57.1%) 
26 (38.2%) 
3 (12.5%) 
33 (22.3%) 
3 (16.7%) 
Gamma-glutamyltransferase 
increased 
22 (11.8%) 
9 (10.8%) 
13 (15.9%) 
0 
6 (8.8%) 
1 (4.2%) 
0 
1 (5.6%) 
Alanine aminotransferase 
increased 
21 (11.3%) 
10 (12.0%) 
9 (11.0%) 
2 (9.5%) 
10 (14.7%) 
1 (4.2%) 
11 (7.4%) 
1 (5.6%) 
Aspartate aminotransferase 
increased 
20 (10.8%) 
10 (12.0%) 
9 (11.0%) 
1 (4.8%) 
8 (11.8%) 
0 
7 (4.7%) 
1 (5.6%) 
Blood alkaline phosphatase 
increased 
14 (7.5%) 
8 (9.6%) 
6 (7.3%) 
0 
1 (1.5%) 
0 
0 
0 
Blood creatinine increased 
14 (7.5%) 
4 (4.8%) 
8 (9.8%) 
2 (9.5%) 
3 (4.4%) 
1 (4.2%) 
1 (0.7%) 
0 
Weight decreased 
11 (5.9%) 
5 (6.0%) 
4 (4.9%) 
2 (9.5%) 
2 (2.9%) 
0 
0 
0 
Metabolism and nutrition 
disorders 
77 (41.4%) 
37 (44.6%) 
29 (35.4%) 
11 (52.4%) 
13 (19.1%) 
2 (8.3%) 
8 (5.4%) 
2 (11.1%) 
Hyperglycaemia 
26 (14.0%) 
11 (13.3%) 
12 (14.6%) 
3 (14.3%) 
3 (4.4%) 
0 
1 (0.7%) 
0 
Decreased appetite 
20 (10.8%) 
12 (14.5%) 
4 (4.9%) 
4 (19.0%) 
5 (7.4%) 
0 
0 
0 
Dehydration 
12 (6.5%) 
6 (7.2%) 
4 (4.9%) 
2 (9.5%) 
2 (2.9%) 
0 
1 (0.7%) 
0 
Hyperkalaemia 
12 (6.5%) 
5 (6.0%) 
4 (4.9%) 
3 (14.3%) 
0 
0 
0 
0 
Hypokalaemia 
11 (5.9%) 
6 (7.2%) 
5 (6.1%) 
0 
0 
0 
1 (0.7%) 
0 
Hypophosphataemia 
10 (5.4%) 
5 (6.0%) 
4 (4.9%) 
1 (4.8%) 
0 
0 
0 
0 
Nervous system disorders 
74 (39.8%) 
30 (36.1%) 
35 (42.7%) 
9 (42.9%) 
24 (35.3%) 
4 (16.7%) 
16 (10.8%) 
0 
Headache 
40 (21.5%) 
15 (18.1%) 
19 (23.2%) 
6 (28.6%) 
3 (4.4%) 
1 (4.2%) 
9 (6.1%) 
0 
Dizziness 
12 (6.5%) 
3 (3.6%) 
7 (8.5%) 
2 (9.5%) 
7 (10.3%) 
1 (4.2%) 
3 (2.0%) 
0 
Neuropathy peripheral 
10 (5.4%) 
4 (4.8%) 
5 (6.1%) 
1 (4.8%) 
0 
0 
0 
0 
Skin and subcutaneous 
tissue disorders 
72 (38.7%) 
31 (37.3%) 
33 (40.2%) 
8 (38.1%) 
10 (14.7%) 
3 (12.5%) 
12 (8.1%) 
2 (11.1%) 
Pruritus 
16 (8.6%) 
6 (7.2%) 
10 (12.2%) 
0 
3 (4.4%) 
0 
6 (4.1%) 
1 (5.6%) 
Injury, poisoning and 
procedural complications 
58 (31.2%) 
30 (36.1%) 
22 (26.8%) 
6 (28.6%) 
16 (23.5%) 
3 (12.5%) 
21 (14.2%) 
1 (5.6%) 
Contusion 
18 (9.7%) 
10 (12.0%) 
5 (6.1%) 
3 (14.3%) 
1 (1.5%) 
0 
2 (1.4%) 
0 
Fall 
18 (9.7%) 
8 (9.6%) 
9 (11.0%) 
1 (4.8%) 
4 (5.9%) 
1 (4.2%) 
2 (1.4%) 
0 


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System Organ Class 
Preferred Term 
Number (%) of Subjects 
cGVHD 
IPF 
Psoriasis 
Total 
N = 186 
200 mg QD 
N = 83 
200 mg BID 
N = 82 
400 mg QD 
N = 21 
400 mg QD 
N = 68 
BSC 
N = 24 
BN101/belumosudil 
N = 148 
Placebo 
N = 18 
Vascular disorders 
56 (30.1%) 
25 (30.1%) 
26 (31.7%) 
5 (23.8%) 
7 (10.3%) 
2 (8.3%) 
4 (2.7%) 
0 
Hypertension 
31 (16.7%) 
15 (18.1%) 
12 (14.6%) 
4 (19.0%) 
2 (2.9%) 
0 
3 (2.0%) 
0 
Psychiatric disorders 
34 (18.3%) 
13 (15.7%) 
15 (18.3%) 
6 (28.6%) 
12 (17.6%) 
1 (4.2%) 
9 (6.1%) 
0 
Depression 
12 (6.5%) 
2 (2.4%) 
7 (8.5%) 
3 (14.3%) 
3 (4.4%) 
0 
3 (2.0%) 
0 
Anxiety 
11 (5.9%) 
4 (4.8%) 
5 (6.1%) 
2 (9.5%) 
7 (10.3%) 
0 
1 (0.7%) 
0 
Insomnia 
10 (5.4%) 
6 (7.2%) 
2 (2.4%) 
2 (9.5%) 
5 (7.4%) 
0 
2 (1.4%) 
0 
Renal and urinary 
disorders 
34 (18.3%) 
15 (18.1%) 
15 (18.3%) 
4 (19.0%) 
6 (8.8%) 
1 (4.2%) 
4 (2.7%) 
0 
Acute kidney injury 
11 (5.9%) 
3 (3.6%) 
7 (8.5%) 
1 (4.8%) 
0 
0 
0 
0 
Blood and lymphatic 
system disorders 
30 (16.1%) 
13 (15.7%) 
13 (15.9%) 
4 (19.0%) 
7 (10.3%) 
1 (4.2%) 
1 (0.7%) 
0 
Anaemia 
21 (11.3%) 
10 (12.0%) 
11 (13.4%) 
0 
2 (2.9%) 
1 (4.2%) 
0 
0 
Abbreviations: BID=twice daily; BSC=best supportive care; cGVHD=chronic graft versus host disease; IPF=Idiopathic pulmonary fibrosis; QD=once daily.


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1.5 
BN101-101 Study 
BN101-101 is a randomized, double-blind phase I clinical study conducted in Chinese healthy 
volunteers to evaluate the tolerability, safety and pharmacokinetic (PK) profile of different dose levels 
of BN101/belumosudil administered as a single dose in healthy volunteers. A total of 2 study cohorts 
were enrolled: cohort 1 (BN101/belumosudil or placebo 200 mg single oral dose) and cohort 2 
(BN101/belumosudil or placebo 400 mg single oral dose). A total of 85 subjects were screened for this 
study; 24 subjects were enrolled in the study and underwent randomization, 23 received study drug 
administration, 23 completed the study, and 1 subject withdrew early due to an adverse event prior to 
drug administration. Eleven subjects in cohort 1 received study medication and completed the study, 
of which 8 received BN101 and 3 received placebo; 12 subjects in cohort 2 received study medication 
and completed the study, of which 9 received BN101 and 3 received placebo. 
The 23 subjects included in the modified intention to treat analysis set (mITT) had a mean (range) 
age of 31.7 (20-43) years, 73.9% were male and 26.1% were female, a mean (range) body weight of 
62.76 (49.4-78.5) kg, and a mean (range) BMI of 22.13 (19.5-23.9) kg/m2. 
A total of 4 (17.4%, 4/23) subjects reported 4 TEAEs during the study period; PTs reported by 
subjects receiving BN101 included: decreased body mass index, positive urine leukocytes, and 
elevated blood triglycerides (1 subject each, 5.9%); PTs reported by subjects receiving placebo 
included: abnormal electrocardiogram T waves (1 subject, 16.7%). All TEAEs were grade 1, and no 
subject had a grade 2 or higher TEAE. 
No serious adverse events or deaths were reported during the study period, and no subjects 
withdrew early from the study due to AE. No clinically significant laboratory test abnormalities were 
noted during the study period, with the exception of positive urine leukocytes and elevated blood 
triglycerides (1 subject each receiving BN101, 5.9%). No subject was found to have a QTcF interval 
value of ≥450 ms or a QT interval of ≥480 ms, and no subject had a change in QTcF interval from 
baseline of ≥30 ms after dosing. Overall, BN101 was well tolerated as a single dose at 200 mg and 
400 mg, and no unintended safety events were observed. Overall, BN101 has a favorable safety profile 
in healthy Chinese subjects. 
The PK parameters of plasma BN101 in the subjects are shown in Table 2. BN101 was rapidly 
absorbed after a single oral dose, peaking at a median of 1.5 hours (range: 0.5-2.0 hours); the 
elimination half-life was highly variable, with a median elimination half-life of 10.35 hours and 8.92 
hours at the 200 mg dose and 400 mg dose, respectively. Overall, the AUC0-24 of BN101 increased 
slightly with dose, but was lower than dose proportionality, with a mean AUC0-24 of 9040.44 ng*h/mL 
at the 200 mg dose and 9984.00 ng*h/mL at the 400 mg dose, respectively.The Cmax was similar in the 


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2 dose cohorts, with a mean Cmax of 2355.02 ng*h/mL at the 200 mg dose and 2355.02 ng*h/mL at the 
400 mg dose, respectively. 
 
Table 2 Plasma BN101/belumosudil pharmacokinetic parameters-PK analysis set 
Treatment 
group 
Statistic 
PK Parameters 
AUC0-24 
(ng*h/mL) 
AUC0-∞ 
(ng*h/mL) 
Cmax 
(ng/mL) 
T1/2 
(h) 
Tmax 
(h) 
BN101 
200mg 
(N=8) 
Median 
6883.41 
7635.11 
2204.59 
10.35 
1.50 
Minimum 
4057.36 
4490.96 
976.96 
2.13 
0.5 
Maximum 
18074.16 
19561.24 
4265.25 
48.01 
2.0 
Arithmetic 
mean 
9040.44 
10055.32 
2355.02 
14.28 
/ 
Coefficient 
of variation 
58.64 
59.39 
45.53 
103.52 
/ 
BN101 
400mg 
(N=9) 
Median 
8120.87 
10264.37 
2181.44 
8.92 
1.50 
Minimum 
4426.67 
4837.27 
941.48 
3.85 
0.5 
Maximum 
19691.89 
20375.86 
3939.14 
28.69 
2.0 
Arithmetic 
mean 
9984.00 
10981.49 
2315.84 
11.80 
/ 
Coefficient 
of variation 
56.21 
51.12 
48.25 
69.22 
/ 
N is the number of subjects entering the analysis set in each group. 
1.6 
Rationale for the design of this study 
As BN101/belumosudil has completed clinical development for cGVHD in the U.S., the 
registration study (KD025-213) met clinical endpoints and supported the conclusion that benefits 
outweighed risks. A rolling submission NDA for the cGVHD indication based on this study was 
also completed at the end of November 2020 and was fully approved by the FDA on July 16, 2021 
in the United States. Given the global development status of BN101/belumosudil in the cGVHD 
indication, and based on the recommendation of the NMPA, we first conducted a PK bridging 
clinical trial in healthy volunteers to initially assess the safety, drug exposure and metabolites of 
BN101/belumosudil in healthy individuals to determine the BN101/ belumosudil starting dose and 
PK profile. Given that the PK bridging clinical trial in healthy volunteers has been substantially 
completed and met the bridging objective, the Sponsor currently plans to conduct a bridging study 
to evaluate the efficacy, safety and PK characteristics of BN101/belumosudil for the treatment of 
Chinese patients with cGVHD. This bridging study is an open, single-arm trial in Chinese patients 
with cGVHD, and because it is designed for bridging purposes, the sample size is not determined 
by statistical assumptions. 
This study is planned to enroll 30 patients with cGVHD who have undergone at least 1 but 
not more than 5 lines of systemic therapy. Considering that the recommended dose of both cGVHD 
clinical trials in Western populations was 200 mg QD and the highest administered dose of 
BN101/belumosudil in the phase I dose-escalation study reached 1000 mg QD/500 mg BID and 


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was well tolerated, combined with the pharmacokinetic profile of 200 mg orally in the phase I 
study in Chinese healthy volunteers was consistent with the results in the overseas study, without 
any TEAE associated with the investigational drug, the starting dose of this cGVHD bridging 
clinical trial was also set at 200 mg QD. 
2. STUDY OBJECTIVES/PRUPOSE 
Primary Objective： 
 
To evaluate the efficacy and safety of BN101/belumosudil in subjects with cGVHD who had 
previously been treated with at least 1 prior line of systemic therapy. 
Secondary Objectives 
 
To evaluate the PK profile of BN101/belumosudil in subjects with cGVHD who had previously 
been treated with at least 1 prior line of systemic therapy;  
 
To evaluate other efficacy endpoints of BN101/belumosudil in subjects with cGVHD who had 
previously been treated with at least 1 prior line of systemic therapy. 
Exploratory Objective 
 
To evaluate changes in the Patient-Reported Outcomes (PRO) Measurement Information System 
(PROMIS) Global Health sub-scores of physical and mental functioning. 
3. STUDY POPULATION 
3.1 
Inclusion Criteria 
Subjects who met all of the following conditions could be enrolled in the study: 
(1) Male or female subjects aged ≥ 18 years who have had allogeneic hematopoietic stem cell 
transplant (allo-HSCT). 
(2) Have persistent cGVHD manifestations and systemic therapy is indicated. 
(3) Previously received at least 1 and not more than 5 lines of systemic therapy for cGVHD2. 
(4) Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening; or 4 weeks 
of prednisone or equivalent doses of other corticosteroids at doses > 0.5 mg/kg/day with persistent 
manifestations of cGVHD and no improvement; or 2 attempts to reduce the hormone to a lower 
 
 
2 The following approach should be used when documenting prior cGVHD treatment： 
• 
The initiation of one or more new systemic therapies for cGVHD will be considered the initiation of a new 
first-line treatment 
− 
If multiple medications are intended to be initiated at the same time, the dates of initiation of treatment 
with different medications may be spaced up to 4 weeks apart due to schedule delays or medication 
availability 
• 
Topical medications are not considered a line of therapy 


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dose level fail and the prednisone dose still needs to be increased to > 0.25 mg/kg/day or an 
equivalent dose. 
(5) Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0 to 1. 
(6) Life expectancy of more than 12 months. 
General Criteria 
(7) Female subjects of childbearing potential have a negative serum pregnancy test at screening. 
Females of childbearing potential are defined as sexually mature females without prior 
hysterectomy or who have had any evidence of menses in the past 12 months. However, females 
who have been amenorrheic for 12 or more months are still considered to be of childbearing 
potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian 
suppression. 
(8) Sexually active females 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： 
• 
Intra-uterine contraceptive device plus 1 barrier method； 
• 
Stable doses of hormonal contraception (e.g., oral, injectable, subcutaneously implanted, 
transdermal) for at least 3 months plus 1 barrier method； 
• 
Two 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. 
(9) For male subjects who are sexually active and who are partners of females of childbearing potential: 
must agree to use 2 recognized methods of contraception during the treatment period and for 3 
months after the last dose of study drug (see criterion 8 above). 
(10) Subject (or the subject's legally authorized representative) must be fully informed of the study 
contents and is able to provide written ICF prior to any study-specific procedures, and is willing to 
follow the treatment regimen and visit schedule. 
3.2 
Exclusion Criteria 
Subjects who met any of the following conditions would be excluded from the study： 
(1) Received a systemic investigational cGVHD treatment within 28 days of study entry, but prior 
treatment is allowed with a washout of at least 28 days or 5 half-lives.[Note: Corticosteroids, 
CNIs, sirolimus, mycophenolate mofetil (MMF), methotrexate, azathioprine, and in vitro 
photochemotherapy (ECP) are acceptable and subjects must have been on a stable 
dose/regimen of these for at least 2 weeks prior to screening]. 


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(2) Recurrence of hematologic tumor (according to criteria for recurrence of the corresponding 
primary hematologic tumor) or post-transplant lymphoproliferative disease at screening. 
(3) Current treatment with ibrutinib (except for ibrutinib with a washout of at least 28 days prior to 
the first dose of the investigational product). 
Laboratory Tests 
(4) Absolute neutrophil count (ANC) < 1.5 × 109/L. 
(5) Platelet count < 50 × 109/L. 
(6) Alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN), aspartate 
aminotransferase (AST) > 3 × ULN 
(7) Total bilirubin (TBIL) > 1.5 × ULN. 
(8) Creatinine clearance (CrCl) < 60 mL/min (Cockcroft-Gault formula). 
General Criteria 
(9) Pregnant or lactating women. 
(10) 
History of severe illness, or other evidence of severe illness, or any other conditions that 
would make the subject, in the opinion of the investigator, unsuitable for the study 
• 
History of severe [New York Heart Association (NYHA) functional class III or IV] 
cardiovascular disorder, including but not limited to ventricular arrhythmias requiring clinical 
intervention, uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or 
diastolic blood pressure ≥ 100 mmHg); unstable angina pectoris, acute coronary syndrome, 
congestive cardiac failure, stroke, or other ≥ Grade 3 cardiac events within 6 months prior to 
enrollment; and NYHA functional class ≥ II or left ventricular ejection fraction (LVEF) < 50% 
by cardiac ultrasound at screening. 
• 
Inability to take oral medications, severe (NCI CTCAE v5.0≥ Grade 3) chronic 
gastrointestinal dysfunction, malabsorption syndrome, or any other condition that affects 
gastrointestinal absorption. 
• 
History of clear neurological or mental disorders (including epilepsy or dementia), current 
mental disorders, or poor compliance that rendered the subject ineligible for participation in 
the study as judged by the investigator. 
• 
History of other serious (NCI CTCAE v5.0≥ Grade 3) systemic disease that rendered the 
subject ineligible for participation in the clinical trial as judged by the investigator. 
(11) 
Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or human 
immunodeficiency virus (HIV) infection. [Note: Active HBV infection is defined as positive 
for serum hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus e antigen 
(HBeAg), or HBV-DNA; subjects with positive hepatitis B virus core antibody (anti-HBc) 


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should be confirmed for HBV-DNA, and subjects who are confirmed to be negative for HBV-
DNA could be enrolled; active HCV infection is defined as positive for HCV-RNA, and 
subjects who are positive for hepatitis C virus antibody (HCV-Ab) could only be enrolled after 
confirmed to be negative for HCV-RNA. Positive is defined as ＞ the ULN]. 
(12) 
Diagnosed with another primary malignancy(other than malignancy for which allo-HSCT 
was performed) within 3 years of enrollment, with the exception of: 
• 
Completely resected basal cell or squamous cell carcinoma of the skin; 
• 
Surgically cured carcinoma in situ of the cervix; 
• 
Resected breast ductal carcinoma in situ; 
• 
Prostate cancer with Gleason score < 6 and stable prostate-specific antigen (PSA) over 12 
months. 
(13) 
Known allergy to the active ingredient or excipients of the investigational product, or any 
other selective ROCK2 inhibitors. 
(14) 
Subjects requiring long-term proton pump inhibitors (e.g., rabeprazole, omeprazole) or 
CYP3A4 inducers (e.g., rifampin, phenobarbital). 
(15) 
Prolongation of QT interval corrected by the Fridericia's formula (QTcF) of > 450 ms for 
males and > 470 ms for females at screening. 
(16) 
Known alcohol or drug dependence. 
(17) 
Forced expiratory volume in 1 second (FEV1) ≤ 39% or pulmonary function score of 3 at 
screening. 
(18) 
Treatment with any investigational agent, device, or procedure, within 28 days (or 5 half-
lives, whichever is longer) prior to enrollment. 
(19) Subjects considered unlikely to adhere to treatment and follow protocol in the opinion of the 
investigator. 
3.3 
Criteria for completion of study drug therapy and early termination of study drug therapy 
Eligible subjects will be enrolled to receive BN101/belumosudil (every 28-day cycle) until 
cGVHD progression【Evaluated by the investigator based on the National Institutes of Health (NIH) 
Consensus Development Project on Criteria for Clinical Trials in cGVHD(2014) diagnosis and staging, 
and response criteria, hereinafter referred to as the NIH Consensus Criteria (2014)】, intolerable 
toxicity, initiation of a new cGVHD therapy, recurrence of hematological neoplasm (according to the 
recurrence criteria of the corresponding primary hematologic tumor), loss to follow-up, withdrawal of 
consent, or death, etc., whichever occurred first. 
For subjects assessed as "Lack of Response - Mixed" and "Lack of Response - Progression" (See 


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section 7.1.1, table 4) , if the investigator believed that these subjects could continue to benefit from 
treatment with BN101/belumosudil, the treatment may be continued after a written application was 
submitted, and approval from the Sponsor's Medical Director as well as documentation of the subject's 
willingness to continue treatment was obtained. In such cases, the rationale for continuing treatment 
must be clearly documented. In addition, "Lack of Response - Mixed" will be considered a progression 
event in the analysis of outcomes. 
For subjects who did not achieve any response after 12 cycles of BN101/belumosudil treatment 
during the main study(the end of the main study is defined in section 3.5 of the main body), they should 
discontinue the investigational product treatment and withdraw from the study if they were judged by 
the investigator to have no clinical benefit (e.g., improvements in organ score, improvements in Lee 
symptom scores, reductions of corticosteroid/tacrolimus doses). 
(1) Completion of study drug therapy 
• 
Completion of study drug therapy as defined by the protocol;  
• 
cGVHD disease progression during treatment;  
• 
Death of the subject. 
(2) Early termination of study drug therapy 
Refers to the situation in which an enrolled subject becomes unfit to continue treatment with the 
study drug during the course of the study. Early termination of study drug treatment is defined as 
follows: 
• 
Recurrence of the subject's hematologic tumor during the course of the trial (according to the 
criteria for recurrence of the corresponding primary hematologic tumor). 
• 
The subject is discontinued due to an adverse event or serious adverse event that makes 
continuation of study drug treatment inappropriate; or the subject is discontinued due to an adverse 
event or serious adverse event for more than 14 days. 
• 
The investigator determines that the subject's continued treatment with the study drug may pose a 
potential risk greater than benefit to the subject, including: pregnancy; enrollment in the study and 
discovery that the subject does not meet the study protocol inclusion  criteria and that continued 
treatment with the study drug poses a risk greater than benefit to the subject; failure to follow the 
protocol or doctor's orders, unauthorized use of other treatments, or failure to take the medication 
in a timely manner and at a dosage that would interfere with the assessment of efficacy and 
increase potential safety risks. 
• 
Subject withdraws informed consent/withdraws from the study. 
• 
Subject lost to follow-up. 
After discontinuation of study medication, subjects will undergo end-of-treatment visits and enter 


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a safety follow-up period (including a 28-day follow-up after the last dose and a long-term safety 
follow-up). 
Subjects have the right to withdraw from the study at any stage of the study under the terms of 
informed consent, or to be "withdrawn" (or "dropped") from the study even if they do not explicitly 
withdraw from the study but no longer accept the study medication or the study evaluations. The 
reasons for withdrawal should be understood and documented to the extent possible, e.g., perceived 
intolerance of certain AEs associated with the study drug, other reasons for not being able to continue 
in the clinical study, or unexplained loss of visits. 
(3) Treatment of withdrawn subjects 
The investigator must complete the reason for the subject's withdrawal from the study on the 
electronic case report form (eCRF) and contact the subject to complete the evaluation program for the 
end-of-treatment visit (EOT) and safety follow-up (28 ± 7 days after the last dose of study drug or 
prior to initiation of a new treatment for systemic cGVHD) whenever possible, and keep records, 
documenting, whenever possible, the time of the subject's last dose of study drug. The eCRF should 
be retained for subjects who withdraw from the trial for whatever reason. 
During the main study, after a subject terminates study treatment, the investigator must follow up 
on all pre-existing AEs and SAEs that occurred during the Safety Follow-Up Period [28 ± 7 days after 
the last dose of study drug or prior to initiation of new treatment for systemic cGVHD, whichever 
occurs first], report on new AEs and SAEs (whether or not related to the study drug) occurring during 
this period, with SAEs and AEs related to the study drug to be followed up until resolution of the AE 
and SAE, and until, in the investigator's opinion, the event is stabilized or irreversible. Any SAE is 
required to follow the SAE Reporting Procedures (see Section 8.6.2.2) and contact the sponsor in a 
timely manner. 
3.4 
Early Termination of the Study/Closure of the Research Center 
The Sponsor has the right to terminate the Study at any time and the Sponsor and the Investigator 
have the right to close the Research Center at any time. This, of course, can only be carried out after 
mutual agreement. Termination of the study must be reported to the Institutional Review Board (IRB) 
and the Ethics Committee (EC). Upon early termination of the study or early closure of the research 
center, all study materials (except for documents that must be retained at the research center) must be 
returned to the sponsor. The investigator must retain other documents until notified of their destruction 
by the sponsor. Reasons for early termination of a trial or closure of a research center include, but are 
not limited to, the following reasons: 
• 
New information leads to unfavorable risk/benefit judgments about the study drug, e.g., due to: 


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– lack of efficacy of the study drug, either in this or other studies; or 
– other unfavorable safety findings, including clinical examination and non-clinical 
manifestations; 
• 
In the opinion of the sponsor, continuation of the study is not justified for medical, ethical, or   
commercial reasons; 
• 
It is unlikely that the study will be completed within an acceptable timeframe due to difficulties 
in enrolling subjects; 
• 
Suspension or termination due to requirements of health/regulatory authorities. 
3.5 
End of study 
Data lock and primary analysis will be performed 6 months after enrollment of the last subject. 
All subjects will continue to be followed up for an additional 6 months after the primary analysis as 
required by the protocol, i.e., the study will end 12 months after enrollment of the last subject, and a 
follow-up analysis will be performed at the end of the study. Subjects who have not yet experienced 
cGVHD progression at the end of the study, and in the judgment of the investigator, the benefits of 
continued dosing outweigh the risks, may submit a written request and, upon approval by the sponsor's 
Medical Director and documentation of the subject's willingness to continue the treatment, the sponsor 
will continue to provide BN101/belumosudil medication at no cost until cGVHD progression, 
intolerable toxicity, initiation of a new cGVHD therapy, recurrence of hematological neoplasm, loss to 
follow-up, withdrawal of consent, or death, etc., whichever occurred first. If, in the judgment of the 
investigator, there is no evidence of clinical benefit, withdrawal from the study is required. Subjects 
who remain free of disease progression at the time of withdrawal from the study or who withdraw from 
the study for reasons other than adverse events should have the dose of BN101/belumosudil tapered 
every 2 weeks as required by the protocol (e.g., 200 mg QD  200 mg QOD  discontinue treatment). 
Serious adverse events (SAEs), study drug use, and subject survival will continue to be collected 
for subjects who continue to be free of charge while the study drug, BN101/belumosudil, is 
administered at the end of the study. 
The study will end when all subjects stop taking the study drug (Unless terminated earlier for the 
reasons set forth in Section 3.4). 
4. STUDY DESIGN 
4.1 
Type of study and design rationale 
Trial Design： 
This study is a multicenter, open, single-arm phase II clinical trial to enroll 30 patients with 


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cGVHD who have undergone at least 1 but not more than 5 lines of systemic therapy, to evaluate the 
efficacy, safety, and PK characteristics of BN101/belumosudil in Chinese patients with cGVHD. 
Subjects who sign an EC-approved ICF with confirmed screening eligibility will be enrolled to 
receive BN101/belumosudil (every 28-day cycle). Concomitant use of other cGVHD treatments (e.g., 
corticosteroids, CNI, MMF, sirolimus, and ECP) that had been stabilized in dose/regimen prior to 
screening was permitted during the study period, but initiation of new systemic cGVHD treatments 
was not permitted. Efficacy assessments were performed on Day 1 of Cycles 2 to 5 and every 2 cycles 
thereafter (i.e., Day 1 of Cycles 2, 3, 4, 5, 7, 9, 11, etc.). For subjects assessed as "Lack of Response - 
Mixed" and "Lack of Response - Progression" (See section 7.1.1, table 4) , if the investigator believed 
that these subjects could continue to benefit from treatment with BN101/belumosudil, the treatment 
may be continued after a written application was submitted, and approval from the Sponsor's Medical 
Director as well as documentation of the subject's willingness to continue treatment was obtained. For 
subjects who did not achieve any response after 12 cycles of BN101/belumosudil treatment during the 
main study(the end of the main study is defined in section 3.5 of the main body), they should 
discontinue the investigational product treatment and withdraw from the study if they were judged by 
the investigator to have no clinical benefit (e.g., improvements in organ score, improvements in Lee 
symptom scores, reductions of corticosteroid/tacrolimus doses). Subjects who remain free of disease 
progression at the time of withdrawal from the study or who withdraw from the study for reasons other 
than adverse events should have the dose of BN101/belumosudil tapered every 2 weeks as required by 
the protocol (e.g., 200 mg QD  200 mg QOD  discontinue treatment). 
Data lock and primary analysis will be performed 6 months after enrollment of the last subject. 
All subjects will continue to be followed up for an additional 6 months after the primary analysis as 
required by the protocol, i.e., the study will end 12 months after enrollment of the last subject, and a 
follow-up analysis will be performed at the end of the study. Subjects who have not yet experienced 
cGVHD progression at the end of the study, and in the judgment of the investigator, the benefits of 
continued dosing outweigh the risks, the sponsor will continue to provide BN101/belumosudil 
medication at no cost until cGVHD progression, intolerable toxicity, initiation of a new cGVHD 
therapy, recurrence of hematological neoplasm, loss to follow-up, withdrawal of consent, or death, etc., 
whichever occurred first. 
Serious adverse events (SAEs), study drug use, and subject survival will continue to be collected 
for subjects who continue to be free of charge while the study drug, BN101/belumosudil, is 
administered at the end of the study. 
Subjects who have not terminated BN101/belumosudil treatment at the end of the main study will 


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have a uniform end-of-treatment visit at the end of the main study. 
AEs that remain at the end-of-treatment visit will be subject to continued follow-up, and all SAEs 
and AEs related to study treatment will be subject to follow-up until the event is resolved and the 
investigator considers the event to be stabilized or irreversible. 
Twelve subjects at the designated centers will receive dense PK blood collection and the 
remaining subjects will receive sparse PK blood collection. 
The primary efficacy endpoint of the study was ORR, defined as the proportion of subjects 
evaluated as CR or PR according to the NIH Consensus Criteria (2014) at any one post-baseline 
assessment. Secondary efficacy endpoints included median Duration of Response (DOR), Change in 
Lee Symptom Scale Score, Response rate by organ system, Percentage of subjects with best efficacy 
as PR and percentage of subjects with best efficacy as CR, Change in corticosteroid dose, Change in 
CNI dose, Failure-Free Survival (FFS), Overall Survival (OS), Change in cGVHD severity based on 
the Physician-Reported Global cGVHD Activity Assessment, and Change in symptom activity based 
on cGVHD Activity Assessment Patient Self-Report. 
Changes in the PROMIS Physical Psychological Functioning Global Health Score will be 
analyzed as an exploratory endpoint of this study. 
If a subject withdraws early from the study, the withdrawn subject will not need to be replaced 
and will not be able to re-enter this trial. 
4.2 
Randomization and blinding 
This study is a non-randomized, open-label design that does not require randomization or blinding, 
and will use subject numbers to differentiate between subjects. 
Patients who have signed the ICF will be assigned a subject number for screening evaluation in 
the format of "XX-XXX", where the first two digits of "XX" are the study center number and the last 
three digits of "XXX" are the subject number in the format of "XX-1XX" for the first screening and 
"XX-2XX" for the second screening. If the subject number of the first screening for the first subject in 
Center 01 is 01-101, the subject number of the third screening for the first time in Center 02 is 02-103, 
and if the subject needs to undergo the second screening, the subject number of the second screening 
is 02-203, and so on. 
Subject numbers will be assigned in strict order in this trial, and in the event of a subject who 
withdraws early from the study, that subject's number will no longer be used. 
4.3 
Experimental Procedures and Phases 
The study procedures are described in Appendix 1. In addition to the assessment items described 
in this protocol, with the consent of the subject, the investigator may take a series of photographs to 


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further document changes in cGVHD (e.g., skin, joint range of motion). 
4.3.1 
Screening/baseline period (-14 days ~ -1 day) 
The screening period begins with the signing of the ICF. The ICF must be signed before any 
study-required or study-related operation, procedure, or assessment is performed. Patients must be 
given sufficient time to ask questions and make voluntary decisions before signing the ICF. 
Data on screening failures also need to be recorded in the electronic data capture (EDC) system. 
Unless otherwise specified, the Screening Period Assessment Program was to be completed 
within 14 days prior to the first administration of study drug. Subjects who meet all inclusion criteria 
while not meeting any of the exclusion criteria may be enrolled in the study. Subjects' eligibility for 
enrollment must be confirmed by the sponsor's Medical Director or Contract Research Organization 
(CRO) medical monitor prior to administration of study drug. Subjects who fail screening are permitted 
to be rescreened 1 time with the approval of the Medical Monitor; however, candidate subjects who 
fail screening because of abnormal laboratory indicators may not be rescreened after medical 
intervention. Subjects undergoing rescreening must sign a new ICF and be given a new screening 
number, and are permitted to receive the test(s) for which they passed the previous screening if they 
passed the previous screening test and are within the time window for this screening. 
The procedures and assessments for the specific screening period are as follows: 
1) Obtain written informed consent; 
2) Demographic information (including gender, age/date of birth, ethnicity); 
3) Past medical history; 
4) History of transplantation (including indications for transplantation and type of transplantation); 
5) History of GVHD (acute and chronic); 
6) History of cGVHD treatment (including previous lines of therapy for cGVHD); 
7) cGVHD severity assessment (-7 days to -1 day); 
8) Full physical examination (including height); 
9) Vital signs (including temperature, respiratory rate, sitting blood pressure and pulse); 
10) weight and body mass index (calculated from height and weight: BMI = weight (kg)/height2 (m2)); 
11) ECOG PS score; 
12) blood routine, urinalysis, blood biochemistry (-7 days to -1 day); 
13) Virology; 
14) 12-lead ECG (supine position); 
15) Echocardiogram [left ventricular ejection fraction (LVEF)]; 
16) Serum pregnancy test (-7 days to -1 day, for women of childbearing age only); 


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17) Co-administered medications/treatments (including doses of corticosteroids and other cGVHD 
treatments); 
18) Pre-treatment events (PTE); 
19) Physician cGVHD activity assessment (-7 days to -1 day); 
20) Complete pulmonary function tests [-7 days to -1 day, including FEV1, FVC, carbon monoxide 
diffusion (DLCO, corrected for Hb), total lung capacity (TLC), and residual air volume (RV)]; 
21) Patient-reported cGVHD activity assessment (-7 days to -1 day); 
22) Lee Symptom Scale score (-7 days to -1 day); 
23) PROMIS Physical Psychological Functioning Global Health Score (-7 days to -1 day); 
24) Review of inclusion/exclusion criteria. 
4.3.2 
Cycle 1 
4.3.2.1 Cycle 1, Day 1 (C1D1) 
Prior to dosing 
1) Co-administered medications/treatments (including doses of corticosteroids and other cGVHD 
treatments); 
2) PTE； 
3) Symptom-directed physical examination; 
4) Vital signs (including temperature, respiratory rate, sitting blood pressure and pulse); 
5) body weight; 
6) ECOG PS score; 
7) Blood routine、urinalysis、blood biochemistry； 
8) 12-lead electrocardiogram [3 consecutive measurements within 60 minutes prior to drug 
administration, each 1-2 minutes apart]; 
9) chocardiogram (LVEF) #; 
10) Urine pregnancy test (for women of childbearing age only, positive results to be confirmed by 
serologic testing)§； 
11) PK blood collection (within 60 minutes prior to dosing, only for subjects receiving intensive PK 
blood collection); 
 If a subject has had these tests performed within 3 days prior to the administration of this study drug, the above tests 
do not need to be performed again on the day of study drug administration. 
# It is up to the investigator to decide whether or not to perform this test based on the subject's condition. 
§ If a subject has had a serum pregnancy test within 7 days prior to the administration of this study drug, the test does 
not have to be repeated on the day of study drug administration. 


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Drug administration and post administration 
1) Administration of study drug; 
2) Issue study drug and subject logs; 
3) 12-lead electrocardiogram [1.5 hours (±20 minutes) after drug administration, with 3 consecutive 
measurements taken at 1- to 2-minute intervals]; 
4) PK blood collection [only for subjects undergoing intensive PK blood collection: 1 hour (± 10 
minutes), 1.5 hours (± 10 minutes), 2 hours (± 10 minutes), 3 hours (± 10 minutes), 4 hours (± 15 
minutes), 6 hours (± 15 minutes), 8 hours (± 15 minutes), 12 hours (± 60 minutes), and 24 hours 
(± 60 minutes, which was before administration on Day 2)]; 
5) Combined medications/treatments (including doses of corticosteroids and other cGVHD 
treatments); 
6) AE. 
4.3.2.2 Cycle 1, days 8 and 15 (C1D8, C1D15, time window for targeting the appropriate 
examination: ±3 days) 
1) Symptom-directed physical examination; 
2) Vital signs (including temperature, respiratory rate, sitting blood pressure and pulse); 
3) Body weight; 
4) Blood routine and blood biochemistry; 
5) Echocardiogram (LVEF)#; 
6) PK blood collection (within 60 minutes prior to drug administration, day 15 only); 
7) Study drug administration; 
8) Issuance/retrieval of subject logs; 
9) Combined medications/treatments (including doses of corticosteroids and other cGVHD 
treatments); 
10) AE. 
# It is up to the investigator to decide whether or not to perform this test based on the subject's condition. 
4.3.3 
Day 1 of Cycle 2 ~ Cycle N (C2D1 ~ CxD1, time window for the corresponding 
examination: ±3 days): 
Prior to dosing 
1) Co-medication/treatment (including doses of corticosteroids and other cGVHD treatments); 
2) AE 
3) Symptom-directed physical examination; 
4) Vital signs (including temperature, respiratory rate, sitting blood pressure and pulse); 


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5) Body weight; 
6) ECOG PS score; 
7) Blood routine, urine, and blood biochemistry; 
8) 12-lead electrocardiogram (3 consecutive measurements taken within 60 minutes prior to dosing 
on Day 1 of Cycle 2 and Cycle 4, each 1 to 2 minutes apart); 
9) Echocardiogram (LVEF)#; 
10) Urine pregnancy test (for females of childbearing age only, positive results to be confirmed by 
serologic testing); 
11) PK blood collection (within 60 minutes prior to dosing on Cycle 2, Cycle 3 and Cycle 4 Day 1); 
12) Physician cGVHD activity assessment†; 
13) cGVHD response assessment†; 
14) Pulmonary function tests† [may also be assessed post-dose; where a complete pulmonary function 
test including FEV1, FVC, DLCO (corrected for Hb), TLC, and RV is required on Day 1 of Cycle 
4, Cycle 7, and every 6 cycles thereafter (e.g., Cycle 13, Cycle 19, as applicable), and on other 
cycles (e.g., Cycle 2, Cycle 3, Cycle 5, and Cycle 6, etc.), a spirometer test only (including FEV1 
and FVC testing) is required]; 
15) Patient-reported cGVHD activity assessment†; 
16) Lee Symptom Scale score†; 
17) PROMIS Physical-Psychological Functioning Global Health Score†. 
# The decision to perform this test was made by the investigator on a subject-by-subject basis. 
† ssessments were performed on day 1 of cycles 2 to 5 and on day 1 of every 2 cycles thereafter (i.e., day 1 of cycles 
2, 3, 4, 5, 7, 9, 11, etc.). 
Drug administration and post administration 
1) Administration of study drug; 
2) Dispensing/recovery of study drug and subject logs; 
3) Combined medications/treatments (including doses of corticosteroids and other cGVHD 
treatments); 
4) AE; 
5) 12-lead electrocardiogram [3 consecutive measurements 1.5 hours (± 20 minutes) after dosing on 
Day 1 of Cycle 2 and Cycle 4 at 1-2 minute intervals; single measurement 1.5 hours (± 20 minutes) 
after dosing on Cycle 7 and subsequent visits]; 
6) PK blood collection [For subjects receiving intensive PK blood collection: 1 hour (± 10 minutes), 
1.5 hours (± 10 minutes), 2 hours (± 10 minutes), 3 hours (± 10 minutes), 4 hours (± 15 minutes), 
6 hours (± 15 minutes), 8 hours (± 15 minutes), 12 hours (± 60 minutes), 24 hours (± 60 minutes, 


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i.e., before Day 2 administration), 1.5 hours (± 10 minutes), and 4 hours (± 10 minutes) after Day 
1 administration in Cycle 4; for subjects undergoing sparse PK blood collection: 1.5 hours (± 10 
minutes), and 4 hours (± 10 minutes) after Day 1 administration in Cycle 2 and Cycle 4]. 
4.3.4 
End-of-treatment visit (within 7 days after the last dose or at the end of the main 
study) 
If a subject terminates study drug treatment for any reason (other than loss of visit, death), an 
end-of-treatment visit needs to be completed within 7 days of the last dose of study drug. If the subject 
voluntarily requests to withdraw from the study, every effort should also be made to convince the 
subject to accept the end-of-treatment visit. If the subject has not terminated study drug treatment at 
the end of the main study, an end-of-treatment visit is also required at the end of the main study. This 
visit is assessed as follows: 
1) Combined medications/treatments (including doses of corticosteroids and other cGVHD 
treatments); 
2) AE; 
3) Symptom-directed physical examination; 
4) Vital signs (including temperature, respiratory rate, sitting blood pressure and pulse); 
5) Body weight; 
6) ECOG PS score; 
7) Blood routine, urine, and blood biochemistry; 
8) 12-lead electrocardiogram; 
9) Echocardiogram (LVEF)#； 
10) Urine pregnancy test (for females of childbearing age only, positive results to be confirmed by 
serologic testing); 
11) Recovery of study drug and subject logs; 
12) Physician cGVHD activity assessment; 
13) cGVHD response assessment; 
14) Complete Pulmonary Function Test [If a complete pulmonary function test was performed within 
one month prior to this visit, only spirometry (including FEV1 and FVC) is required this time]; 
15) Patient-reported cGVHD activity assessment; 
16) Lee Symptom Scale score； 
17) PROMIS Physical-Psychological Functioning Global Health Score. 
# The decision to perform this test was made by the investigator on a subject-by-subject basis. 
4.3.5 
Follow-up 28 days after last dose (±7 days) 


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1) Combined medications/treatments (including doses of corticosteroids and other cGVHD 
treatments); 
2) AE; 
3) Symptom-directed physical examination; 
4) Vital signs (including temperature, respiratory rate, sitting blood pressure and pulse); 
5) Body weight; 
6) ECOG PS score; 
7) Blood routine, urine, and blood biochemistry; 
8) 12-lead electrocardiogram; 
9) Echocardiogram (LVEF)#； 
10) Urine pregnancy test (for females of childbearing age only, positive results to be confirmed by 
serologic testing). 
# The decision to perform this test was made by the investigator on a subject-by-subject basis. 
4.3.6 
Long-Term Safety Follow-Up 
Subjects who terminate study treatment early before the end of the main study will be contacted 
by telephone by the study center approximately every 12 weeks to confirm their survival, any changes 
in cGVHD treatment, and any antitumor therapy until the end of the main study (see Section 3.5). 
Subjects who have not yet experienced cGVHD progression at the end of the study, and in the 
judgment of the investigator, the benefits of continued dosing outweigh the risks, may submit a written 
request and, upon approval by the sponsor's Medical Director and documentation of the subject's 
willingness to continue the treatment, the sponsor will continue to provide BN101/belumosudil 
medication at no cost until cGVHD progression, intolerable toxicity, initiation of a new cGVHD 
therapy, recurrence of hematological neoplasm, loss to follow-up, withdrawal of consent, or death, etc., 
whichever occurred first. During this period, subjects will return to the study center in accordance with 
their clinical practice, and the study will continue to collect SAEs, study drug use, and survival (or can 
be contacted by phone). In addition, SAEs for this group of subjects will need to be collected up to 28 
days (±7) after the last dose or the initiation of new cGVHD therapy. 
4.3.7 
Unscheduled visits 
During the study period, the investigator may decide whether to add unscheduled visits based on 
clinical needs (e.g., clinically significant laboratory test abnormalities, AEs, etc.). During unscheduled 
visits, the corresponding tests and AEs, etc. should be recorded in the original data and eCRF. If the 
same test is performed multiple times on the same day, only one set of test values (e.g., the earliest test 
result of the day) should be recorded in the eCRF, but all abnormal values of repeated tests should be 


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recorded in the eCRF. 
4.4 
Pharmacokinetic Sample Collection, Handling, Transportation, and Testing 
4.4.1 
Pharmacokinetic Sample Collection 
The first 12 subjects from the designated centers will be enrolled in the intensive PK blood 
collection program and the remaining subjects will be enrolled in the sparse PK blood collection 
program. 
The time points and allowed time windows for intensive PK blood collection and sparse PK blood 
collection are shown in Appendix 2 and Appendix 3, respectively. 
Subjects will be informed in advance that they will be required to take their study medication at 
the study center on the day of PK blood collection. The investigator will be required to keep a true 
record of the actual time of blood collection and sample number, and a protocol deviation report will 
be required for any blood samples collected outside of the allowed time window. 
4.4.2 
Pharmacokinetic Sample Handling, Storage and Transportation 
PK samples will be processed in accordance with the requirements of the Standard Operating 
Procedures of the Biological Sample Testing Unit or the laboratory manual provided by it. Each sample 
tube should be identified with a sample number and the subject number, initials, sample number, date 
and time of blood collection, and date and time of centrifugation should be detailed on the 
Pharmacokinetic Blood Sample Collection and Centrifugation Form. Note: Blood samples should be 
collected to avoid hemolysis as much as possible. 
Processed samples are stored frozen in accordance with the standard operating procedures of the 
biospecimen testing unit or the laboratory manual provided by the unit until they are shipped to the 
biospecimen testing unit. Transportation of samples is handled by a specialized cold-chain 
transportation company, which provides temperature data reports for the entirety of the sample 
shipment. 
Specific PK sample collection, handling, storage and transportation requirements are described 
in the SOPs of the biospecimen testing unit or in the laboratory manual provided by the unit. 
4.4.3 
Pharmacokinetic Sample Assays 
PK blood samples collected for the analysis of blood concentrations of BN101/belumosudil and 
its metabolites m1 and m2 were determined using a validated liquid chromatography-tandem mass 
spectrometry (LC-MS/MS) method. 
Methodology establishment, validation, and sample analysis will be performed by the biological 
sample testing unit. An analytical method validation plan will be developed, following the Guidelines 
for Validation of Methods for Quantitative Analysis of Biological Samples[20]and the relevant standard 
operating procedures of the testing unit. Methodological validation includes: selectivity, lower limit of 


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quantification and range of correction (standard curve performance), accuracy, precision, matrix 
effects, and stability of analytes in the biological matrix as well as in solution throughout storage and 
handling. Biological sample analysis will be performed according to the sample analysis plan and after 
completion of analytical method validation, PK blood samples will be pre-treated and assayed using 
validated LC-MS/MS methods. Biological sample reanalysis (Incurred sample reanalysis, ISR) will be 
performed in accordance with the appropriate guidelines and testing unit standard operating 
procedures. 
The establishment and validation of specific biological sample analysis methods are described in 
the Biological Sample Analysis Program. 
5. STUDY TREATMENT 
5.1 
Name of drug, physical and chemical properties, character, specification, composition, 
usage, packaging, storage 
5.1.1 
Investigational product 
Chinese name: BN101/belumosudil tablets 
Chinese Pinyin: BN101/belumosudil Pian 
Trade name: To be decided 
Dosage form: Tablet 
Manufacturer: UPM Pharmaceuticals, Inc. 
Sponsor: BK Pharmaceuticals Ltd. 
Agent: BioNova Pharmaceuticals (Shanghai) Ltd. 
Ingredients: BN101/belumosudil-, microcrystalline cellulose, hydroxypropylmethylcellulose, crosslinked 
sodium carboxymethylcellulose, anhydrous colloidal silicon dioxide, magnesium stearate, and 
Obadiol II (yellow 85F32410) 
Specification: 200 mg (tablets equivalent to 200 mg BN101/belumosudil free base) 
Storage
conditions: 
Store below 25°C 
Expiry date: 24 months tentatively 
5.1.2 
Control drug 
There is no control drug in this trial. 
5.2 
Method of administration 
Take orally with meals or within 5 minutes after meals, once daily for 28 days. 
5.3 
Drug packaging 
Labels are designed and drug packaging and labeling are performed by the sponsor and CRO for 
all study drugs in accordance with the Good Clinical Practice (GCP) and applicable national 
regulations. Subject number and visit number are also included in the labeling to facilitate drug 


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distribution, recall and statistics. Spare medications should be prepared and used only when the original 
medication to be used is not suitable for re-use (e.g., lost, soiled, etc.). 
5.4 
Drug labeling 
Drug labeling includes at least the following: 
• Drug for clinical trials only  
• Manufacturer, sponsor and agent 
• Protocol number 
• Subject number 
• Storage conditions 
• Expiry date 
• Dosage 
• Product batch number 
A sample label is shown below: 
Packaging specification 30 tablets/bottle Packaging label 
Name: BN101/belumosudil Tablets, 200 mg Subject ID：            
Protocol Number：BN101-201 
Direction for Use: Oral,   Day,   Tablets Each Time 
Batch No.：             
For Clinical Trial Use Only 
Package： 30 Tablets/Bottle 
Strength：200 mg 
Product Date：            
Keep Away from Children 
Storage Condition：Store below 25°C 
Expired Date：            
Sponsor：BK Pharmaceuticals Ltd.               Agent：BioNova Pharmaceuticals (Shanghai) Ltd. 
 
5.5 
Drug Distribution, Recording and Recovery 
The study drugs used in this trial will be provided free of charge by the agent [BioNova 
Pharmaceuticals (Shanghai) Ltd.] and will be distributed to each research center according to the plan, 
and each clinical research center will assign a person to be responsible for receiving, storing, 
distributing, recovering the study drugs and the corresponding records. The drug administrator or 
investigator of each research center is required to store sufficient study drugs according to the sponsor's 
recommendation and distribute them according to the requirements of the protocol. 
The management of investigational drugs at each clinical research center should meet the 
following requirements: 
1) A dedicated person (e.g., pharmacist) is responsible for receiving investigational drugs and 
supplies provided by the agent; 
2) complete records are required for the receipt, distribution, and use of investigational drugs and 
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3) The study drugs and supplies should be stored in a reasonable and safe manner; 
4) The investigational drug should only be prescribed by the Principal Investigator or a research 
physician authorized by the Principal Investigator; 
5) The investigational drug should only be distributed to eligible subjects in accordance with the 
protocol; 
6) Investigators should keep empty packages of used medications and unused medications for 
monitoring and retrieval by the monitor. 
7) After counting the medication at the visit, the loss of medication needs to be recorded in detail. 
Overdose of medication, misuse of medication, omission of administration of medication, and loss 
of medication need to be recorded in the original medical record. 
During the study period, the investigator should follow up on the subjects' medication intake to 
ensure that the subjects are taking the study medication correctly; and remind the subjects of the 
expiration date of the medication to ensure that the subjects are taking the medication within the 
expiration date. The investigator should keep a detailed record of the number of medications used by 
the subject and determine the subject's adherence to the medication. 
Used drugs, empty packages, etc. are counted by the supervisors and may be disposed of by the 
research centers as medical waste or destroyed according to the standard operating procedures in effect 
at each research center. Unused and expired medications are collected by the sponsor. 
At the end of the trial, the record of study drug shipments must be consistent with the quantities 
used and destroyed/returned, and any discrepancies need to be documented with the reason for the 
discrepancy. 
6. Treatment of subjects 
6.1 
Dose Adjustment 
Subjects who experience any clinically significant toxicity during treatment will need to be 
considered for suspension or termination of study drug therapy. Subjects who experience an AE related 
to study treatment may be dosed according to Table 3. 
Table 3 BN101/belumosudil dose adjustment 


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Toxicity  
Dose Adjustment 
≥ grade 3 
hepatotoxicity
（ALT/AST/TBIL） 
• 
Suspend BN101/belumosudil administration; 
• 
Within 14 days§toxicity does not return to ≤ Grade 1 or baseline level, then 
discontinue BN101/belumosudil therapy; 
• 
Within 14 days§toxicity returns to ≤ Grade 1 or Baseline level, resume 
BN101/belumosudil administration at a reduced dose level [e.g., 200 mg QD → 
200 mg once every other day (QOD)]; If the reduced dose level is administered for 
one full treatment cycle tolerated by the subject without recurrence of Grade 1 or 
greater hepatic function abnormality, return the dose to the original level for the 
following treatment cycle[e.g., 200 mg QOD → 200 mg QD]；  
• 
If this toxic reaction recurs after the reduced dose level, terminate 
BN101/belumosudil treatment. 
Other ≥ grade 3 
clinically significant 
toxicity associated 
with 
BN101/belumosudil 
• 
Suspend BN101/belumosudil administration; 
• 
Within 14 days§toxicity does not return to ≤ Grade 1 or baseline level, then 
discontinue BN101/belumosudil therapy; 
• 
Within 14 days§toxicity returns to ≤ Grade 1 or baseline level, then 
BN101/belumosudil administration is resumed at a reduced dose level [e.g., 200 
mg QD → 200 mg QOD]; if the reduced dose level is administered for a full 
treatment cycle as tolerated by the subject, and there is no recurrence of Grade 1 
or higher of this abnormality, then the next cycle of treatment the dose will be 
restored to the original level [e.g., 200 mg QOD → 200 mg QD]; 
• 
If the toxic reaction recurs after administration at a reduced dose level, 
BN101/belumosudil treatment will be discontinued. 
 Severity of toxicity was determined according to NCI CTCAE v5.0. 
§The maximum time allowed for suspension of BN101/belumosudil administration due to toxicity was 14 days, and subjects who 
discontinued for more than 14 days were required to withdraw from the study.If a subject can tolerate 1 full cycle of treatment after 
a BN101/belumosudil dose reduction, the dose may be restored to the dose prior to the reduction for the next cycle. 
6.2 
Management of Missed Doses 
Subjects should endeavor to take the study drug at the same time each day as prescribed by the 
protocol. 
If vomiting occurs after taking BN101/belumosudil and an insufficient dose of study drug is 
administered, no make-up dose is required. It is sufficient to continue to take the prescribed dose the 
following day. 
Subjects who noticed a missed dose of study medication were allowed to take one make-up dose 
of the current dose if it was more than 12 hours before the next dose and still take the prescribed dose 
on the following day; if it was less than 12 hours before the next dose, there was no make-up dose of 
the current medication, and the dose was still taken on the following day. 
6.3 
Management of Overdose 
An overdose dose of BN101/belumosudil has not been established. In clinical studies of 
BN101/belumosudil, a 500 mg BID dose of BN101/belumosudil given to healthy volunteers for 28 
consecutive days was well tolerated, suggesting that the drug has a wide safety window and that 
overdose is unlikely. There is no known antidote for BN101/belumosudil and no specific treatment 
recommendations in case of suspected overdose. Investigators should exercise comprehensive 
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The reporting and management of overdose is detailed in Section 8.9. 
6.4 
Combinations of medications and treatments 
All comorbid medications and treatments during the study period are to be documented. If a new 
systemic cGVHD treatment is initiated during the study period it will be considered as initiation of a 
new cGVHD treatment and will be considered as a failure of BN101/belumosudil treatment. 
6.4.1 
Corticosteroids 
Therapeutic doses of corticosteroids are to be collected throughout the study. After≥2 weeks of 
BN101/belumosudil use, the dose of corticosteroids may be reduced at the discretion of the investigator. 
A transient increase in corticosteroid dose (no more than 1 mg/kg/day prednisone equivalent) is 
permitted during cGVHD episodes, but this dose must be adjusted to the pre-enrollment dose level 
within 6 weeks. If the dose remains elevated for more than 6 weeks, it will be considered a 
BN101/belumosudil treatment failure. The occurrence of more than 2 episodes of cGVHD requiring 
an increase in corticosteroid dose during the first 6 months of BN101/belumosudil treatment will also 
be considered a BN101/belumosudil treatment failure. 
If the planned response assessment falls during a cGVHD episode of treatment, this response 
assessment will still be performed as planned, but the assessment will not be included in the primary 
efficacy analysis. 
6.4.2 
Systemic cGVHD Therapies 
Per the eligibility criteria, subjects receiving standard of care systemic cGVHD therapies such as 
calcineurin inhibitors (tacrolimus, cyclosporine), sirolimus, MMF, methotrexate, rituximab or ECP, 
may be enrolled if they have been on a stable dose/schedule. During the study treatment period, it is 
permissible to continue cGVHD treatment as described above at doses/regimens that have stabilized 
prior to enrollment, but it is not permissible to increase the dosage of these medications unless the 
increase in dosage is used only to maintain the current therapeutic level of the medication (e.g., to 
maintain the current blood concentration).Doses and schedules of these therapies will be collected 
throughout the study and changes will be documented. 
6.4.3 
Topical / Organ Specific Therapies for cGVHD 
Use of topical / organ specific therapies for cGVHD is permitted and must be documented 
(Includes name of drug, dose administered, site of administration, reason for administration, etc.) 
6.4.4 
Proton Pump Inhibitors 
The use of proton pump inhibitors (e.g., rabeprazole, omeprazole) is permitted only for short 
periods (no more than 1 week) during study treatment. 


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6.4.5 
CYP 3A4 Inhibitors / Inducers 
CYP3A4 inducers (e.g., rifampicin, phenobarbital) are prohibited during study treatment, and 
CYP3A4 inhibitors should be used with caution. A list of CYP3A4 inducers/inhibitors is detailed in 
Appendix 12. 
6.4.6 
CYP1A2 Inhibitors / Inducers 
CYP1A2 inhibitors / inducers should be used with caution. A list of CYP1A2 inducers/inhibitors 
is detailed in Appendix 13. 
6.4.7 
Drugs Prolonging the QTc Interval 
Drugs that prolong QT/QTc should be used with caution. A list of drugs that prolong the QT/QTc 
interval is detailed in Appendix 14. 
6.4.8 
Other Prohibited Combination Medications 
The use of systemic immunosuppressive drugs against cGVHD (including rituximab, ruxolitinib, 
ibrutinib, etc.) or other clinical trial medications is prohibited during study treatment. 
Tobacco, alcohol, and caffeinated beverages or foods are prohibited on the day of PK sample 
collection. 
6.5 
Treatment Compliance 
The investigator shall emphasize adherence to the subject during the informed consent 
conversation. During the course of the trial, if subjects' compliance is poor, the investigator should find 
out the reasons and actively take appropriate measures (e.g., emphasize the importance of protocol 
compliance to the subjects), and keep a complete record of the non-compliance, the reasons, and the 
appropriate measures taken. 
The investigator or other study personnel authorized by the investigator shall keep timely and 
accurate records of the quantity of study medication dispensed/recovered to/from each subject, the date, 
and the actual amount taken to ensure that subjects are taking the medication as prescribed by the 
protocol. The actual amount taken should be consistent with the dose required by the protocol. Subjects 
will be required to accurately complete a medication diary card. 
Subjects' medication adherence will be calculated for this study based on the number of 
medications dispensed/recalled: 
Compliance = Actual amount of medication taken by the subject
amount of medication to be taken by the subject  × 100% 
7. Study endpoints/indicators 
7.1 Efficacy endpoints/indicators 


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7.1.1 
Primary efficacy endpoints/indicators 
The primary efficacy endpoint is the overall response rate (ORR). Responders include subjects 
that achieve a [PR+CR]. Responses are defined by the 2014 National Institutes of Health (NIH) 
Consensus Development Project on Clinical Trials in cGVHD. 
Assessment of cGVHD response will be performed on Day 1 of Cycles 2 to 5 and on Day 1 of 
every 2 cycles thereafter (i.e., Day 1 of Cycles 2, 3, 4, 5, 7, 9, 11, etc.). As far as possible, the same 
investigator performed the response assessment on the subjects. 
Overall response will be assessed using a total score of 10 systems (including skin, eye, mouth, 
esophagus, upper gastrointestinal tract, lower gastrointestinal tract, liver, lungs, joints and fascia, and 
overall severity score). Overall response at each assessment time point will be categorized as CR, PR, 
or Lack of response (LR), where LR includes unchanged (LR-U), mixed (LR-M), or progressive (LR-
P) (see Table 4). The above assessments were based on NIH consensus criteria (2014). 
Table 4 cGVHD Response Definitions 
Response 
Definition 
Complete Response (CR) 
Resolution of all manifestations of cGVHD in each organ or site 
Partial Response (PR) 
Improvement in at least one organ or site without progression in any other organ 
or site 
Lack of Response (LR) 
Mixed (LR-M) 
Complete or partial response in at least one organ accompanied by progression in 
another organ* 
Unchanged (LR-U) 
Outcomes that do not meet the criteria for complete response, partial response, 
progression or mixed response 
Progression (LR-P) 
Progression in at least one organ or site without a response in any other organ or 
site 
* Considered progression for purposes of analysis 
Pulmonary function testing is required (FEV1) for this assessment. The same equipment and tester 
should be used during the course of the study to the extent possible. Pulmonary function tests should 
be conducted in accordance with study guidelines and the American Thoracic Society/European 
Respiratory Society standardization[21]of lung function testing. The normal expected value and the 
lower limit of the normal expected value of spirometry (including FEV1 and FVC) are recommended 
to refer to our normal expected value and the lower limit of the normal expected value of spirometry 
based on 7115 cases of people aged 4-80 years in 6 administrative regions of China for judgment [22,23] . 
7.1.2 
Secondary efficacy endpoints/indicators 
Secondary efficacy endpoints included median Duration of Response (DOR), Change in Lee 


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Symptom Scale Score, Response rate by organ system, Percentage of subjects with best efficacy as PR 
and percentage of subjects with best efficacy as CR, Change in corticosteroid dose, Change in CNI 
dose, Failure-Free Survival (FFS), Overall Survival (OS), Change in cGVHD severity based on the 
Physician-Reported Global cGVHD Activity Assessment, and Change in symptom activity based on 
cGVHD Activity Assessment Patient Self-Report. 
Lee Symptom Scale Score 
Changes in symptom burden/bother will be explored using the Lee cGVHD Symptom Scale 
(Appendix 7). Symptom burden will be assessed on Screening/Day 1 of each cycle starting on Cycle 
1 Day 1, as well as at the EOT visit. The questionnaire asks subjects to indicate the degree of bother 
that they experienced due to symptoms in seven domains potentially affected by chronic GVHD (skin, 
eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The degree to which 
subjects report that they are bothered by a symptom represents a global assessment incorporating not 
only the intensity of the symptom and its frequency, but also the degree to which it causes emotional 
disturbance or interferes with functioning. 
cGVHD Activity Assessment – Patient Self Report (Appendix 9) 
Changes in the cGVHD Activity Assessment – Patient Self Report will be evaluated. 
Change in Corticosteroid Dose 
The change in systemic corticosteroid dose over time will be determined. If subjects are not using 
prednisone as the corticosteroid therapy, then the prednisone dose equivalent will be determined. See 
Appendix 15 for specific corticosteroid equivalent dose conversions. 
Failure Free Survival (FFS) 
FFS is defined as the absence of cGVHD treatment change, non-relapse mortality and recurrent 
malignancy. 
7.1.3 
Exploratory Endpoints 
The PROMIS Physical Psychological Functioning Global Health Score (Appendix 8) will be 
evaluated as an exploratory efficacy endpoint for this study. 
7.2 
Safety Endpoints/indicators 
Safety endpoints included change from baseline in vital signs, physical examination, laboratory 
tests (including blood routine, blood biochemistry, and urinalysis), 12-lead electrocardiogram 
[including Bazetts' formula-corrected QT interval (QTcB) and QTcF means and maxima], as well as 
AEs, including SAEs, and AEs related to study drug. 
AEs (including SAEs) as well as abnormal laboratory findings will be categorized for severity 
according to NCI CTCAE v5.0. 


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Safety assessments are conducted throughout the study and, unless otherwise indicated, safety 
assessments begin with the signing of the ICF and continue until the end of safety follow-up after 
discontinuation of study drug [i.e., during the main study period, 28 ± 7 days after the final study drug 
administration or prior to initiation of a new treatment for systemic cGVHD, whichever occurs first]. 
For subjects who continue to receive study medication after the end of the subject's study, SAEs 
occurring during this period will continue to be collected from the subject [until 28 ± 7 days after the 
final study medication is administered or before starting new treatment for systemic cGVHD, 
whichever occurs first]. 
7.3 
PK Endpoints/indicators 
PK parameters include Cmax, time to peak (Tmax), elimination half-life (T1/2), area under the 
concentration-time curve from time 0 to the time of the last measurable concentration (AUC0-t), area 
under the blood concentration-time curve from initiation of dosing to the extrapolated infinite time 
(AUCinf), apparent clearance (CLz/F), and apparent volume of distribution (Vz/F), clearance rate 
constant (Kel), steady-state trough concentration (Cmin,ss), steady-state peak concentration (Cmax,ss), 
steady-state mean blood concentration (Cav,ss), steady-state accumulation ratio expressed as AUC0-t 
(RAUC1), steady-state accumulation ratio expressed as AUCinf (RAUC2), and steady-state accumulation 
ratio expressed as Cmax (RCmax). If the metabolites m1 and m2 of BN101/belumosudil can be detected 
and characterized, the ratios of the molecular weight-adjusted metabolites (m1 and m2) to the prodrug 
(P) Cmax and AUC (AUC0-t, AUCinf) also need to be calculated. 
8. Safety assessment 
Assess the safety of the subject from the time of signing the ICF to 28 days after the last dose of 
study drug according to NCI CTCAE v5.0. The following data need to be recorded for drug safety 
assessment: 
 
AE/SAE、AE related to study drug 
 
Laboratory Data 
 
Physical examination 
 
Vital signs 
 
12-lead electrocardiogram 
8.1 
Vital Signs 
Seated pulse rate and blood pressure measurements will be performed as outlined in the schedule 
of assessments (Appendix 1). Measurements will be taken with the subject sitting, having rested in this 
position for at least 5 minutes. Vital signs should be taken before ECGs and other scheduled 
assessments. Respiratory rate and temperature will also be measured. 


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8.2 
Physical examination 
Physical examination was performed according to the study assessment schedule (Appendix 1), 
assessing by organ and system, with a comprehensive physical examination including: height, general 
condition, head and neck, lymph nodes, skin, chest, abdomen, musculoskeletal system (including limbs 
and spine), and nervous system. 
8.3 
Twelve-lead ECG 
Twelve-lead ECGs will be performed as outlined in the schedule of assessments (Appendix 1). 
ECGs will be recorded after the subject has rested in the supine positon for at least 5 minutes. ECGs 
should be performed prior to any blood sample collections. When triplicate measurements are required, 
they should be taken at 1-2 minute intervals. Abnormalities in the ECG that lead to a change in subject 
management (e.g., dose delay, need for additional medication or monitoring) or result in clinical signs 
and symptoms are considered clinically significant for the purposes of this study and will be recorded 
in the AE eCRF. If ECG abnormalities meet criteria defining them as serious, they must be reported as 
an SAE (See specifically Section 8.6.2.2). 
8.4 
Clinical Laboratory Parameters 
Clinical laboratory tests will be performed as outlined in the schedule of assessments (Appendix 
1). Samples should be taken predose. Specific inspections are listed in the table below. 
Table 5 Clinical Laboratory Tests 
Name of Test 
Content of Test 
Blood routine 
Hemoglobin (Hb), Erythrocyte Compaction (HCT), Red Blood Cell Count (RBC), White 
Blood Cell Count (WBC), Leukocyte Sorting Count (including Neutrophils, Lymphocytes, 
Monocytes, Basophils, Eosinophils), Platelets (PLT) 
Urine routine 
pH, urinary protein (U-PRO), urinary white blood cells (U-WBC), urinary red blood cells 
(U-RBC), urinary glucose (U-GLU), urinary occult blood, urinary chologen, urinary 
bilirubin, urinary nitrites, and urinary ketone bodies (U-KET) 
Blood 
biochemistry 
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase 
(ALP), lactate dehydrogenase (LDH), gamma-glutamyltransferase (gamma-GGT), total 
bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB), total protein (TP); creatinine 
(sCr), urea (Urea) or urea nitrogen (BUN), uric acid (UA), potassium (K), sodium (Na), 
chlorine (Cl), calcium (Ca), phosphorus (P), magnesium (Mg), blood glucose (GLU) 
Virology 
Hepatitis B Surface Antigen (HBsAg), Hepatitis B Surface Antibody (HBsAb), Hepatitis B 
Core Antibody (HBcAb), Hepatitis B e Antigen (HBeAg), Hepatitis B e Antibody (HBeAb), 
Hepatitis C Antibody (HCV-Ab), Human Immunodeficiency Virus (HIV) Antibody, 
Hepatitis B Virus DNA (HBV-DNA) (if applicable), Hepatitis C Virus RNA (HCV-RNA) (if 
applicable) 
Abnormalities in clinical laboratory tests that lead to a change in subject management (eg, dose 
delay, requirement for additional medication or monitoring) are considered clinically significant for 
the purposes of this study and will be recorded on the AE eCRF page. Laboratory results will be 
classified using the CTCAE v5.0. If laboratory values constitute part of an event that meets criteria 


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defining it as serious, the event (and associated laboratory values) must be reported as an SAE (see 
Section 8.6.2.2). 
8.5 
Pregnancy Testing 
Pregnancy testing is performed only on women of childbearing age. Urine pregnancy testing is 
optional except during the screening period when serum pregnancy testing is mandatory, but a positive 
urine pregnancy test result needs to be confirmed by serum pregnancy testing. 
8.6 
Adverse Event 
8.6.1 
Definition 
8.6.1.1 Adverse Event 
An adverse event (AE) is any adverse medical event that occurs in a subject following the use of 
an investigational drug, whether or not causally related to the study drug or study procedure. Thus, an 
AE can be any adverse or undesired sign, symptom, or disease, including AEs related to the study drug, 
significant laboratory outliers, new diseases that develop during the study period, and exacerbations of 
pre-existing diseases or symptoms prior to the trial (excluding the disease for which the test drug is 
intended to treat). 
In this study, any event that is clearly caused by progression of the disease (any degree or 
exacerbation of symptoms expected from the proposed treatment of the disease) is not reported as an 
AE, with the exception of deaths due to disease progression. Deterioration of the studied disease 
condition at a rate greater than expected should be reported as an AE. 
The investigator is responsible for assessing the relationship between all AEs and the study drug. 
However, the Principal Investigator may delegate judgment to other qualified clinicians who are 
participating in this study but remain responsible for it. The investigator must provide a list of those 
who are appropriately qualified and accept the delegation. 
Pre-Treatment Event 
A pre-treatment event (PTE) is any adverse medical event that occurs after a clinical study subject 
signs an ICF and before the first study drug is administered; the event is not necessarily causally related 
to participation in the study. 
Other points to consider for pre-treatment events and adverse events 
An unfavorable outcome may usually be: 
• 
Indicate a new diagnosis or an unintended worsening of a preexisting condition (intermittent 
events due to a preexisting underlying condition should not be considered a PTE or AE). 
• 
necessitate therapeutic intervention. 
• 
Invasive diagnostic procedures are required. 
• 
The need to discontinue or change the dose of the study drug or concomitant medication. 


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• 
The investigator considers it an unfavorable outcome for any reason. 
• 
PTE/AEs resulting from study procedures (e.g., bruising after blood collection) should be 
recorded as PTE/AEs. 
Diagnostic Comparison Signs and Symptoms: 
Each event should be recorded as a single diagnosis and accompanying signs or symptoms should 
not be recorded as a separate AE. If the diagnosis is unknown, the signs or symptoms may be recorded 
as a PTE or AE accordingly. 
In general, AEs that are secondary to other events (e.g., caused by other events or clinical sequelae) 
should be documented as their primary event unless the secondary event is of severe magnitude or is 
an SAE. however, clinically significant secondary events that occur at a different time than the primary 
event should be documented as separate AEs in the eCRF. if the correlation between the events is 
unclear, they should be separately Recording. 
Laboratory test values, vital signs, and ECG results: 
Abnormal laboratory tests, vital signs, and electrocardiogram results that meet one of the 
following criteria will be documented as AE: 
• 
Progression from baseline indicators with clinical symptoms; 
• 
Resulting in a change in study medication (e.g., dose adjustment, temporary or permanent 
discontinuation, etc.); 
• 
Requires medical intervention or change in combination therapy; 
• 
Clinically significant in the judgment of the investigator. 
If clinically significant abnormal laboratory tests, vital signs, or electrocardiogram results are 
symptomatic of a disease or syndrome (e.g., cholecystitis resulting in elevations of alkaline 
phosphatase and bilirubin greater than 5 times the upper limit of normal), record the diagnosis (i.e., 
cholecystitis) on the AE form of the eCRF only. Instead, record an abnormal laboratory test or 
abnormal vital sign on the AE form of the eCRF and indicate whether the test value is above or below 
the normal range (e.g., record "elevated potassium" rather than "abnormal potassium"). If a laboratory 
test abnormality or vital sign abnormality has a standardized clinical term, the clinical term should be 
recorded in the eCRF (e.g., an elevated potassium level of 7.0 mmol/L should be recorded as 
"hyperkalemia"). If the same clinically significant laboratory test abnormality or vital sign abnormality 
is observed over multiple follow-up visits, it should be documented in the eCRF on a case-by-case 
basis according to a graded change in the severity of the abnormality or a change in the etiology of the 
abnormality. 
Pre-existing diseases： 


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• 
Pre-existing diseases (present at the time of signing the ICF) are considered concomitant 
conditions and should not be recorded as PTE or AE. Baseline evaluations (e.g., laboratory 
tests, electrocardiograms, echocardiograms, etc.) should not be recorded as a PTE unless they 
are related to study operations; however, if a subject has a worsening of such concomitant 
condition or develops a complication, the worsening or complication should be recorded 
accordingly as either a PTE (the worsening or complication occurs prior to the initiation of 
the administration of the study drug) or an AE (the worsening or complication occurs after 
the initiation of the study drug). The investigator should ensure that the terminology of the 
recorded event reflects the change in the condition (e.g., "worsening of ..."). 
• 
If the subject has a pre-existing intermittent condition (e.g., asthma), the episode should be 
recorded as a PTE/AE only if the episodes become more frequent, severe, or exacerbated, 
i.e., the investigator should ensure that the terminology of the recorded AE describes the 
change in the condition relative to baseline (e.g., "...the worsening"). 
• 
If the subject has a degenerative concomitant condition (e.g., cataracts, rheumatoid arthritis), 
worsening of the condition should be recorded as a PTE/AE only if the condition worsens 
more than expected. In addition, the investigator should ensure that the recorded AE 
terminology describes the change in the condition (e.g., "...the worsening"). 
persistent or recurrent AE: 
• 
A persistent AE is an AE that persists in the subject without remission between evaluation 
time points. This AE is recorded only once on the eCRF. The initial severity of the event 
should be recorded and updated as the event worsens to record the worst severity of the event. 
• 
Recurrent AE is defined as an AE that has resolved between the two evaluation time points 
but then occurs again. the occurrence of the event should be documented separately in the 
eCRF. 
Pre-planned surgery or operation: 
• 
Pre-planned operations (surgical or therapeutic) scheduled prior to the signing of the ICF are 
not considered PTEs or AEs; however, if a pre-planned operation is performed earlier due to 
a worsening of a pre-existing condition (e.g., as an emergency), the worsening of the 
condition should be documented accordingly as a PTE or an AE.Complications resulting 
from any planned operation should be reported as an AE. 
• 
Elective Surgery or Operations: Elective surgery or operations performed in the absence of a 
change in the subject's condition should not be reported as a PTE or AE but should be 
documented in the subject's original data. Complications resulting from elective surgery 
should be reported as an AE. 


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8.6.1.2 Significant Adverse Events  
A significant adverse event is defined as any occurrence of an AE and apparent abnormality in 
hematology or other laboratory tests, other than SAEs, that results in the use of targeted medical 
measures (e.g., discontinuation of medication, dose reduction, and symptomatic treatment). 
8.6.1.3 Adverse Events Associated with Investigational Drugs 
A new drug or a new use of a drug that produces a harmful or undesired, causally related reaction 
to the application of the drug at any dose during pre-approval clinical investigational dosing, especially 
during a period when therapeutic doses have not yet been established, should be considered an 
Investigational Drug-Related AE. In determining that an AE is an investigational drug-related AE, 
there must be at least a reasonable likelihood that there is a correlation between the AE and the 
investigational drug, i.e., the AE needs to be considered to be an investigational drug-related AE in all 
cases where the possibility of a correlation cannot be ruled out.Refer to section 8.6.1.5 below for the 
criteria for determining causality between an AE and an investigational drug. 
8.6.1.4 Serious Adverse Events 
A serious adverse event (SAE) is defined as an AE that occurs during any phase of the study (i.e., 
Screening, Treatment, Follow-Up), at any dose of study drug, and that meets one or more of the 
following criteria: 
 
Leading to Deatha 
 
Life-threatening adverse eventb 
 
Inpatient hospitalization or prolongation of existing hospitalizationc 
  Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functionsd 
 
Congenital anomaly/birth defecte 
 
Important medical eventf 
For example, significant medical events that are not immediately life-threatening, or fatal, or that 
require hospitalization, but that jeopardize the subject, or that require medical intervention to prevent 
the above outcomes, require immediate scientific medical judgment and a decision on whether to report 
them expeditiously. These should also be considered SAEs. 
SAEs are further explained below:  
a 
AE resulted in the death of the subject. 
b 
The occurrence of an AE that immediately poses a risk of death to the subject. Excludes those 
AEs that may result in death after severe progression, e.g., drug-induced hepatitis without 
liver failure. 
c 
Any AE that results in hospital admission and prolonged hospitalization. excluding 


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conditions such as elective surgery or admission for tests decided prior to the trial and for 
which the course of treatment was not altered during the course of the study. 
d 
Any AE that results in injury, impairment, or disruption of the subject's functioning and/or 
physiological structure, physical activity, or quality of life. 
e 
Suspicion that exposure of either parent to the study drug will result in adverse outcomes in 
offspring. 
f 
A significant medical event that, although not immediately life-threatening, resulting in death 
or hospitalization, may, in the medical judgment of the subject, expose the subject to injury 
or require medical intervention to prevent the occurrence of the conditions listed above, 
which includes, but is not limited to, a medical event that does not result in hospitalization, 
but that requires intensive treatment for anaphylactic bronchospasm, malignant hemorrhagic 
disease, or convulsions, either in the emergency room or at home. 
In this study, any serious event (other than death) that is clearly due to progression of disease (any 
degree or exacerbation of symptoms expected from the disease to be treated) is not recorded and 
reported as an SAE. 
8.6.1.5 Relationship to Study Drug 
The causal relationship of an AE to the study drug is categorized as definitely related, probably 
related, probably unrelated, definitely unrelated, and undeterminable. Of these, definitely related, 
possibly related, and undeterminable are considered to be related to the study drug. 
Table 6 Determination of causal relationship between adverse events and study drugs 
definitely 
related 
The time sequence between drug use and the onset of the AE is reasonable; the AE stops, or 
rapidly decreases or improves, after discontinuation of the drug; with reuse, the AE recurs and 
may be markedly worse (i.e., a positive re-excitation test); the event is consistent with the type 
of AE known to be associated with the investigational drug for the drug under suspicion; and 
the influence of other confounding factors, such as the original disease, has been ruled out. 
probably 
related 
The timing of the reaction is consistent with the chronological order of administration of the 
drug, the reaction is consistent with the type of reaction known to occur with the study drug, 
and the subject's clinical status or other therapeutic modalities are likely to produce the 
reaction. 
probably 
unrelated 
The timing of the reaction does not correspond to the chronology of the administration of the 
drug, the reaction is not quite consistent with the type of reaction known to occur with the 
investigational drug, and the subject's clinical status or other therapeutic modalities may have 
produced the reaction. Possibilities related to medication administration cannot be ruled out. 
definitely 
unrelated 
The timing of the reaction does not correspond to the chronological order of administration of 
the drug, the reaction has a type of reaction consistent with that known for non-study drugs, 
the subject's clinical status or other treatment modalities may also produce the reaction, the 
reaction is eliminated by improvement in disease status or cessation of other treatment 
modalities, the reaction occurs with repeated use of other treatments, and there is a strong 
correlation with other risk factors. 
undeterminable The timing of the reaction is not clearly related to the chronological order in which the 


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medication was administered, the reaction is similar to the type of reaction known to occur 
with the study medication, and other medications used at the same time may cause the same 
reaction without an adequate basis for judgment. 
AE：Adverse Events 
8.6.1.6  Criteria for Severity of Adverse Events 
The severity of an AE shall be documented in accordance with NCI CTCAE v5.0.The severity of 
an AE that is not identified in NCI CTCAE may be assessed according to the following scale: 
Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated; 
Grade 2: Moderate; minimal, localized or non-invasive interventions; age-related limitations in 
instrumental activities of daily living (ADLs) (instrumental ADLs are defined as 
cooking, grocery or clothing shopping, using the phone, money management, etc.); 
Grade 3: Severe or medically significant, but not immediately life-threatening; hospitalization or 
prolonged hospitalization; disability; limitations in self-ADLs (self-ADLs refer to 
bathing, dressing and undressing, eating, toileting, and taking medications, rather than 
being bedridden); 
Grade 4: life-threatening consequences; urgent intervention indicated; 
Grade 5: death related to AE. 
All AEs or other signs and symptoms that occur during the course of the study should be recorded 
on the AE page of the eCRF, regardless of whether it is related to the clinical trial. A record should be 
given for any AE in all subjects who are in the study period. 
8.6.1.7 Measures Related to Investigational Drugs 
 
Discontinuation – The study drug is permanently discontinued because of a specific AE. 
 
Dose Unchanged – No discontinuation of study drug is required for a specific AE. 
 
Unknown – Used only when the measure taken cannot be determined. 
 
Not Applicable – Discontinuation of the study drug for reasons other than the specific AE, 
e.g., the study was terminated, the subject died, the study drug was discontinued before the 
AE occurred. 
 
Dose Reduction– Dose reduction due to a specific AE. 
 
Dose Interruption –  Temporary interruption (suspension) (including subject-initiated 
interruption of dosing) of an investigational drug because of a specific AE and subsequent 
resumption of dosing. 
8.6.1.8 Outcome of Adverse Events 
The outcomes of AE can be described as follows: 


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 
Recovered/Resolved: the "(S)AE termination date" should be noted. 
 
Recovering/ Resolving: the event is still not fully resolved, but the subject is in the recovery 
phase. Follow-up visits are required. 
 
Not Recovered/Unresolved: the incident is ongoing. 
 
Recovered/Resolved with Sequelae: Only if the subject will have sequelae that will last for 
a long period of time or for life, e.g., blindness due to diabetes mellitus, hemiplegia due to 
stroke. The "(S)AE termination date" should be indicated. 
 
Fatal: "(S)AE termination date" should be noted. Time of death needs to be recorded when 
AE is fatal. 
 
Unknown: the AE was not known to the investigator, e.g., the subject was lost to follow-up. 
If the AE outcome is rated as "Recovering/Resolving", or "Not Recovered/Unresolved", or 
"Unknown", the AE termination date may be temporarily withheld. 
The date of termination of the AE must be recorded if the AE outcome is rated as 
"recovered/resolved" or "recovered/resolved with sequelae." 
All AEs must be followed to determine the final outcome until the event is resolved and the 
investigator considers the event to be stable or irreversible. 
When the subject completes the clinical study, the investigator should follow the outcome of the 
AE related to the study drug until the event is resolved and, in the opinion of the investigator, stabilized 
or irreversible. 
8.6.2 
Collection and reporting procedures 
8.6.2.1 Adverse Event Collection and Reporting 
PTE and AE collection period 
Collection of PTE will begin when the subject signs informed consent and continue until the 
subject first receives study drug or until screening failure. For subjects who withdraw from the study 
prior to study drug administration, PTE will be collected until the subject withdraws from the study. 
Collection of AEs will begin when the subject first receives study drug and continue until 28 ± 7 
days after the last dose of study drug or until initiation of new treatment for systemic cGVHD, 
whichever occurs first, whether or not related to study drug, and must be collected and recorded by the 
investigator. Only AEs/SAEs related to study treatment were collected and recorded 28±7 days after 
the last dose of study drug or after initiation of new systemic cGVHD treatment and were required to 
be followed until the event was resolved and the investigator considered the event to be stabilized or 
irreversible. 
The end date of the PTE/AE was the date when the event was resolved and deemed stable or 


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irreversible by the investigator. 
PTE and AE Reporting 
At each study visit, the investigator will assess whether a subjective AE has occurred.A neutral 
question may be asked, such as "How have you felt since your last visit?" . Subjects may report AEs 
that occur at any other time during the study. 
All PTEs occurring in subjects must be monitored until symptoms subside or until any clinically 
relevant changes in laboratory tests have returned to baseline, or until a satisfactory explanation for 
the change has been provided. Non-severe PTEs related or unrelated to study operations are not 
required to be followed up for study protocol purposes. 
All subjects experiencing AEs, whether or not related to study drug use, must be monitored until 
symptoms have subsided and any clinically relevant changes in laboratory test values have returned to 
baseline, or until a satisfactory explanation for the observed changes has been provided. 
All clinically significant laboratory test abnormalities confirmed by laboratory retesting will be 
followed until these abnormalities have returned to acceptable levels or have been satisfactorily 
explained. 
All PTEs and AEs that occur within the collection timeframe specified in this protocol must be 
fully documented on the PTE/AE page of the eCRF. The documentation must be supported by primary 
sources and should provide a detailed description of each incident, including the information listed 
below: 
 
Event terminology 
 
Start and end dates 
 
Severity 
 
Investigator's judgment of causal relationship (relevant or irrelevant) between the event and 
study drug administration (not required for PTE) 
 
Investigator's judgment of causal relationship between the event and study procedures, 
including details of suspected procedures 
 
Relevant measures taken with respect to the study drug (not applicable for PTEs) 
 
Event outcome 
Subject diaries and questionnaires will not be used as the primary means of collecting AEs. 
However, if the investigator identifies a potential AE through the information collected in these 
documents, the subject should be followed up appropriately for medical evaluation. Through this 
follow-up, if it is determined that a previously unreported AE has been identified, it should be reported 
following normal reporting requirements. 
8.6.2.2 Serious Adverse Event Collection and Reporting 


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For all any SAE that occurs within the collection timeframe specified in this protocol, the 
investigator must complete the Serious Adverse Event (SAE) Report Form provided by the sponsor or 
its representative, sign and date it, and report it to the sponsor and its representative by mail or fax 
immediately within 24 hours of being informed. 
Contact Information - The fax number and e-mail address of the sponsor or his/her representative 
will be kept in the investigator's folder at the research center. Questions regarding drug safety and 
pharmacovigilance can be contacted in the above manner. 
Table 7 Serious Adverse Event Reporting Units and Contact Information 
Reporting unit 
Fax/telephone/email 
Sponsor 
E-mail: yu.wang@bionovapharma.com； 
Tel: 18621889377 
Representative of the sponsor 
E-mail: Bionova_PV@ppccro.com 
SAEs should detail the description of symptoms, severity, time of onset, time of management, 
measures taken, time and mode of follow-up and regression. All SAEs should also be completed on 
the eCRF form at the same time, and it needs to be ensured that the information provided on the SAE 
reporting form is consistent with the data recorded in the eCRF about the event. 
The investigator must provide an assessment of the causal relationship of the event to the study 
drug at the time the SAE is reported. If the investigator is unsure whether the AE is an SAE, then it 
needs to be conservatively assessed as an SAE until its nature can be demonstrated. 
For all SAEs, the investigator needs to follow up until there are clear results to ensure that all 
problems are resolved. Administer necessary treatments and therapeutic measures during follow-up to 
ensure that subject harm is minimized and subject safety is adequately ensured. Detailed follow-up 
information is recorded (e.g., at the end of the study, whether special treatment is needed, whether 
hospitalization is required, etc.). 
The investigator is to submit a follow-up report to the sponsor until the SAE is resolved, the 
investigator 
believes 
the 
event 
has 
stabilized 
(returned 
to 
baseline 
levels, 
proven 
unresolvable/permanent), or is irreversible (death of the subject). In the case of permanent impairment, 
follow-up is to continue until the SAE is considered to have stabilized. 
8.7 
Death 
8.7.1 
Recording of Deaths 
All deaths occurring throughout the study period (including within 28 days of the last dose of 
study drug, and during the survival follow-up period), including deaths resulting from disease 
progression, must be recorded in the appropriate module of the eCRF. 
If the death of the subject occurs, the event is to be reported as an AE [if the death was due to 


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disease progression and the death cannot be attributed to any of the NCI CTCAE v5.0 Level 5 AEs, 
report the AE by disease progression with a severity level of Level 5, or, if the death of the subject was 
due to an AE (e.g., cardiac disease: cardiac arrest), report the death as a Level 5 for that AE], and 
Record the cause of death in the appropriate place on the eCRF. The investigator must determine the 
primary cause of death and appropriately categorize the reason for the subject's withdrawal from the 
trial. If the cause of death is unknown at the time of reporting, it should be recorded as "unexplained 
death" on the eCRF AE form and the exact cause of death should be further investigated. 
8.7.2 
Reporting of death 
The report of death should include information such as disease progression and primary or 
secondary cause of death, if any. An autopsy may be helpful in the assessment of the cause of death, 
and if an autopsy is performed, the report should include the results of the autopsy. 
Deaths must be reported as SAEs to the sponsor or its representative within 24 hours of 
notification by completing the Serious Adverse Event (SAE) Reporting Form and, in accordance with 
GCP requirements, the investigator should provide the sponsor and the Ethics Committee with other 
required information such as autopsy reports and final medical reports. Deaths to be reported include 
the following two: 
 
Deaths, whether or not related to the study drug, that occurred from the time the subject 
signed informed consent until 28 days after the last dose of study drug; 
 
Deaths that are definitely related or possibly related to the study drug after 28 days after the 
last dose of study drug (excluding deaths that are not related to the study drug). 
8.8 
Hospitalization 
In general, hospitalization is defined as remaining in an inpatient or emergency ward for 
observation or treatment (for more than 24 hours). An AE requiring hospitalization is considered a 
SAE. hospitalization or extended hospitalization for non-medical reasons/convenience, etc. or purely 
for the purpose of a clinical trial that does not meet the criteria for a medical event cannot be treated 
as a SAE. 
The following hospitalizations are not considered SAEs: 
 
Staying in an emergency room or other hospital department for no more than 24 hours that 
does not result in hospitalization (unless considered a medically significant or life-
threatening event); 
 
Hospitalization resulting from elective surgery that was planned prior to the signing of the 
ICF; 
 
Hospitalization resulting from a clinical trial protocol requirement; 


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 
Hospitalization resulting from a requirement for a health physical examination (e.g., routine 
colonoscopy); 
 
Hospitalization that is not for the purpose of disease treatment and was planned prior to 
enrollment and needs to be documented; 
 
Hospitalization not related to a health condition and not requiring medical/surgical 
intervention (e.g., lack of housing, financial hardship, need for patient care, family reasons); 
 
Hospitalization for Medicare reimbursement reasons. 
Hospitalization for elective surgery, routine clinical procedures, physical examination, admission 
for observation, or as required by the protocol, but not for AE, is not considered an AE, but is 
documented in the medical record. If an unanticipated event occurs during this process, it is reported 
as a "serious" or "non-serious" AE according to routine criteria. 
8.9 
Pregnancy 
Pregnancy in Female Subjects 
If a female subject becomes pregnant during the study (from the time of signing informed consent 
to 28 days after the last dose of study drug), a Pregnancy Report Form should be completed in the 
same timeframe as the SAE report, reported promptly to the Sponsor, and documented in the eCRF for 
follow-up of outcomes. 
Any occurrence during pregnancy of: spontaneous or induced abortion, birth defects or congenital 
malformations in the newborn, malformations and anomalies in stillbirths, and serious complications 
in the mother and newborn should be documented and reported as an SAE. 
During the study period, female subjects should discontinue the study drug as soon as they 
become pregnant and notify the investigator. The investigator should advise the subject and discuss 
the risks of continuing the pregnancy and possible effects on the fetus, and the subject must withdraw 
from the study. The investigator should continue to follow subjects until delivery and 30 days after 
delivery; subjects who fail to deliver will be followed until the end of the pregnancy. 
Pregnancy in the Spouse of a Male Subject 
If the spouse of a male subject becomes pregnant during the study period (from the time the male 
subject signs the informed consent to 28 days after the last dose of study drug), a Pregnancy Report 
Form should be completed in the same timeframe as the SAE report, reported promptly to the Sponsor, 
and documented in the eCRF for follow-up of the outcome. 
Any occurrence during pregnancy of: spontaneous or induced abortion, birth defects or congenital 
malformations in the newborn, malformations and anomalies in stillbirths, and serious complications 
in the mother and newborn should be documented and reported as SAEs. 
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the study period. The investigator should advise the subject and his/her spouse to discuss the risks of 
continuing the pregnancy and the possible effects on the fetus; male subjects do not have to withdraw 
from the study, but the investigator should continue to follow the subject's spouse until delivery and 
for 30 days after delivery, and in the case of those who fail to deliver, follow up until the end of the 
pregnancy is required. 
8.10 Overdose 
An overdose dose of BN101/belumosudil has not been determined. Overdose in this study is 
defined as the intentional or unintentional ingestion of more than the dose to which each subject was 
assigned according to the study protocol. For the purposes of this study, drug overdoses without clinical 
signs or symptoms will not be considered AEs. drug overdose-induced AEs will be documented on the 
AE page of the eCRF in accordance with Section 8.6.2.1 (Collection and Reporting of AEs). SAEs due 
to drug overdose will be reported according to the procedures described in Section 8.6.2.2 (Collection 
and Reporting of SAEs). 
There are no known specific antidotes for study drug overdose. If an overdose is suspected, 
supportive therapy should be given based on the subject's clinical condition. 
8.11 Rapid Reporting of Suspected Unexpected Serious Adverse Reaction by the Sponsor 
Sponsors are required to report Suspected Unexpected Serious Adverse Reactions (SUSARs) to 
the appropriate authorities on an expedited basis as an Individual Case Safety Report (ICSR) in 
accordance with the latest applicable regulations. The investigator should sign and read the relevant 
safety information of the clinical trial provided by the sponsor in a timely manner upon receipt and 
consider the subject's treatment, whether to adjust it accordingly, communicate with the subject as 
early as possible if necessary, and should report suspected unexpected serious adverse reactions 
provided by the sponsor to the ethics committee. 
The content of the ICSR should be reported in accordance with the requirements of the ICH 
《E2B(R3): Management of Clinical Safety Data: Data Elements for the Transmission of ICSR》. The 
terminology should be coded using ICH《M1: MedDRA》.SUSAR is defined as all unanticipated and 
serious adverse reactions occurring during a clinical trial that are definitely related to or suspected to 
be related to the test drug. 
An unexpected adverse reaction is an adverse reaction whose nature, severity, consequences, or 
frequency are different from the expected risks described in current information about the test drug 
(e.g., documents such as the investigator's brochure). The investigator's brochure serves as the primary 
document that provides the safety reference information used to determine whether an adverse reaction 
is expected or unexpected. Refer to Section 8.6 of this protocol for the determination of whether it is a 


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SAE and the determination of causality. For SUSAR, expedited reporting should also be performed 
when the sponsor and investigator cannot agree on the AE and drug causality determination, and either 
party determines that a relationship to the test drug cannot be ruled out. 
SAEs occurring at the end of the clinical trial or after the end of follow-up until the conclusion of 
the review and approval is obtained should be reported by the investigator to the sponsor, and should 
also be subject to expedited reporting if they are unexpected serious adverse reactions. Other situations 
where rapid reporting is required are: 
1) For known, serious adverse reactions with an increased incidence judged to be clinically 
important; 
2) where there is a clear hazard to the exposed population, e.g. where the drug is ineffective in 
the treatment of a life-threatening condition; 
3) Significant safety findings (e.g., carcinogenicity) in newly completed animal testing; 
4) information obtained by the sponsor from other sources about unexpected serious adverse 
reactions and other potentially serious safety risks associated with the investigational drug; 
5) When the sponsor and investigator cannot agree in the determination of causality between the 
AE and the drug, and in the judgment of either one of them, a correlation with the study drug 
cannot be ruled out. 
The following conditions are generally excluded from expedited reporting: 
1) Non-SAE; 
2) SAE not related to the test drug; 
3) Serious but expected adverse reactions; 
Please refer to the Standards and Procedures for Rapid Reporting of Safety Data During Drug 
Clinical Trials for specific reporting procedures. 
SUSAR Rapid Reporting Timeframe: 
1) For fatal or life-threatening SUSARs, sponsors should report as soon as possible, but no later 
than 7 days after first notification, and report, and complete follow-up information within the 
next 8 days. [Note: The day the sponsor is first notified is Day 0.] 
2) For non-fatal or life-threatening SUSARs, the sponsor shall report as soon as possible, but not 
more than 15 days, after initial notification. 
After the initial report, the sponsor should continue to follow up and report new information or 
changes to the previous report, etc., in a timely manner in the form of a follow-up report, with a 
reporting time limit of 15 days from the date the new information is obtained. 
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9.1 
Data Management workflow 
The study data management is the responsibility of the CRO Data Department to ensure the 
authenticity, integrity, privacy and traceability of clinical trial data. 
9.1.1 
Workflow 
 
9.1.2 
Role and Responsibility 
EDC Role 
Responsibility 
Clinical Research Coordinator 
(CRC) 
1) Data Entry 
2) Add comments  
3) Answer Query 
Sub Investigator (Sub-I) 
1) Data Entry 
2) Add comments  
3) Answer query 
4) Electronic signature 
Principal Investigator (PI) 
1) Data Entry 
2) Add comments  
3) Answer query 
4) Electronic signature 
Clinical Research Associate 
(CRA) 
1) Source data consistency check 
2) Send query 
Medical Monitor (MM) 
1) Send query 
Data Management (DM) 
1) Send query 
2) Answer query  
3) Freeze and Unfreeze data 


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EDC Role 
Responsibility 
Read-only 
1) Read-only 
Safty 
1）Send query 
Coder 
1) Send query 
9.2 
Database design and creation 
Construction of the eCRF database in the Medidata Rave system by the CRO Data Department 
shall comply with FDA 21 CFR Part 11. Data traces such as system entry, data entry, modification, or 
deletion should be managed in the database, and the establishment of the database should adopt the 
Clinical Data Exchange Standards Association (CDISC) standard. 
9.3 
Data Entry 
Information shall be entered into the EDC database by the Investigator or the site staff authorized 
by the Investigator as soon as possible after the completion of the visit, and the data entry shall be 
carried out in strict accordance with the principle of "what you see is what you record". After the 
original data is entered, any changes made to the eCRF are automatically recorded in the system. 
9.4 
Data verification 
Based on the finalized data verification plan, the data manager will set up a data logic verification 
process in the EDC system. 
Once the data are entered into the EDC system, if there is any illogical data, the system 
verification will kick in and trigger a query. These queries will need to be reviewed and answered by 
the investigator or site staff authorized by the investigator. When updated data make logical checks no 
longer valid, the data query is immediately closed; if the clinical center confirms the data and provides 
a response, the data manager is required to review the response information. When justified, the data 
query is closed; when the data issue is not resolved, the data administrator can continue to communicate 
with the clinical center by adding data queries until they are finally resolved. 
Subject data lists/reports are programmed to be generated to support manual data verification 
throughout the study. Manual challenges can be added to the EDC system when data arises that requires 
clarification/verification/confirmation by the investigator. Before locking the database, the data 
manager confirms that all queries have been resolved and the investigator completes an electronic 
signature in the EDC system to ensure the integrity and accuracy of the subject data in the EDC system. 
9.5 
Medical coding 
The Data Manager of the CRO Data Department is responsible for the medical coding of this 
study. Coding will include past medical history, concomitant medication and AE. 


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Medical history and AE will be coded according to the MedDRA dictionary (version 20.1 or 
above), and concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHO DD), and the dictionaries used will be the versions confirmed by the sponsor. 
During the coding process, any data issues that could not be coded due to inappropriate, inaccurate, 
or ambiguous provision of medical terminology would be requested by the data manager to be verified 
and confirmed by the investigator in the form of a data query. 
Prior to database lock, the data manager sends a medical coding report to the sponsor and is 
required to be reviewed by the sponsor. 
10. Statistical Considerations 
10.1 General Principles 
A statistical analysis plan will be developed by the biostatistician and principal investigator based 
on the study protocol, refined and documented prior to the first database lock. Detailed statistical 
analysis methods will also be specified in the statistical analysis plan. 
All statistical analyses will be completed using SAS version 9.4 or above. 
Continuous variables will be described by calculating the total number of cases, missing values, 
mean, standard deviation, median, first quartile, third quartile, minimum, and maximum values. 
Categorical variables are described using frequencies and percentages for each category. If 
required, 95% confidence intervals (95% CI) for frequencies and percentages are calculated. 
10.2 Sample size determination 
This study is an open, single-arm trial with the purpose of bridging Chinese cGVHD patients to 
the US registry study (KD025-213) to assess whether BN101/belumosudil treatment of Chinese versus 
Caucasian cGVHD patients is concordant in terms of efficacy, safety, and PK characteristics, the 
sample size of the trial is not determined by statistical assumptions.  
This study is planned to enroll 30 patients with cGVHD who have undergone at least 1 but not 
more than 5 lines of systemic therapy, and such a sample size is considered to be sufficient to meet the 
needs of assessment with the purpose of bridging. 
10.3 Statistical Analysis Population 
Modified Intent to Treat (mITT): all subjects enrolled and having used at least one dose of study 
drug. 
Per Protocol Set (PPS): The PPS was a subset of the mITT, and included all subjects who have 
used the study drug after enrollment and have had at least 1 post-treatment efficacy assessment, as 
well as no major protocol deviations. The exact definition of a major protocol deviation and the 
inclusion criteria for the PPS were finally determined in the data review meeting. 


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Safety Set (SS): All subjects who had used the study drug after enrollment and had at least 1 
safety assessment. 
Pharmacokinetic analysis Set (PKS): all subjects who have used the study drug since enrollment 
and have post-administration PK data. 
Demographic and baseline characteristics of subjects were statistically analyzed based on mITT. 
mITT was the primary analysis population for the primary efficacy endpoint and PPS was the 
secondary analysis population. Safety analysis based on SS and PK analysis based on PKS. 
10.4 Subgroup Analyses 
Subgroup analyses will be conducted for the following subgroups: 
• 
Severe cGVHD (Yes / No) 
• 
Number of organs involved (<4 / ≥4) 
• 
Number of prior lines of therapy (1 vs. ≥2) 
• 
Duration of cGVHD before enrolment (i.e., from time of cGVHD diagnosis to time of 
enrolment) 
• 
Lung involvement (Yes / No) 
• 
Prior ruxolitinib (Yes / No) 
• 
Prior ibrutinib (Yes / No) 
10.5 Data Analysis 
Database lock and primary analyses are planned to occur approximately 2 to 3 months after the 
last subject is enrolled to complete 6 cycles of study medication. All subjects will continue to be 
followed up for an additional 6 months after the primary analysis as required by the protocol, i.e., the 
study will end 12 months after enrollment of the last subject, and a follow-up analysis will be 
performed at the end of the study. 
10.6 Statistical Analysis Methods 
10.6.1 Distribution of subjects and baseline characterization 
Information on subjects who failed screening was tabulated, with the list including screening 
number and screening failure reason. Screening failure subjects were summarized, including the 
number of screening cases, the number of screening failures, and the percentage of various screening 
failure reasons. 
Demographic information and baseline metrics will be analyzed based on mITT. Descriptive 
statistics will be performed for all demographic information and baseline characteristics (e.g., gender, 
age, ethnicity, height, weight, past medical history, transplantation history, history of GVHD, history 
of treatment for cGVHD, cGVHD severity, etc.) 


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10.6.2 Efficacy Analyses 
10.6.2.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is the ORR, defined as the proportion of subjects evaluated as CR 
or PR according to the NIH Consensus Criteria (2014) at any one post-baseline assessment. Point 
estimates and 95% CIs for ORR will be calculated. The 95% CI for ORR is calculated based on the 
binomial distribution exact probability method. 
ORR is calculated based on mITT and PPS, with mITT as the primary analytic outcome. 
10.6.2.2 Secondary Efficacy Endpoints 
Secondary endpoints are as follows: 
• 
DoR, defined as the time from the first evaluation of CR or PR to the confirmed occurrence 
of cGVHD progression. For subjects who had not experienced cGVHD progression at the 
end of the study, the date of their last objective evaluation was used as the DoR censoring 
date. 
• 
Changes in the Lee Symptom Scale Score: Analyses will include: 
− 
Number of subjects with a ≥7 point reduction 
− 
Number of subjects with a ≥7 point reduction on 2 consecutive assessments 
− 
Duration of a ≥7 point reduction 
• 
Response by organ system: The response assessment for the nine individual organs (Skin, 
Eyes, Mouth, Esophagus, Upper GI, Lower GI, Liver, Lungs, and Joints and fascia). 
• 
Number and percentage of subjects who have a best response of PR and number and 
percentage of subjects who have a best response of CR. 
• 
Change in corticosteroid dose 
− 
The prednisone equivalent dose of corticosteroids (mg/kg/day) during the study will be 
analyzed. 
• 
Change in calcineurin inhibitor dose. 
• 
FFS, FFS is defined as the absence of cGVHD treatment change, non-relapse mortality and 
recurrent malignancy. Median FFS (from first dose of BN101/Belumosudil) and landmark 
FFS at 1 year(if applicable) will be analyzed. 
• 
OS, defined as time from first dose of BN101/belumosudil to the date of death due to any 
cause. 
• 
Changes in cGVHD global severity rating using the Clinician-Reported Global cGVHD 
Activity Assessment 
• 
Changes in symptom activity using the cGVHD Activity Assessment Patient Self-Report 


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Descriptive statistics will be provided for all secondary endpoints. 
For DoR (only for subjects determined to have CR and/or PR), FFS, and OS, the median, first 
quartile, third quartile, and their two-sided 95% CIs were calculated using the Kaplan-Meier method, 
and survival curves were plotted. 
10.6.2.3 Exploratory efficacy endpoints 
Descriptive statistics of changes in PROMIS Physical Mental Functioning Global Health Score. 
10.6.3 Safety Analyses 
Treatment exposure will be summarized. 
For vital signs (including temperature, respiratory rate, sitting blood pressure, and pulse), and 
physical examination, describe post-treatment changes relative to baseline. 
Descriptive statistics of laboratory test abnormalities will be indexed and presented in a cross-
tabular format to show the change in laboratory test results of severity ≥3 (per NCI CTCAE v5.0) 
pre- and post-treatment with study medications. 
For 12-lead ECGs, changes in mean and maximum QTcB and QTcF values relative to baseline 
will be calculated. 
Each type of AE occurring during the study was coded using MedDRA (version 20.1 or above), 
frequency summarized according to system organ classification, preferred terminology, and frequency 
summarized and tabulated for AEs of different severity according to the highest level of severity 
(grades 1-5 according to NCI CTCAE v5.0) and relevance to the study drug. Count the number of 
subjects who experienced each type of AE, regardless of the number of AEs reported per 
subject.Descriptively summarize AEs, SAEs, AEs of severity ≥ grade 3 (according to NCI CTCAE 
v5.0), AEs leading to withdrawal from the study, AEs leading to discontinuation of study treatment, 
AEs leading to dose adjustments of the study medication, and correlation with the study medication 
for each of the above types of AEs/SAEs. List of subjects with each type of AE/SAE and death. 
10.6.4 Pharmacokinetic Analyses 
Individual drug-time profiles of BN101/belumosudil and its metabolites (m1 and m2) were 
plotted for each subject, and average drug-time profiles of BN101/belumosudil and its metabolites (m1 
and m2) were plotted. 
PK parameters of BN101/belumosudil and its metabolites (m1 and m2) were analyzed.PK 
parameters included, but were not limited to Cmax, Tmax, T1/2, AUC0-t, AUCinf, CLz/F, Vz/F, Kel, Cmin,ss, 
Cmax,ss, Cav,ss, RAUC1, RAUC2, RCmax. If metabolites m1 and m2 of BN101/belumosudil can be detected 
and identified, the ratios of molecular weight-adjusted metabolites (m1 and m2) to the prodrug (P) 
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include, but are not limited to, number of cases, arithmetic mean, standard deviation, coefficient of 
variation, median, first quartile, third quartile, minimum and maximum values. 
PK analysis methods will be presented in a separate PK analysis plan. 
10.7 Interim Analysis 
No interim analysis is planned for this study. 
11. Clinical Trial Management 
11.1 Statement 
This clinical trial will be conducted in accordance with the sponsor's and CRO's standard 
operating procedures, which are designed to ensure that the trial adheres to the Declaration of Helsinki 
(2013 version), Guidelines for Good Clinical Practice issued by the ICH[24], Guidelines for Good 
Clinical Practice issued by the NMPA[25] and the requirements of drug clinical trial regulations were 
implemented. 
By signing the protocol, the investigator agrees to follow the instructions and procedures set forth 
in the protocol and to follow the principles of GCP to which this protocol conforms, as well as all local 
regulations and principles of medical research used. 
11.2 Ethical Aspects 
The study was designed and prepared on the basis of the Declaration of Helsinki of the World 
Medical Association, taking into account the rights and welfare of patients. Patients who voluntarily 
agree to participate in a clinical trial and sign the ICF will only become subjects if the clinical trial 
principal investigator or investigator explains the purpose of the trial and all potential possibilities to 
the patient. 
Clinical trial investigators and investigators participating in the trial should properly understand 
and be familiar with the study plan and be able to take preparatory measures in advance, such as 
countermeasures in the event of unanticipated adverse events, required reports, and adequate training. 
Clinical investigators must comply with the Declaration of Helsinki (2013 version), Guidelines for 
Good Clinical Practice[24] issued by the ICH, and Good Clinical Practice (GCP) [25]issued by the NMPA, 
as well as relevant regulations, when conducting clinical trial studies. 
The principal investigator and the personnel involved in the study should comply with the 
contents specified on the trial protocol and scientifically conduct the trial with the currently recognized 
level of technology. 
In accordance with national policies and regulations, the investigator is required to provide the 
EC with trial-related documentation. 
A copy of the EC approval and a list of the documents reviewed must be submitted to the sponsor 


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before the drug is shipped to the investigator.The EC approval document must be accompanied by a 
list of all committee members involved in the discussion of the approval document and their respective 
responsibilities. 
When the EC approves this study protocol, the sponsor is required to register on the Drug Clinical 
Trial Registration and Information Publication Platform. 
Before the clinical trial starts, it must be approved by the EC and the pharmacovigilance 
administration. 
Modifications to the study protocol need to be submitted to the EC for approval and 
communicated to the health authorities according to local requirements. 
During the course of the clinical study, the investigator must inform the EC of any SAE related 
to the safety of the clinical study that may affect the safety of the subjects and the conduct of the trial. 
The EC should be informed of the end of the study. 
11.3 Original Data Verification 
The investigator must handle all data obtained in the course of the clinical study appropriately to 
ensure the rights and privacy of the subjects participating in the clinical study. The investigator must 
consent to the access and review of clinical study data by the monitor/auditor/inspector as required to 
verify the accuracy of the original data and to understand the progress of the study. If validation of the 
original 
records 
is 
not 
possible, 
the 
investigator 
should 
agree 
to 
assist 
the 
Supervisor/Auditor/Inspection in further validation of the quality control of the data. 
11.4 Quality Assurance and Audit 
All drugs and materials applied in all clinical studies must be subject to quality control. The 
sponsor and its authorized personnel or the relevant healthcare governing body have the right to audit 
the clinical study, the purpose of which is to ensure the authenticity of the data recorded in the clinical 
study as well as to comply with the provisions of the clinical study protocol. 
The study will be organized, conducted and reported in accordance with the standard operating 
procedures of the protocol, the sponsor and the CRO. Quality Assurance (QA) is defined in ICH E6 as 
"a planned systematic action to ensure that the conduct of a trial and the generation, recording, and 
reporting of data are in accordance with GCP and applicable regulatory requirements". Sponsor QA 
will be performed in accordance with the provisions of the Study Audit Plan.ICH E6 Section 5.19.3(b) 
states that the development of the Audit Plan and the Trial Audit Process should be guided by the 
significance of the trial in the filing with the competent authority, the number of subjects in the trial, 
the type and complexity of the trial, the level of risk posed to the trial subjects, and any identified 
issues.QA Work can be outsourced to a CRO or independent consultant. The investigator is required 
to support the audit by attending the audit as requested by the auditor and allowing the auditor to have 


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direct access to the raw data/documentation, including all medical records, study-related documents 
and correspondence, and informed consent documents for the clinical trial. Subjects in clinical studies 
will be informed of the process of clinical study review, but subject privacy and data information will 
be strictly protected. 
11.5 Informed Consent Form 
It is the responsibility of the investigator to explain to each subject the purpose, methodology, 
benefits and potential risks of this clinical trial, alternative treatments available, and the rights and 
obligations of the subject in accordance with the Declaration of Helsinki; subjects should be made 
aware that they have the right to withdraw from this trial at any time and that their personal interests 
will not be jeopardized. An ICF signed by the subject must be obtained prior to any operational 
procedure related to the clinical trial. 
A verbal explanation must be given when giving written informed consent to the subject. 
Informed consent must be dated and signed by each subject or his/her legal guardian or representative. 
One copy of the signed ICF (including the information page) will be kept by the subject and the other 
copy will be retained by the clinical center for retention in the study file. 
The ICF must be agreed to and signed by the subject before any study-related process begins. 
Prior to obtaining informed consent, the investigator or his/her designee should provide the subject 
with sufficient time and opportunity to inquire about the details of the trial and to decide whether to 
participate in the trial. The informed consent process needs to be documented in the medical record on 
the day of the screening visit. 
The investigator is responsible for the informed consent process. If any information is obtained 
during the trial that is relevant to the subject's willingness to continue participation in this trial, the ICF 
must be updated and given to the subject to confirm the subject's willingness to continue participation. 
The revised ICF requires ethical approval before it is given to the subject. 
By signing the informed consent, the subject/patient must also agree to allow the sponsor's 
authorized clinical trial monitor, drug regulatory authority, to access the raw data obtained about the 
clinical study, and the accessor must abide by the confidentiality statement. 
11.6 Protocol Amendment 
If there are any major changes in the implementation of the protocol after approval by the EC, the 
principal investigator of the responsible unit shall write and sign a "Statement of Protocol Amendment". 
At the same time, it must be reported to the EC for approval before implementation. 
For non-substantial modifications, the principal investigator of the clinical center， the 
statistician, and the sponsor should discuss and decide on the modifications together and inform the 


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other participating centers. The investigator shall not implement any protocol deviation or change 
without the consent of the sponsor and prior review and written approval by the EC (ICH E6 4.5.2). 
Any changes to the protocol, whether significant or non-significant, are required to be in writing. 
Substantial protocol revisions that clearly affect the safety of subjects, the scope of the study, or the 
scientific quality of this study require approval from all study clinical center ECs. In order to protect 
the safety of all subjects in the study, the above requirements shall not prevent the investigator or 
sponsor from taking any emergency measures. If the investigator believes that immediate protocol 
changes are necessary for safety reasons, the investigator must promptly notify the sponsor's 
Designated Authority and notify the Clinical Center EC in accordance with the policies established by 
the EC approving the study, and with local regulations and policies. Changes affecting only aspects of 
the administration of the study do not require substantive protocol revisions or EC approval; however, 
the EC must be notified of these changes. 
11.7 Protocol deviation 
The investigator is required to perform this clinical trial in accordance with the EC approved 
clinical trial protocol and in compliance with GCP regulations. The protocol has been developed to 
enable the investigator to follow the provisions of ICH E6 Section 4. During the course of the trial, the 
investigator should not deviate from the protocol unless emergency measures are taken to eliminate 
immediate harm to subjects. When other unintended circumstances occur that require deviation from 
the procedures specified in the protocol, the investigator should consult with the Medical Monitor (and 
IRB or EC, as necessary) to determine the appropriate measures to take. 
The clinical center shall document all protocol deviations in the subject's original data, including, 
but not limited to, the time of occurrence of the protocol deviation, the time of discovery, a description 
of the event, and the measures taken. In the event of a serious protocol deviation, the clinical center 
shall promptly notify the medical monitor, clinical monitor, IRB and EC. 
11.8 Case Report Form 
The CRO database programmer will create an eCRF in the EDC system. eCRFs identify different 
subjects on the eCRF only by appropriate identification codes (e.g., study clinical center number and 
subject number) and initials. eCRFs are used to record clinical study information about subjects and 
are an integral part of the study and related research reports, so data entry must be accurate and 
complete. eCRFs are entered in the EDC system by the investigator or a staff member authorized by 
Investigator (to be noted on the Study Authorization Form) to make entries in the EDC system. All 
data entry must be ensured to be completed and stored. The investigator must declare, through an 
electronic signature, that all information in the eCRF is true. 
In clinical studies, completion of the eCRF is usually required as soon as possible after each visit 


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to document the subject's condition. 
Medical history records and other records related to the subject's disease progression during the 
course of the study are maintained by the investigator. These records should contain the following: 
original or copies of laboratory data and results of other medical tests (e.g., electrocardiograms, etc.), 
which must be kept at the clinical center along with the subject's medical history. 
11.9 Monitor 
The sponsor commissions the CRO to conduct the monitoring work. 
Prior to the selection of a clinical center to participate in the study, a center selection visit will be 
conducted to confirm that the center, instrumentation, and staff meet the protocol requirements and 
GCP. 
During the course of the study, the CRO conducts on-site inspections of the clinical centers 
according to the inspection plan and completes an inspection report for each inspection. 
The activities of the monitor for study monitoring include: 
 
Clinical center study initiation visit to collect and distribute necessary pre-study required 
documents; give guidance instructions to the investigator and his/her clinical staff regarding 
the protocol, study process, and expectations; obtain assurances that the investigator will 
conduct the trial in accordance with the study requirements and the GCP, and present the 
study materials to the investigator and the appropriate study staff. 
 
Monitor Visit: In accordance with GCP requirements, the monitor involved in the current 
study is fully aware of the issues related to confidentiality and compares the data in the eCRF 
with the data in the hospital or clinical records (source material). Prior to the start of the 
study, the monitor should discuss with the investigator the specific items required as source 
material, determine the nature and location of all source material to ensure that the sponsor 
or investigator is aware of the source of the raw data used to complete the eCRF, and that 
the sponsor authorizes the monitor's authority for checking and verifying; all observations 
and findings made during the monitoring process must be verifiable. If the electronic records 
are kept at the clinical center, the method of checking must be discussed with the study 
member. 
The original information must be available at a minimum to confirm: 
- 
Subject identity, eligibility and participation in the trial; 
- 
Proper informed consent procedures; 
- 
The date of the visit; 
- 
Documentation of safety and efficacy parameters; 
- 
AE adequate reporting and visits; 


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- 
Treatment of concomitant medications; 
- 
Records of receipt/dispensing/return of medications; 
- 
Study drug administration information; 
- 
Subject completion of treatment, termination of treatment, or withdrawal from the study, 
and appropriate reasons; 
- 
Data are true, accurate, and complete; 
- 
Subject safety and rights are protected; 
- 
The investigator conducts compliance with the currently approved protocol, GCP and 
all relevant regulatory requirements. 
The objectives that need to be achieved by surveillance include: 
 
Checking and evaluating the progress of the study; 
 
Reviewing the clinical data collected; 
 
Implement a source document verification process; 
 
Identify any problems and develop solutions. 
During the course of the study, the monitor will need to have direct access to all relevant 
documents with the consent of the investigator, who will ensure that he or she and relevant clinical 
staffs meet with the monitor on a regular basis to discuss the findings of the visit and any relevant 
issues. 
11.10 Intellectual Property 
All information obtained from the sponsor is the intellectual property of the company, and as such 
must be kept strictly confidential by the clinical trial investigator and all others involved, and must not 
be divulged to third parties without the prior consent of the sponsor. 
11.11 Subject Privacy 
Investigators must ensure that the privacy of clinical trial subjects is protected. Clinical trial 
subjects may be identified in all documentation submitted to the sponsor only by their clinical trial 
subject number and initials, and not by the subject's name. The investigator must maintain proper 
custody of the name and address of the subject of the clinical trial in question and the identification 
code sheet that corresponds to the subject number. The subject identification code list is to be 
maintained by the Investigator in strict confidence and is not to be passed on to the Sponsor. 
12. Paper Publication 
The sponsor has exclusive rights to this study. The authors and manuscript will reflect the 
collaboration between multiple investigators and the staff of the clinical center and the sponsor, and 
the order of authorship will be established according to the scientific contribution of the investigators 


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to the protocol and the number of subjects enrolled. In principle, the scientific contribution of the 
investigators to the protocol will be the primary criterion, and the number of active cases enrolled will 
be the secondary criterion, and the above criteria will be used to determine the first author, the 
corresponding author, and the author rank order prior to writing the manuscript. Because there are 
many research centers participating in this study, individual centers or individual investigators will not 
be allowed to write articles for publication until the final report of the multicenter study has been 
completed, except with the consent of the sponsor. The final decision on manuscript and publication 
rests with the sponsor. 
13. Study Documentation, CRFS, and Recod Keeping 
13.1 Origional documents 
In the trial, original information is defined as the following： 
 Records related to the ICF, including instructions for subjects; 
 Medical records, etc. as the basis for completing the eCRF; 
 Records of the use of study medications; 
 subject diary cards. 
13.2 Document retention at Clinical center 
13.2.1 Documents relating to ethics committees 
The person responsible for data retention in the clinical center must retain EC meeting minutes 
and summaries until 5 years after the trial drug is approved for marketing. If the sponsor wishes to 
retain them for a longer period of time, the parties will discuss and decide on the duration and method 
of retention. The person responsible for data retention or the investigator will need to contact the 
sponsor if the trial unit makes any changes to document retention. 
13.2.2 Documents relating to study 
The person responsible for data retention at the clinical center must retain the following 
documents until 5 years after the trial drug has been approved for marketing. If the sponsor wishes to 
retain them for a longer period of time, the parties will discuss and decide on the duration and method 
of retention. The person responsible for data retention or the investigator will need to liaise with the 
sponsor if the trial unit makes any changes to document retention. 
 Original documents; 
 Originals or copies of trial contracts, ICFs, and other GCP-related documents provided by 
study clinical center staff; 
 Trial protocol, GCP-related documents obtained from the EC, or other GCP-related 
documents obtained; 


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 Records of the administration of the medication used in the trial, and other records relevant to 
the conduct of the trial. 
13.3 Retention of documents on sponsors 
The sponsor will keep the following information (including documents and data) until 5 years 
after the approval of the test drug for marketing. Longer retention periods may be required in 
accordance with relevant regulations. It is the responsibility of the sponsor to inform the 
investigator/clinical center when this information is no longer required to be retained. 
 Original or copy of the trial protocol, trial contract, study report, or GCP-related information 
provided by the sponsor; 
 Case report forms, GCP-related notifications, or GCP-related information obtained from the 
investigator; 
 Monitoring, audit-related records, or other relevant operational records; 
 Data obtained during the trial; 
 Relevant records required by GCP. 
 
 


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14. References 
[1] Yu Zhang(Review), Qifa Liu(Reviewer). Clinical manifestations and diagnosis of chronic graft-
versus-host disease. International Journal of Blood Transfusion and Hematology, 2010;33(4):315-
318. 
[2] Lee SJ. Classification systems for chronic graft-versus-host disease. Blood. 2017; 129(1):30-37 
[3] Arai S, Arora M, Wang T, et al. Increasing incidence of chronic graft-versus-host disease in 
allogeneic transplantation: a report from the Center for International Blood and Marrow 
Transplant Research. Biol Blood Marrow Transplant. 2015;21(2):266-274 
[4] Arora M, Cutler CS, Jagasia MH, et al. Late acute and chronic graft-versus-host disease after 
allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(3):449-
455. 
[5] Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015; 125(4): 
606-615 
[6] Garnett C et al. Treatment and management of graft-versus-host disease: improving response and 
survival. Ther Adv Hematol 2013;46(6):366-378  
[7] Ibrutinib Prescribing Information 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205552s020lbl.pdf accessed 28-
Mar, 2018 
[8] Miklos D et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 
2017;130(21):2243-2250 
[9] Leung T, Manser E, Tan L, Lim L. A novel serine/threonine kinase binding the Rasrelated RhoA 
GTPase which translocates the kinase to peripheral membranes. J Biol Chem. 
1995;270(49):29051-4. 
[10] 2 Nakagawa O, Fujisawa K, Ishizaki T, Saito Y, Nakao K, Narumiya S. ROCK-I and ROCK-II, 
two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice. 
FEBS Lett. 1996;392(2):189-93. 
[11] 3 Herskowitz JH, Feng Y, Mattheyses AL, Hales CM, Higginbotham LA, Duong DM, et al. 
Pharmacologic inhibition of ROCK2 suppresses amyloid-beta production in an Alzheimer's 
disease mouse model. J Neurosci. 2013;33(49):19086-98. 
[12] 4 Noguchi M, Hosoda K, Fujikura J, Fujimoto M, Iwakura H, Tomita T, et al. Genetic and 
pharmacological inhibition of Rho-associated kinase II enhances adipogenesis. J Biol Chem. 
2007;282(40):29574-83. 
[13] 5 Shi J, Surma M, Zhang L, Wei L. Dissecting the roles of ROCK isoforms in stressinduced cell 
detachment. Cell Cycle. 2013;12(10):1492-500. 
[14] 6 Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, Chen W, Scher JU, Mo R, et al. Selective oral 
ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-
dependent mechanism. Proc Natl Acad Sci U S A. 2014;111(47):16814-9. 
[15] 7 Zhou Y, Huang X, Hecker L, Kurundkar D, Kurundkar A, Liu H, et al. Inhibition of 
mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis. J 
Clin Invest. 2013;123(3):1096-108. 
[16] 8 Tybulewicz VL, Henderson RB. Rho family GTPases and their regulators in lymphocytes. Nat 
Rev Immunol. 2009;9(9):630-44. 


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[17] 9 Biswas PS, Gupta S, Chang E, Song L, Stirzaker RA, Liao JK, et al. Phosphorylation of IRF4 
by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice. 
J Clin Invest. 2010;120(9):3280-95. 
[18] 10 Isgro J, Gupta S, Jacek E, Pavri T, Duculan R, Kim M, et al. Enhanced rho-associated protein 
kinase activation in patients with systemic lupus erythematosus. Arthritis Rheum. 
2013;65(6):1592-602. 
[19] Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 
2008;133(5):775-87. 
[20] National Pharmacopoeia Commission. Guidelines for Validation of Methods for Quantitative 
Analysis of Biological Samples in Part 9012 of the Chinese Pharmacopoeia. 2015. 
[21] ATS/ERS Task Force: Standardisation of Lung Function Testing; Standardization of Spirometry. 
Eur Respir J 2005; 26: 319–338. 
[22] JP Zheng, XL Liang. "Interpretation and debates on the standardized pulmonary function report 
recommended by the American Thoracic Society". Chinese Journal of Evidence-Based Medicine, 
2018;18(3):1-5. 
[23] Jian W, Gao Y, Hao C, et al. Reference values for spirometry in Chinese aged 4–80 years. J Thorac 
Dis, 2017;9(11):4538-4549. 
[24] ICH. Guidelines for Good Clinical Practice E6(R1). 1996. 
[25] NMPA. Good Clinical Practice. 2003. 
 
 


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15. Appendix 
Appendix 1 Schedule of Assessments 
Cycle Day（d） 
 
Assessment 
Screening/Baseline 
Cycle 1 
Cycle 2~N13,14 End of Treatment 
(EOT)15 
28-Day 
Follow-Up 16 
Long Term  
Follow-Up 17 
-14 ~ -1 
-7 ~ -1 
C1D1 
C1D8、15 
(±3) 
CxD1 
(±3) 
(+7) 
(±7)  
At the end of 
treatment or at the 
end of the main 
study 
Written Informed Consent 1 
X 
 
 
 
 
 
 
 
Subject Demography  
X 
 
 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
 
 
Transplant History 
X 
 
 
 
 
 
 
 
GVHD History 
X 
 
 
 
 
 
 
 
cGVHD Prior Treatments 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
cGVHD severity assessment 
 
X 
 
 
 
 
 
 
Efficacy Assessments 
 
 
 
 
 
 
 
 
Clinician-reported global cGVHD 
activity assessment 
 
X 
 
 
X 
X 
 
 
Response Assessment 2 
 
 
 
 
X 2 
X 
 
 
Pulmonary Function Tests 2,3 
 
X 
 
 
X 2,3 
X 
 
 
Patient-reported cGVHD acticity 
assessment2 
 
X 
 
 
X 2 
X 
 
 
Lee Symptom Scale Score 2 
 
X 
 
 
X 2 
X 
 
 
PROMIS Global Health Score 2 
 
X 
 
 
X 2 
X 
 
 
Document Corticosteroid Dosage 
Corticosteroid Dosage to be collected from the date the ICF is signed until 28 days after last dose of 
study drug. 
 
Document other cGVHD therapies 
cGVHD therapies to be collected from the date the ICF is signed until 28 days after last dose of study 
drug. 
 
Safety Assessments 
 
 
 
 
 
 
 
 
Complete PE 4 
X 
 
 
 
 
 
 
 
Symptom directed PE 
 
 
X 
X 
X 
X 
X 
 
Vital signs 5 
X 
 
X 
X 
X 
X 
X 
 


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Cycle Day（d） 
 
Assessment 
Screening/Baseline 
Cycle 1 
Cycle 2~N13,14 End of Treatment 
(EOT)15 
28-Day 
Follow-Up 16 
Long Term  
Follow-Up 17 
-14 ~ -1 
-7 ~ -1 
C1D1 
C1D8、15 
(±3) 
CxD1 
(±3) 
(+7) 
(±7)  
At the end of 
treatment or at the 
end of the main 
study 
Weight 
X 
 
X 
X 
X 
X 
X 
 
ECOG PS score 
X 
 
X 
 
X 
X 
X 
 
Hematology 6 
 
X 
X 
X 
X 
X 
X 
 
Urinalysis 7 
 
X 
X 
 
X 
X 
X 
 
Clinical Chemistry 8 
 
X 
X 
X 
X 
X 
X 
 
Virology 9 
X 
 
 
 
 
 
 
 
12-Lead ECG 10 
X 
 
X 
 
X 
X 
X 
 
Ultrasonic cardiogram（LVEF） 
X 
 
X18 
X 
X 
 
Pregnancy test 11 
 
X 
X 
 
X 
X 
X 
 
Concomitant medications /procedures 
X 
 
X 
X 
X 
X 
X 
 
Adverse events 
X 
 
X 
X 
X 
X 
X 
 
Long term follow-up 
 
 
 
 
 
 
 
X 
Investigational Product 
 
 
 
 
 
 
 
 
Study Drug administration 12 
 
 
X 
X 
X 
 
 
 
Dispense/Collect Study Drug & 
Study Drug Diary 
 
 
X 
X19 
X 
X 
 
 
Pharmacokinetics 
See PK Table 
cGVHD = chronic graft versus host disease；d = day；ECOG = Eastern Cooperative Oncology Group；GVHD = graft versus host disease；LVEF = left 
ventricular ejection fraction；PROMIS = Patient-Reported Outcomes Measurement Information System；PS = Performance Status 
1. 
The informed consent form must be signed before any study procedures begin. 
2. 
To be assessed on Day 1 of Cycles 2-5 and then on Day 1 of every other Cycle thereafter (i.e. Day 1 of Cycles 2, 3, 4, 5, 7, 9, 11 etc.) 
3. 
Lung function assessment to be conducted at time of response assessments (see item 2). Pulmonary Function Tests (PFTs), to include FEV 1 , FVC, DL CO 
(corrected for Hb), TLC, and RV, will be performed at screening/baseline and Day 1 of Cycles 4, 7, 13，every 6 th Cycle thereafter and EOT. On Day 1 of other 
cycles with response assessments, spirometry (FEV 1 and FVC) is sufficient. 
4. 
Assessment by organ and system. A comprehensive physical examination includes: height, general condition, head and neck, lymph nodes, skin, chest, abdomen, 
musculoskeletal system (including limbs and spine), and nervous system. 
5. 
Vital sign includes temperature, respiratory rate, pulse/heart rate, blood pressure. Sitting blood pressure and heart rate to be obtained after 5 minutes of rest. 
6. 
Hematology：hemoglobin (Hb), hematocrit (HCT), Red blood cell count (RBC), white blood cell count (WBC), white blood cell classification count (including 
neutrophils, lymphocytes, monocytes, basophils, eosinophils), platelets (PLT). If it is done within 3 days prior to C1D1, it does not need to be repeated on C1D1. 


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Cycle Day（d） 
 
Assessment 
Screening/Baseline 
Cycle 1 
Cycle 2~N13,14 End of Treatment 
(EOT)15 
28-Day 
Follow-Up 16 
Long Term  
Follow-Up 17 
-14 ~ -1 
-7 ~ -1 
C1D1 
C1D8、15 
(±3) 
CxD1 
(±3) 
(+7) 
(±7)  
At the end of 
treatment or at the 
end of the main 
study 
7. 
Urinalysis：pH、urine protein (U-PRO), urine white blood cells (U-WBC), urine red blood cells (U-RBC), urine sugar (U-GLU), urine occult blood, urobilirubin, 
urine bilirubin, urine nitrite and urine ketone bodies (U-KET). If it is done within 3 days prior to C1D1, it does not need to be repeated on C1D1. 
8. 
Clinical chemistry：aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), γ-
glutamyltransferase (γ-GGT), total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB), total protein (TP); Creatinine (sCr), Urea (Urea) or urea nitrogen 
(BUN), uric acid (UA), potassium (K), sodium (Na), chlorine (Cl), calcium (Ca), phosphorus (P), magnesium (Mg), blood glucose (GLU). If it is done within 3 
days prior to C1D1, it does not need to be repeated on C1D1. 
9. 
Virology includes Hepatitis B Surface antigen (HBsAg), Hepatitis B Surface Antibody (HBsAb), Hepatitis B core antibody (HBcAb), Hepatitis Be antigen 
(HBeAg), Hepatitis Be antibody (HBeAb), Hepatitis C antibody (HCV-Ab), human immunodeficiency virus (HIV) antibody, Hepatitis B virus DNA (HBV-DNA) 
(if applicable), Hepatitis C virus RNA (HCV-RNA) (if applicable). If they are done at the site within 28 days prior to screening and reports can be provided, the 
investigator determines that the test can be used as a result of the screening period. When HBcAb or HCV-Ab is positive, HBV-DNA or HCV-RNA should be 
tested to rule out active infection. 
10. 12-Lead ECG – see ECG Assessment table. 
11. Female of childbearing age are tested for pregnancy. For this study, the reproductive age was defined as non-menopausal, and menopause included natural 
amenorrhea ≥12 months; Or natural amenorrhea ≥24 months after chemotherapy; Or natural amenorrhea ≥6 months and serum follicle-stimulating hormone (FSH) 
level > 40 IU/L; Or confirmed surgical records and/or pathology reports confirmed after bilateral oophorectomy. Serum pregnancy tests for women of childbearing 
age during the screening period must be negative. Urine pregnancy test can be performed as needed during the study treatment. Positive results are to be confirmed 
with serum testing. If the urine pregnancy result is positive, subjects should stop the study drug treatment and withdraw from the study, and the investigators will 
continue to follow up subjects until delivery and 30 days after delivery. Subjects who did not deliver were followed up until the end of the pregnancy. 
12. On Day 1 of Cycles 1 to 7, subjects will take their dose at the clinic and then will be dispensed study drug for home administration. Instruct subjects to fill in the 
study drug dairy. From Cycle 8 onwards, the Day 1 dose may be taken at home or in the clinic. 
13. The end of the main study is defined as 12 months after the last subject was enrolled.Subjects who have not yet experienced cGVHD progression at the end of the 
main study, and in the judgment of the investigator, the benefits of continued dosing outweigh the risks, may submit a written request and, upon approval by the 
sponsor's Medical Director and documentation of the subject's willingness to continue the treatment, the sponsor will continue to provide BN101/belumosudil 
medication at no cost until cGVHD progression, intolerable toxicity, initiation of a new cGVHD therapy, recurrence of hematological neoplasm, loss to follow-
up, withdrawal of consent, or death, etc., whichever occurred first.For subjects assessed as "Lack of Response - Mixed" and "Lack of Response - Progression"(see 
the main body of the protocol), if the investigator believed that these subjects could continue to benefit from treatment with BN101/belumosudil, the treatment 
may be continued after a written application was submitted, and approval from the Sponsor's Medical Director as well as documentation of the subject's willingness 
to continue treatment was obtained. 
14. On the first day of cycle 7 (C7D1) and all subsequent odd cycles (C7D1, C9D1, C11D1, etc.), subjects will receive 2 cycles of study drugs and 2 copies of drug 
dairy and return to the clinic for efficacy and safety assessment every other treatment cycle, as well as dispense/collect study drugs until the end of the main study. 
15. Subjects will return to the clinic for EOT assessment within 7 days after the final administration of the study drug or at the end of the main study (only for subjects 
who have not discontinued the study drug at the end of the main study). Subjects who withdraw from the trial early should also return to the clinic for EOT 
assessment. End-of-treatment visits are also required at the end of the main study if subjects have not discontinued study drug at the end of the main study. EOT 


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Cycle Day（d） 
 
Assessment 
Screening/Baseline 
Cycle 1 
Cycle 2~N13,14 End of Treatment 
(EOT)15 
28-Day 
Follow-Up 16 
Long Term  
Follow-Up 17 
-14 ~ -1 
-7 ~ -1 
C1D1 
C1D8、15 
(±3) 
CxD1 
(±3) 
(+7) 
(±7)  
At the end of 
treatment or at the 
end of the main 
study 
visits should be done prior to new treatment. 
16. Subjects will receive the assessment at 28 days (±7 days) after the last study drug administration. If subjects started a new cGVHD treatment within 28 days of 
the last study drug administration, this visit needs to be completed before receiving the new treatment. 
17. Subjects who discontinue study therapy during the main study period will be contacted by phone approximately every 12 weeks to confirm survival, any changes 
in cGVHD therapy, and any antitumor therapy until the end of the main study period. 
18. Subjects who have not yet experienced cGVHD progression at the end of the main study, and in the judgment of the investigator, the benefits of continued dosing 
outweigh the risks, may submit a written request and, upon approval by the sponsor's Medical Director and documentation of the subject's willingness to continue 
the treatment, the sponsor will continue to provide BN101/belumosudil medication at no cost until cGVHD progression, intolerable toxicity, initiation of a new 
cGVHD therapy, recurrence of hematological neoplasm, loss to follow-up, withdrawal of consent, or death, etc., whichever occurred first. During this time, the 
study will continue to collect participants' serious adverse events (SAEs) (up to 28±7 days after the last dose or start new cGVHD therapy), study drug use, and 
survival (or can be contacted by telephone). 
19. During the treatment, it will be up to the investigator to decide whether to perform an echocardiogram according to the subject's condition. 
20. C1D8 and C1D15 do not need to dispense/collect study drugs, only dispense/collect study drug diary. 
 
 
 
 


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Appendix 2 Pharmacokinetics Sampling 
PK Sample Collection 
Sample 
Blood (approximately 3 mL every time point)，separated plasma 
Extensive blood sampling: 12 subjects at selected sites 
Cycle 1 
Day 1 
Prior to BN101/belumosudil dosing, and at 1、1.5、2、3、4、
6、8、12 hours post dose  
Day 2 
Prior to BN101/belumosudil dosing 
Day 15 
Prior to BN101/belumosudil dosing 
Cycle 2 (or when withdrawing 
from the study early) 
Day 1 
Prior to BN101/belumosudil dosing，and at 1、1.5、2、3、
4、6、8、12 hours post dose 
Day 2 
Prior to BN101/belumosudil dosing 
Cycle 3 (or when withdrawing 
from the study early) 
Day 1 
Prior to BN101/belumosudil dosing 
Sparse PK: All Subjects 
Cycle 2 (or when withdrawing 
from the study early, except for 
those who were in the extensive 
blood sampling group) 
Day 1 
Prior to BN101/belumosudil dosing，and at 1.5、4 hours post 
dose 
Cycle 4 (or when withdrawing 
from the study early) 
Day 1 
Prior to BN101/belumosudil dosing，and at 1.5、4 hours post 
dose 
 
 
 


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Appendix 3 Pharmacokinetic Blood Sample Collection Time Window 
PK Time point 
Time Window 
Extensive blood sampling 
Sparse blood sampling 
Prior to BN101/belumosudil 
-60 minutes to BN101/belumosudil 
dose 
-60 minutes to BN101/belumosudil 
dose 
1、1.5、2、3 hours post dose 
± 10 minutes 
± 10 minutes 
4、6、8 hours post dose 
± 15 minutes 
NA 
12 hours post dose 
± 60 minutes 
NA 
Note：NA = not applicable 
 
 


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Appendix 4 ECG Assessments 
ECG Assessments 
Cycle 1 
Day 1 
Triplicate 
ECG 
within 
60 
minutes 
prior 
to 
BN101/belumosudil dosing and at 1.5 hours post dose (± 20 
minutes), they should be taken at 1-2 minutes intervals 
Cycle 2 
Day 1 
Triplicate 
ECG 
within 
60 
minutes 
prior 
to 
BN101/belumosudil dosing and at 1.5 hours post dose (± 20 
minutes), they should be taken at 1-2 minutes intervals 
Cycle 4 
Day 1 
Triplicate 
ECG 
within 
60 
minutes 
prior 
to 
BN101/belumosudil dosing and at 1.5 hours post dose (± 20 
minutes), they should be taken at 1-2 minutes intervals 
Cycle 7 and every 2 cycles 
thereafter (only until the end of the 
main study) 
Day 1 
Single ECG at 1.5 hours post dose (± 20 minutes) 
EOT 
 
Single ECG 
28-Day Follow-up (only until the 
end of the main study) 
 
Single ECG 
 
 
 


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Appendix 5  cGVHD Activity Assessment for Clinician 
 
Score 0 
Score 1 
Score 2 
Score 3 
Esophagus 
No 
esophageal 
symptoms 
Occasional dysphagia or 
odynophagia with solid 
food or pills during the 
past week 
Intermittent dysphagia or 
odynophagia with solid and 
pills, but not for liquids or 
soft foods, during the past 
week 
Dysphagia 
or 
odynophagia 
for 
almost 
□ 
□ 
□ 
□ 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
 
Score 0 
Score 1 
Score 2 
Score 3 
Upper GI 
No symptoms 
Mild, occasional 
symptoms, with little 
reduction in oral intake 
during the past week 
Moderate, intermittent 
symptoms, with some 
reduction in oral intake 
during the past week 
More severe or 
persistent symptoms 
throughout the day, 
with 
marked 
reduction 
in oral intake, on 
almost 
every day of the past 
week 
□ 
□ 
□ 
□ 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
 
Score 0 
Score 1 
Score 2 
Score 3 
Lower GI 
No loose or 
liquid stools 
during the past 
week 
Occasional loose or 
liquid stools, on some 
days during the past 
week 
Intermittent loose or 
liquid stools throughout 
the day, on almost every 
day of the past week, 
without requiring 
intervention to prevent or 
Voluminous 
diarrhea on almost 
every day of the 
past week, requiring 
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correct volume depletion 
volume depletion 
□ 
□ 
□ 
□ 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
 
Score 0 
Score 1 
Score 2 
Score 3 
Lungs 
No symptoms 
Mild symptoms 
(shortness of breath 
after climbing one flight 
of steps) 
Moderate symptoms 
(shortness of breath 
after walking on flat 
ground) 
Severe symptoms 
(shortness of breath 
at rest; requiring O2 ) 
□ 
□ 
□ 
□ 
Spirometry 
Not done □ 
FEV1 
（% Predicted）： 
             
FEV1 
（L）： 
          
FVC 
（% 
Predicted）： 
            
FVC 
（L）： 
           
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
 
Score 0 
Score 1 
Score 2 
Score 3 
Eyes 
No symptoms 
Mild dry eye symptoms 
not 
affecting 
ADL 
(requirement 
of 
lubricant eye drops ≤ 3 
x per day) 
Moderate 
dry 
eye 
symptoms 
partially 
affecting ADL (requiring 
lubricant eye drops > 3 x 
per day or punctal plugs). 
WITHOUT new vision 
impairment due to KCS 
Severe 
dry 
eye 
symptoms 
significantly 
affecting 
ADL 
(special eyeware to 
relieve 
pain) 
OR 
unable 
to 
work 
because of ocular 
symptoms OR loss 
of vision due to KCS 
□ 
□ 
□ 
□ 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 


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Score 0 
Score 1 
Score 2 
Score 3 
Joints 
And 
Fascia 
No symptoms 
Mild tightness of arms or 
legs, normal or mild 
decreased 
range 
of 
motion (ROM) AND not 
affecting ADL 
Tightness of arms or legs 
OR 
joint 
contractures, 
erythema thought due to 
fasciitis, moderate decrease 
ROM 
AND 
mild 
to 
moderate limitation of ADL 
Contractures WITH 
significant decrease 
of 
ROM 
AND 
significant 
limitation of ADL 
(unable to tie shoes, 
button shirts, dress 
self etc. 
□ 
□ 
□ 
□ 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
P-ROM 
Score 
 
Score         
Not done □ 
Score         
Not done □ 
Score         
Not done □ 
Score         
Not done □ 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
 
Score 0 
Score 1 
Score 2 
Score 3 
Skin 
No BSA 
involved 
1-18% BSA 
19-50% BSA 
>50% BSA 
□ 
□ 
□ 
□ 


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□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
 
Score 0 
Score 1 
Score 2 
Score 3 
Skin 
Features 
Score 
No 
sclerotic 
features 
 
Superficial 
sclerotic 
features “not hidebound” 
(able to pinch) 
Check all that apply: 
□Deep 
sclerotic 
features 
□
“Hidebound” 
(unable to pinch) 
□Impaired mobility 
□Ulceration 
□ 
 
□ 
□ 
If skin features score=3, BSA% of non-moveable sclerosis/fasciitis：                     
Other skin GVHD features (scored by BSA) 
Check all that apply: 
□Maculopapular rash/erythema 
□Lichen planus-like features 
□Sclerotic features 
□Papulosquamous lesions or 
ichthyosis 
□Keratosis pilaris-like 
How would you rate the severity of this patient’s skin and/or joint tightening on the following scale, where 0 is 
not at all severe and 10 is the most severe symptoms possible： 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Symptoms 
not at all 
severe 
 
Most 
severe 
sympto
ms 
possible 
 
 
 
 
 
 
 
 
 
 
Mouth 
Erythema 
None 
0 
Mild or 
moderate 
erythema
（<25%） 
1 
Moderate
（≥25%）or 
Severe erythema
（<25%） 
2 
Severe 
erythema
（≥25%） 
3 
Lichenoid 
None 
0 
Lichen-like 
1 
Lichen-like 
2 
Lichen-like 
3 


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changes
（<25%） 
changes
（25%~50%） 
changes
（>50%） 
Ulcers 
None 
0 
 
 
Ulcers involving
（≤20%） 
3 
Severe 
ulcerations
（>20%） 
6 
 
 
 
 
 
 
 
 
Total score for all mucosal changes  
 
 
 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
Liver labs 
Total serum bilirubin 
(mg/dL) 
ALT 
(U/L) 
ALP 
(U/L) 
                
                 
                 
□Abnormality present but explained entirely by non-GVHD documented cause (specify): 
 
□Abnormality thought to represent GVHD PLUS other causes (specify): 
 
 
Global severity rating 
Where would you rate the severity of this patient’s chronic GVHD symptoms on the following scale, where 0 is 
cGVHD symptoms that are not at all severe and 10 is the most severe cGVHD symptoms possible: 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Not at 
all 
severe 
 
 
 
 
 
 
 
 
 
Most 
severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Additional cGVHD details per organ 
Lungs 
Pulmonary Function 
Tests (PFTs) 
diffusing capacity for carbon 
monoxide (DLCO) 
(single breath, adjusted for 
hemoglobin)                 
 
Residual Volume 
(RV) (L) 
              
 
Total lung capacity 
(TLC) (L) 
              
OTHER SKIN GVHD FEATURES (NOT scored by BSA) 
Check all that apply: 
□Hyperpigmentation 
□Hypopigmentation 
□Poikiloderma 
□Severe or generalized pruritus 
□Hair Involvement 
□Nail Involvement 
Eyes 
Keratoconjunctivitis 
sicca (KCS) 
confirmed by 
ophthalmologist: 
□Yes 
□No 
□Not examined 
OTHER 
cGVHD 
FEATU
RES 
Other indicators, clinical features or complications related to chronic GVHD [check all that apply 
and assign a score to severity (0-3) based on functional impact where applicable; none: 0; mild: 1; 
moderate: 2; severe: 3] 
□Ascites (serositis) _____  
□Pericardial Effusion _____ 
□Pleural Effusion _____ 
□Nephrotic syndrome _____ 
□Myasthenia Gravis _____ 
□Peripheral Neuropathy _____ 
□Polymyositis _____ 
□Others (specify):_____ 
cGVHD
Status 
Since starting BN101/belumosudil, would you say that this patient’s cGvHD is: 
-3 
-2 
-1 
0 
1 
2 
3 
Score 
Very 
much 
worse 
Moderat
ely 
worse 
A little 
worse 
About the 
Same 
A little 
better 
Moderately 
better 
Very 
much 
better 
         
Abstracted from: Lee SJ et al. (Biol Blood Marrow Transplant 2015; 21:984 – 999); Jagasia, et al (Biol Blood Marrow Transplant. 
2015;21:389–401) 
 
 


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Appendix 6 cGVHD Response Assessment 
Response Determination for Chronic GVHD Clinical Trials based on Clinician Assessments 
Organ 
Complete Response 
Partial Response 
Progression 
Skin 
NIH Skin Score 0 after 
previous involvement 
Decrease in NIH Skin Score 
by 1 or more points 
Increase in NIH Skin Score by 
1 or more points, except 0 to 1 
Eyes 
NIH Eye Score 0 after 
previous involvement 
Decrease in NIH Eye Score 
by 1 or more points 
Increase in NIH Eye Score by 
1 or more points, except 0 to 1 
Mouth 
NIH Modified OMRS 0 after 
previous involvement 
Decrease in NIH Modified 
OMRS of 2 or more points 
Increase in NIH Modified 
OMRS of 2 or more points 
Esophagus 
NIH Esophagus Score 0 after 
previous involvement 
Decrease in NIH Esophagus 
Score by 1 or more points 
Increase in NIH Esophagus 
Score by 1 or more points, 
except 0 to 1 
Upper GI 
NIH Upper GI Score 0 after 
previous involvement 
Decrease in NIH Upper GI 
Score by 1 or more points 
Increase in NIH Upper GI 
Score by 1 or more points, 
except 0 to 1 
Lower GI 
NIH Lower GI Score 0 after 
previous involvement 
Decrease in NIH Lower GI 
Score by 1 or more points 
Increase in NIH Lower GI 
Score by 1 or more points, 
except from 0 to 1 
Liver 
Normal ALT, alkaline 
phosphatase, and Total 
bilirubin after previous 
elevation of 1 or more 
Decrease by 50% 
Increase by 2 ✖ULN 
Lungs 
• 
Normal %FEV1 after 
previous involvement 
• 
If PFTs not available, 
NIH Lung Symptom 
Score 0 after previous 
involvement 
• 
Increase 
by 
10% 
predicted 
absolute 
value of %FEV1  
• 
If PFTs not available, 
decrease in NIH Lung 
Symptom Score by 1 
or more points 
• 
Decrease 
by 
10% 
predicted absolute value 
of %FEV1  
• 
If PFTs not available, 
increase in NIH Lung 
Symptom Score by 1 or 
more points, except 0 to 1 
Joints and fascia 
Both NIH Joint and Fascia 
Score 0 and P-ROM score 
25 
after 
previous 
involvement by at least 1 
measure 
Decrease in NIH Joint and 
Fascia Score by 1 or more 
points or increase in P-
ROM score by 1 point for 
any site 
Increase in NIH Joint and 
Fascia Score by 1 or more 
points or decrease in P-ROM 
score by 1 point for any site 
Global 
Clinician 
overall 
severity 
score 0 
Clinician overall severity 
score decreases by 2 or 
more points on a 0-10 scale 
Clinician overall severity score 
increases by 2 or more points 
on a 0-10 scale 
Abstracted from: Lee SJ, Wolff D, Kitko C, et al. Biol Blood Marrow Transplant 2015; 21:984 –999. 
 
 


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Appendix 7 cGVHD Lee Symptom Scale Score 
By circling one number per line, please indicate how much you have been bothered by the following 
problems in the past 7 days: 
Skin 
 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
1. 
 
Abnormal skin 
color 
0 
1 
2 
3 
4 
2. 
 
Rashes 
0 
1 
2 
3 
4 
3. 
 
Thickened skin 
0 
1 
2 
3 
4 
4. 
 
Skin ulcer 
0 
1 
2 
3 
4 
5. 
 
Itchy skin 
0 
1 
2 
3 
4 
Eyes and 
Mouth 
 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
6. 
 
Dry eyes 
0 
1 
2 
3 
4 
7. 
 
Need to use eye 
drops frequently 
0 
1 
2 
3 
4 
8. 
 
Difficulty seeing 
clearly 
0 
1 
2 
3 
4 
9. 
 
Need to avoid 
certain foods due 
to mouth pain 
0 
1 
2 
3 
4 
10.  
Ulcers in mouth 
0 
1 
2 
3 
4 
11.  
Receiving 
nutrition from and 
intravenous line 
or feeding tube 
0 
1 
2 
3 
4 
Breathing 
 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
12.  
Frequent cough 
0 
1 
2 
3 
4 
13.  
Colored sputum 
0 
1 
2 
3 
4 
14.  
Shortness of 
breath with 
exercise 
0 
1 
2 
3 
4 
15.  
Shortness of 
breath at rest 
0 
1 
2 
3 
4 
16.  
Need to use 
oxygen 
0 
1 
2 
3 
4 
Eating 
and 
Digestion 
 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
17.  
Difficulty 
swallowing solid 
foods 
0 
1 
2 
3 
4 


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18.  
Difficulty 
swallowing 
liquids 
0 
1 
2 
3 
4 
19.  
Vomiting 
0 
1 
2 
3 
4 
20.  
Weight loss 
0 
1 
2 
3 
4 
Muscles 
and Joints  
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
21.  
Joint and muscle 
aches 
0 
1 
2 
3 
4 
22.  
Limited joint 
movement 
0 
1 
2 
3 
4 
23.  
Muscle cramps 
0 
1 
2 
3 
4 
24.  
Weak muscled 
0 
1 
2 
3 
4 
Energy 
 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
25.  
Loss of energy 
0 
1 
2 
3 
4 
26.  
Need to sleep 
more/take naps 
0 
1 
2 
3 
4 
27.  
Fevers 
0 
1 
2 
3 
4 
Mental 
Emotional  
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
28.  
Depression 
0 
1 
2 
3 
4 
29.  
Anxiety 
0 
1 
2 
3 
4 
30.  
Difficulty 
sleeping 
0 
1 
2 
3 
4 
 
 
 


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Appendix 8  PROMIS Global Health Score 
Please answer each of the following questions and mark the box by selecting an appropriate answer 
for each question. 
 
 
Excellent 
Very 
good 
Good  
Fair 
Poor 
01 
In general, would you say your health 
is: 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
02 
In general, would you say your 
quality of life is: 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
03 
In general, how would you rate your 
physical health? 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
04 
In general, how would you rate your 
mental health, including your mood 
and your ability to think? 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
05 
In general, how would you rate your 
satisfaction with your social activities 
and relationships? 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
09 
In general, please rate how well you 
carry out your usual social activities 
and roles. (This includes activities at 
home, at work and in your 
community, and responsibilities as a 
parent, child, spouse, employee, 
friend, etc.) 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
 
 
 
Completely  
Mostly  
Moderately  
A little 
Not At 
All 
06 
To what extent are you able to carry 
out your everyday physical activities 
such as walking, climbing stairs, 
carrying groceries, or moving a 
chair?  
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
 
 
In the past 7 days 
Never 
Rarely 
Sometimes 
Often 
Always 
10 
How often have you been bothered 
by emotional problems such as 
feeling anxious, depressed, or 
irritable? 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
 
 
None 
Mild 
Moderate 
Severe 
Very 
Severe 
08 
How would you rate your fatigue on 
average? 
□ 
5 
□ 
4 
□ 
3 
□ 
2 
□ 
1 
07 
How would you rate your pain on 
average? 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No Pain                           Worst Imaginable Pain 


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Appendix 9  cGVHD Activity Assessment-Patient Self Report 
Symptoms 
 
Please rate how severe the following symptoms 
have been in the last 7days. Please fill in the circle 
below from 0 (symptoms has not been present) to 
10 (the symptom was as bad as you can imagine it 
could be) for each item. 
 
 
 
 
 
 
 
 
 
 
 
Not  
Present 
 
 
 
 
 
 
 
As Bad As 
You Can Imagine 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Your skin itching at its WORST? 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
Your skin and/or joint tightening at their WORST? 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
Your mouth sensitivity at its WORST? 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
Your genital discomfort at its WORST? 
(Women-vagina, vulva, or labia) 
(Men-penis) 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
Eyes 
 
What is your main complaint with regard to your eyes? 
 
Please rate how severe this symptom is, from 
0 (not at all severe) to 10 (most severe) 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
Patient Global Ratings: 
 
1. Overall, do you think that your chronic graft versus host disease is mild, moderate or severe? 
1=mild 
2=moderate 
3=severe 
 


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2. Please circle the number indicating how severe your chronic graft versus host disease symptoms are, where 0 is cGVHD symptoms that are not at all 
severe and 10 is the most severe chronic GVHD symptoms possible. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
cGVHD symptoms 
not at all severe 
 
 
 
 
 
Most severe cGVHD  
symptoms possible 
 
 
 
 
 
 
 
 
 
 
 
3. Compared to a month ago, overall would you say that your cGVHD symptoms are: 
+3 = Very much better 
+2 = Moderately better 
+1 = A little better 
0 = About the same 
-1 = A little worse 
-2 = Moderately worse 
-3 = Very much worse 
Abstracted from：Lee SJ, Wolff D, Kitko C, et al. Measuring Therapeutic Response in Chronic Graft-versus-Host Disease. National Institutes of Health Consensus Development Project on 
Criteria for Clinical Trials in Chronic Graftversus-Host Disease: IV. The 2014 Response Criteria Working Group Report. Biol Blood Marrow Transplant 2015;21:984 – 999.  


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Appendix 10  Eastern Cooperative Oncology Group (ECOG) Performance Status 
Score 
Description 
0 
Fully active, able to carry on all pre-disease activities without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature. For example, light housework, office work. 
2 
Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry 
out any work activities. Up and about more than 50% of waking hours). 
3 
Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or 
chair 50% or more of waking hours). 
4 
Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair). 
5 
Death. 
 
 
 


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Appendix 11  Calculation Formula of Creatinine Clearance 
Male： 
Ccr=[(140-Age)×Weight(kg)]/[0.818×Scr (μmol/L)] 
 
Female： 
Ccr=[(140-Age)×Weight(kg)]/[0.818×Scr (μmol/L)] × 0.85 
 
Annotation： 
Ccr= Creatinine Clearance；Scr = Serum Creatinine 
Scr (mg/dL) = Scr (μmol/L) × 0.01131 
 
 


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Appendix 12  Drugs that Induce and Inhibit CYP3A4 
 
Strong  
Moderate 
Weak 
Inducers 
Apalutamide 
Carbamazepine 
Enzalutamide 
Mitotane 
Phenytoin 
Rifampin 
St. John’s wort 
Bosentan 
Efavirenz 
Etravirine 
Phenobarbital 
Primidone 
Armodafinil 
Modafinil 
Rufinamide 
Inhibitiors 
Boceprevir 
Cobicistat 
Conivaptan 
Danoprevir 
Dasabuvir 
Elvitegravir 
Grapefruit juice 
Indinavir 
Itraconazole 
Ketoconazole 
Lopinavir 
Paritaprevir 
Ombitasvir 
Posaconazole 
Ritonavir 
Saquinavir 
Telaprevir 
Tipranavir 
Telithromycin 
Troleandomycin 
Voriconazole 
Aprepitant 
Ciprofloxacin 
Kaunivartan 
Crizotinib 
Cyclosporine 
Diltiazem 
Dronedarone 
Erythromycin 
Fluconazole 
Fluvoxamine 
Imatinib 
Tofisopam 
Verapamil 
Chlorzoxazone 
Cilostazol 
Cimetidine 
Clotrimazole 
Fosaprepitant 
Istradefylline 
Ivacaftor 
Lomitapide 
Ranitidine 
Ranolazine 
Ticagrelor 
This is not a comprehensive list, and all concomitant medications should be evaluated for possible interactions with 
BN101/belumosudil. 
Data Source：
https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm 
 
 


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Appendix 13 Drugs that Induce and Inhibit CYP1A2 
 
Strong 
Moderate 
Weak 
Inducers 
- 
Phenytoin  
Rifampin  
Ritonavir  
Smoking Teriflunomide 
- 
Inhibitors 
Ciprofloxacin Enoxacin 
Fluvoxamine 
Methoxsalen Mexiletine  
Oral contraceptives 
Acyclovir Allopurinol 
Cimetidine Peginterferon 
α-2a Piperine Zileuton 
This is not a comprehensive list, and all concomitant medications should be evaluated for possible interactions with 
BN101/belumosudil. 
Data Source：
https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm 
 
 


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Appendix 9 Drugs that Prolong QT/QTc 
Generic Name 
Aclarubicin 
Hydroxychloroquine 
Amiodarone 
Ibogaine 
Anagrelide 
Ibutilid 
Arsenic trioxide  
Levofloxacin 
Astemizole 
Levomepromazine 
Azithromycin 
Levomethadyl acetate 
Bepridil 
Levosulpiride 
Chloroquine 
Mesoridazine 
Chlorpromazine 
Methadone 
Chlorprothixene 
Moxifloxacin 
Cilostazol 
Nifekalant 
Ciprofloxacin 
Ondansetron 
Cisapride 
Oxaliplatin 
Citalopram 
Papaverine HCl 
Clarithromycin 
Pentamidine 
Cocaine 
Pimozide 
Disopyramide 
Probucol 
Dofetilide 
Procainamide 
Domperidone 
Propofol 
Donepezil  
Quinidine 
Dronedarone 
Roxithromycin 
Droperidol 
Sevoflurane 
Erythromycin 
Sotalol 
Escitalopram 
Sparfloxacin 
Flecainide 
Sulpiride 
Fluconazole 
Sultopride 
Gatifloxacin 
Terfenadine 
Grepafloxacin 
Terlipressin 
Halofantrine 
Terodiline 
Haloperido 
Thioridazine 
Dihydroquinidine 
Vandetanib 
This is not a comprehensive list, and all concomitant medications should be evaluated for possible interactions with 
BN101/belumosudil. 
Data Source：https://www.crediblemeds.org/pdftemp/pdf/CombinedList.pdf (30 Dec 2019) 
 
 


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Version Date: 25 Feb 2022 
Appendix 10 Equivalent Dose of Corticosteroid Hormone 
Class of Drug 
Name of Drug 
Equivalent Dose（mg） 
Short-acting 
Hydrocortisone 
20 
Cortisone 
25 
Medium-acting 
Prednisone 
5 
Prednisolone 
5 
Methylprednisone 
4 
Long-acting 
Triamcinolone acetonide 
4 
Betamethasone 
0.60 
Dexamethasone 
0.75 
Hydrocortisone 1 = Cortisone 0.8 = Prednisone 4 = Prednisolone 4 = Methylprednisone 5 = Triamcinolone 
acetonide 5 = Betamethasone 25 = Dexamethasone 20 
Annotation： 
The ratio of anti-inflammatory effect is based on counting hydrocortisone as 1. The equivalent dose is counted with a standard of 
hydrocortisone.  
Data Source：http://news.medlive.cn/imm/info-progress/show-150532_166.html 
 

SAP_001.pdf: 
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A Phase 2, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of 
BN101/belumosudil in Subjects with Chronic Graft Versus Host Disease (cGVHD) After at 
Least 1 Prior Line of Systemic Therapy 
 
BN101-201 
 
 
 
 
Statistical Analysis Plan 
 
 
 
Sponsor：BK Pharmaceuticals Limited 
Agent：BioNova Pharmaceuticals Limited 
 
Version: 1.0 
Date：17-Jun-2022 
 
 
 
 
 
 
 


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Document History 
Version 
Date 
Author 
Description 
1.0 
17-Jun-2022  
Linlin Dai 
Original Document 
 
 
 
 
 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
 
1. 
ABBREVIATIONS .............................................................................................................. 4 
2. 
INTRODUCTION ................................................................................................................ 6 
3. 
STUDY OBJECTIVE ........................................................................................................... 6 
4. 
STUDY DESIGN ................................................................................................................. 6 
5. 
STUDY ENDPOINTS .......................................................................................................... 7 
5.1. 
Efficacy Endpoints ......................................................................................................... 7 
5.2. 
Safety Endpoints .......................................................................................................... 11 
5.3. 
Pharmacokinetic Variables ........................................................................................... 12 
5.4. 
Protocol Deviation........................................................................................................ 12 
5.5. 
Treatment Compliance and Exposure .......................................................................... 13 
6. 
STATISTICAL HYPOTHESIS .......................................................................................... 13 
7. 
ANALYSIS POPULATION ............................................................................................... 13 
8. 
STATISTICAL METHODS ............................................................................................... 14 
8.1. 
General Consideration .................................................................................................. 14 
8.2. 
Handling of Data .......................................................................................................... 15 
8.3. 
Study Population .......................................................................................................... 16 
8.4. 
Efficacy Analyses ......................................................................................................... 18 
8.5. 
Safety Analysis ............................................................................................................. 22 
8.6. 
Pharmacokinetic Analyses ........................................................................................... 24 
8.7. 
Other Analyses ............................................................................................................. 24 
9. 
REFERENCES ...................................................................................... 错误!未定义书签。 


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1. Abbreviations 
ADI 
Actual dose intensity 
ADL 
Activity of daily life 
AE 
Adverse event 
aGVHD 
Acute graft versus host disease 
ALB 
Albumin  
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
Ca 
Calcium 
cGVHD 
Chronic graft versus host disease 
CI 
Confidence interval 
Cl 
Chloride  
CNI 
Calcineurin inhibitor 
CR 
Complete response 
CRF 
Case report form 
DoR 
Duration of response 
ECOG 
Eastern Cooperative Oncology Group 
ECP 
Extracorporeal photopheresis 
EOT 
End of treatment 
FFS 
Failure free survival 
GGT 
Gamma-glutamyl transferase 
GLU 
Glucose  
GVHD 
Graft versus host disease 
Hb 
Hemoglobin  
K 
Potassium  
LR 
Lack of response 
LR-M 
Lack of response - mixed 
LR-P 
Lack of response - progression 
LR-U 
Lack of response - unchanged 
MedDRA 
Medical dictionary for regulatory activities 
mITT 
Modified intent-to-treatment 
Na 
Sodium 
ORR 
Overall response rate 
OS 
Overall survival 
PDI 
Planned dose intensity 
PK 
Pharmacokinetics  
PLT 
Platelet  
PPS 
Per - protocol set 
PR 
Partial response 
PROMIS 
Patient reported outcomes measurement information 


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system 
PS 
Performance status 
PT 
Preferred term 
PTE 
Pre-treatment event 
QD 
Once daily 
QOD 
Once every other day 
RBC 
Red blood cell  
RDI 
Relative dose intensity 
SAE 
Serious adverse event 
SMQ 
Standard MedDRA query 
Cr 
Creatinine 
SOC 
System organ class 
SS 
Safety analysis set 
TBIL 
Total bilirubin  
TEAE 
Treatment emergent adverse event 
TP 
Total protein 
TTNT 
Time to new treatment 
TTR 
Time to response 
UA 
Uric acid 
WBC 
White blood cell 
 


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2. Introduction 
The objective of the BN101-201 study is to evaluate the efficacy and safety of BN101 in the 
patients with cGVHD who have previously been treated with one to five prior lines of systemic 
therapy. 
This Statistical Analysis Plan (SAP) describes data-handling and statistical procedures to be used 
for the analysis and reporting of efficacy and safety data collected under Study BN101-201 and 
presented in the clinical study report (CSR). This SAP has been developed and finalized prior to 
locking the clinical database. Pharmacokinetic (PK) analyses will be described in separate 
documents. 
3. Study Objective 
Primary objective： 
• 
To evaluate the efficacy and safety of BN101/belumosudil in subjects with cGVHD who 
had previously been treated with at least 1 prior line of systemic therapy. 
Secondary objective： 
• 
To evaluate the PK profile of BN101/belumosudil in subjects with cGVHD who had 
previously been treated with at least 1 prior line of systemic therapy; 
• 
To evaluate other efficacy endpoints of BN101/belumosudil in subjects with cGVHD who 
had previously been treated with at least 1 prior line of systemic therapy. 
Exploratory objective： 
• 
To evaluate changes in the Patient-Reported Outcomes Measurement Information System 
(PROMIS) Global Health sub-scores of physical and mental functioning 
4. Study Design 
BN101-201 is a phase 2, multicenter, open label, single-arm study in patients with cGVHD who 
have previously been treated with one to five prior lines of systemic therapy. It intends to enroll 
30 Chinese cGVHD patients and to evaluate the efficacy, safety, and PK profile of 
BN101/belumosudil in Chinese cGVHD patients. 
The study enrollment period is estimated to be 6 months. 6 months after the last patient 
enrollment, the database will be locked and the primary analysis will be conducted. After 
primary analysis, all patients will be followed up for additional 6 months and a follow up 
analysis will be conducted 12 months after the last patient enrollment. 
Eligible patients who have signed informed consent will be enrolled to receive 
BN101/belumosudil (every 28-day cycle) until cGVHD progression, intolerable toxicity, 
initiation of a new cGVHD therapy, recurrence of hematological neoplasm, loss to follow-up, 


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withdrawal of consent, or death, whichever occurrs first. During study, concomitant treatment 
with standard of care systemic cGVHD therapies such as corticosteroids, calcineurin inhibitors 
(tacrolimus, cyclosporine), sirolimus, MMF, or extracorporeal photopheresis (ECP), are 
permitted as long as the patient has been on a stable dose / regimen of these per the eligibility 
criteria. Initiation of new systemic cGVHD therapy while on study is not permitted. Response 
criteria will be assessed after cycles 1, 2, 3 and 4 and then after every other cycle thereafter (i.e. 
on Day 1 of Cycle 2, 3, 4, 5, 7, 9, 11 etc). For patients assessed as "Lack of Response - Mixed" 
and "Lack of Response - Progression" [Evaluated by the investigator based on the National 
Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in 
cGVHD(2014), hereinafter referred to as the NIH Consensus Criteria (2014) ], if the investigator 
believed that these patients could continue to benefit from treatment with BN101/belumosudil, 
the treatment may be continued after a written application was submitted, and approval from the 
Sponsor's Medical Monitor as well as documentation of the patient's willingness to continue 
treatment was obtained. For patients who did not achieve any response after 12 cycles of 
BN101/belumosudil treatment, they should discontinue the study medication and withdraw from 
the study if in the investigator’s judgment there is no evidence of clinical benefit (e.g., 
improvements in organ score, improvements in Lee symptom scores, reductions of 
corticosteroid/tacrolimus doses). For patients whose cGVHD has not progressed at the time of 
discontinuation of the study treatment and who come off study for reasons other than AEs should 
be tapered off BN101/belumosudil by reducing the dose every other week (200mg QD → 200mg 
QOD → discontinue). 
5. Study Endpoints 
5.1. Efficacy Endpoints 
5.1.1. Primary Efficacy Endpoints 
The primary efficacy endpoint is the overall response rate (ORR) as assessed by the investigators 
based upon the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD. 
Response is assessed using individual scores from ten systems (Skin, Eyes, Mouth, Esophagus, 
Upper GI, Lower GI, Liver, Lungs, Joints and Fascia and Global Severity Rating (GSR)). 
Response is assessed with respect to the baseline (Cycle 1, Day 1 (C1D1)) cGVHD assessment. 
The overall response at each assessment time point will be categorized as Complete Response 
(CR), Partial Response (PR), or Lack of Response (LR), where LR includes the response status 
of unchanged, mixed, or progression as defined in Table 1. 
The ORR is defined as the proportion of patients with a best response meeting the overall 
response criteria assessment of CR or PR at any post-baseline response assessment. 
If a treated patient is lost to follow up without response assessment, this patient will be counted 
as a non-responder. Any response on and after new systemic cGVHD treatment will be censored 
as non-response. 
Table 1: cGVHD Response Definitions 


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Response 
Definition 
Complete Response (CR) 
Resolution of all manifestations of cGVHD in each organ or site. 
Partial Response (PR) 
Improvement in at least one organ or site without progression in 
any other organ or site. 
Lack of Response (LR) 
Mixed (LR-M) 
Complete or partial response in at least one organ accompanied by 
progression in another organ* 
Unchanged (LR-U) 
Outcomes that do not meet the criteria for complete response, 
partial response, progression or mixed response 
Progression (LR-P) 
Progression in at least one organ or site without a response in any 
other organ or site 
* Considered progression for the purposes of analysis 
 
5.1.2. Secondary Efficacy Endpoints 
Secondary efficacy endpoints include Duration of Response (DoR), Lee Symptom Scale Score 
(LSS), Response by Organ System, Time to Response, Time to Next Therapy, Corticosteroid 
Dose, Calcineurin Inhibitor (CNI) Dose, Failure Free Survival (FFS), Overall Survival (OS), 
Change in cGVHD severity using the Clinician-Reported Global cGVHD Activity Assessment, 
and Change in symptom activity using the cGVHD Activity Assessment Patient Self-Report.  
DoR 
Four definitions of DoR are as following: 
The primary definition of DoR is the time 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). 
The secondary definition of DoR is the time from first documentation of response to the time of 
first documentation of lack of response. 
The tertiary definition of DoR is the time from first documentation of response to the time of 
initiation of new systemic cGVHD therapy. 
The quaternary definition of DoR is the time from first documentation of response to the time of 
first documentation of lack of response (as the secondary definition) but with durations summed 
for multiple response / lack of response episodes. 
The DoR will be reported only for responders. And the censoring rules in Table 2 will be applied. 
Lee Symptom Scale Score (LSS) 


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Lee cGVHD Symptom Scale will be assessed on Day 1 of Cycles 2-5, then on Day 1 of every 
other Cycle thereafter and EOT. The questionnaire consists 30 items of 7 domains: skin, eyes 
and mouth, breathing, eating and digestion, muscles and joints, energy, and emotional. Each 
question is scored 0, 1, 2, 3 or 4.  
A domain score will be calculated for each domain by taking the mean of all items completed if 
more than 50% were answered and normalizing to a 0 to 100 scale. A summary score will be 
calculated as average of all domain scores if more than 50% of them are nonmissing. A higher 
score indicated more bothersome symptoms. 7 points difference on the summary score of 
cGVHD symptom scale was found to be clinically meaningful.  
Raw Score = （I1 + ··· + Im ）/ m， m is the number of items have nonmissing value in a 
domain.  
Domain Score = Raw Score / 4 *100。 
Summary Score = （Domain Score1 + ··· + Domain Scoren）/ n，n is the number of 
domains have nonmissing domain scores. 
Response by Organ System 
Response assessment by physician for the nie individual organs (skin, eyes, mouth, esophagus, 
upper GI, lower GI, liber, lungs and joints and fascia) plus global severity rating will be collected 
in eCRF. 
Time to Response (TTR) 
TTR is defined as the time from first treatment to the time of first documentation of response. 
Time to Next Therapy (TTNT) 
TTNT is defined as the time from first treatment to the time of new systemic cGVHD treatment, 
censored by last response assessment or long term follow up assessment, which ever is the latest 
and available.  
Corticosteroid Dose 
Corticosteroid doses will be presented as mg/kg/day prednisone equivalent dose. If a patient is 
not using prednisone as the systemic corticosteroid, then the prednisone dose equivalent will be 
determined according to following conversion ratios: 
1mg prednisone is equivalent to: 
• 
4mg Hydrocortisone 
• 
0.8mg Methylprednisolone 
• 
0.15mg Dexamethasone 


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• 
1mg Prednisolone 
• 
0.8mg Triamcinolone 
Transient increase in corticosteroid dosing (not exceeding 1mg/kg/day prednisone equivalent) is 
permitted for the treatment of cGVHD flare, but dose must be reduced back to the pre-enrollment 
dose within 6 weeks. If the dose remains elevated for more than 6 weeks, this will be considered 
a BN101/belumosudil treatment failure. More than 2 episodes of cGVHD flare requiring 
increased corticosteroid in the first month of BN101/belumosudil treatment will also be 
considered a BN101/belumosudil treatment failure. 
Calcineurin Inhibitor (CNI) Dose 
CNI includes systemic tacrolimus and cyclosporine. 
Failure Free Survival (FFS) 
FFS is defined as the absence of new cGVHD systemic therapy, non-relapse mortality and 
recurrent malignancy (e.g. underlying disease) and is censored by last response assessment or 
long term follow up assessment, whichever is the latest and available.  
Overall Survival (OS) 
OS is defined as time from first dose of BN101/belumosudil to the date of death due to any cause. 
Change in cGVHD severity using the Clinician-Reported Global cGVHD Activity 
Assessment 
The Clinician-reported global cGVHD Activity Assessment is a 0-10 point numeric rating scale 
with a score 0 indicating “cGVHD symptoms not at all severe” and a score of 10 being “most 
severe cGVHD symptoms possible”. The activities are assessed on Day 1 of each cycle from 
Cycle 1 Day 1 to EOT. 
Change in symptom activity using the cGVHD Activity Assessment Patient Self-Report 
The symptom activity item is a 0-10-point numeric rating scale with a score of 0 indicating 
“cGVHD symptoms not at all severe” and a score of 10 being “most severe cGVHD symptoms 
possible”. The status reported by patients are categorized as none, mild, moderate, and severe. 
The comparison of cGVHD symptoms to a month ago will also be reported by patients, rating 
from -3 (very much worse) to +3 (very much better). 
5.1.3. Exploratory Endpoints  
Patient-Reported Outcomes Measurement Information System (PROMIS), a state-of-the-science 
PRO measurement system, was developed using mixed qualitative and quantitative methods and 
uses item response theory-calibrated item banks for numerous patient-reported symptoms and 
functional domains. The PROMIS Global Health 10 measure comprises ten items with two 
summary scores for physical and mental functioning with higher scores indicating better 


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functioning. Those two summary scores will be calculated using the Assessment Center Scoring 
Service (https://www.assessmentcenter.net/ac_scoringservice) from raw data.  
5.2. Safety Endpoints 
5.2.1. Adverse Events 
Adverse Event 
Adverse event (AE) is defined as any untoward medical occurrence in a patient administered the 
study medication and which does not necessarily have to have a causal relationship with the 
treatment. 
Treatment Emergent Adverse Event 
Treatment emergent adverse events (TEAE) are any AEs occurring or worsening in severity after 
the first administration of study medication.  
Significant Adverse Event 
Significant adverse events are any AEs leading to additional pertinent intervention (such as dose 
interruption, dose reduction or dose discontinuation).  
Causality of Adverse Event 
The causality with BN101/belumosudil will be classified into following 5 classes: definitely 
related, possibly related, unlikely related, not related, and not determined. Definitely related, 
possibly related, and not determined will be considered related in the analysis of related AEs. 
Serious Adverse Event（SAE） 
Serious adverse events (SAE) are any AE which happens during any study period (screening 
period, treatment period, follow up period) with any dose of the study medication and which 
meet one or more following criteria. Treatment emergent SAE will be summarized in the 
analysis. 
o 
Result in death 
o 
Life threatening 
o 
Requires inpatient hospitalization or prolongation of existing hospitalization 
o 
Result in persistent or significant disability / incapacity 
o 
Result in a congenital anomaly / birth defect 
o 
Other important medical events 
Death 


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All AEs leading to death will be recorded in CRF. Death report will also be collected in CRF. 
Severity of Adverse Events 
Adverse event will be graded using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0： 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL) (instrumental ADL refer to preparing 
meals, shopping for groceries or clothes, using the telephone, managing money, etc) 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self care ADL (self care ADL refer 
to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden) 
Grade 4: Life threatening consequences; urgent intervention indicated. 
Grade 5: Death related to AE. 
5.2.2. Vital Signs 
Body temperature, pulse, blood pressure (systolic pressure and diastolic pressure) and overall 
assessment will be collected in CRF. 
5.2.3. 12 Lead-ECG 
12 lead-ECG results (heart rate, RR interval, PR interval, QT interval, QTcB interval, QTcF 
interval, QRS wave and overall assessment) will be collected in CRF.  
5.2.4. Laboratory Evaluations 
Hematology, chemistry, and urinalysis will be collected in CRF. 
5.2.5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score 
ECOG PS score will be collected in CRF. 
5.3. Pharmacokinetic Variables 
Pharmacokinetic variables will be presented in a separate PK analysis plan. 
5.4. Protocol Deviation 
All protocol deviations will be identified and classified as major or minor (as defined below) 
before the clinical database lock.  


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Major Deviations: Protocol deviation that may impact the accuracy, and/or reliability of the 
study data or that may impact patient rights, safety or well-being. 
Minor Deviations: Protocol deviation that does not impact the accuracy, and/or reliability of the 
study data or patient rights, safety or well-being. 
5.5. Treatment Compliance and Exposure 
The extent of BN101/belumosudil exposure will be assessed using the duration of 
BN101/belumosudil treatment.  
Duration of treatment (days) = last dose date – first dose date + 1 regardless of unplanned 
intermittent discontinuations.  
The cumulative duration of treatment will be provided, defined as the sum of the duration of 
treatment for all patients, and will be expressed in patient years. 
The relative dose intensity (RDI) will be presented. The RDI is defined as: 
RDI (%) = 100% * ADI (mg/day) / PDI (mg/day) 。 
Where ADI and PDI are the actual dose intensity and planned dose intensity, respectively:： 
ADI (mg/day) = actual cumulative dose (mg) / duration of treatment (days) 
PDI (mg/day) = planned cumulative dose (mg) / duration of treatment (days) 
The planned cumulative dose is the planned daily dose * duration of treatment, while the actual 
cumulative dose is the sum of actual doses received over the duration of treatment. The actual 
total dose will incorporate information of dose reduction and dose interruptions captured in the 
CRF. 
6. Statistical Hypothesis  
Since this study intend to evaluate the consistency of the efficacy, safety and PK profile of 
belumosudil between Chinese cGVHD patients and Caucasian cGVHD patients for the purpose 
of bridging the results of KD025-213 study, no formal hypothesis testing will be performed. All 
statistical analyses will be descriptive. 
7. Analysis Population 
Modified Intent-to-treat (mITT) 
mITT: The primary population for efficacy analyses will be a modified Intent to treat (mITT) 
population defined as all enrolled patients who receive at least one dose of study medication. 
The mITT population will be used for tables of demography, baseline characteristics and efficacy. 


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Responder: The responder population is defined as patients in the mITT population that achieved 
a partial or complete response at any post-baseline response assessment. 
Nonresponder: The nonresponder population is defined as anyone in mITT population that is not 
a responder. 
The responder and nonresponder populations will be used for some subgroup analyses. 
Safety Set (SS) 
The safety population is defined as all enrolled patients who receive at least one dose of study 
medication and have at least one post-baseline safety assessment. Safety population will be used 
for all safety analyses.  
Per-protocol Set（PPS） 
The per-protocol population is defined as a subset of mITT, including all enrolled patients who 
receive at least one dose of study medication without major protocol deviations. PPS will be used 
for sensitivity analyses of primary efficacy analysis. 
8. Statistical Methods 
8.1. General Consideration 
In the line listing, subject ID (site ID-patient screening number) will be the only universal 
identifier for the patient. 
General rule for the statistical description: continuous variables will be summarized by 
descriptive statistics of mean, median, standard deviation, minimum and maximum. Categorical 
variables will be summarized with counts and corresponding percentages.  
All analyses will be conducted using SAS version 9.4 or higher. 
Baseline 
Baseline is defined as the last non-missing measurement or assessment taken on or prior to first 
administration of the study medication.  
Study Day 
Study day will be calculated from the date of first administration of the study medication.  
If the date of event / assessment / sample collection is prior to the first administration of the 
study medication: 
Study day = date of event / assessment / sample collection – date of first administration of the 
study medication 
The day before the date of first dose will be study day -1. 


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If the date of event / assessment / sample collection is after the first administration of the study 
medication: 
Study day = date of event / assessment / sample collection – date of first administration of the 
study medication +1 
The day of the first administration of the study medication is study day 1. 
Unless otherwise specified, unscheduled measurements will not be included in the by-visit 
summaries, but will contribute to best / worst case value, minimum / maximum changes, or 
abnormal or significant observations where required (e.g. shift table). 
8.2. Handling of Data 
8.2.1. Incomplete or Missing Data 
Unless otherwise specified, the missing data will not be imputed. If the missing data is 
categorical, it should be classified as “missing” or “unknown”. 
Incomplete or Missing Start Date and End Date of AE, Prior / Concomitant Medication, Prior / 
Concomitant Non-medication Treatment 
Imputation of missing start date and end date of AE, prior/concomitant medication, 
prior/concomitant non-medication treatment is intended to decide the precedence relationship of 
the event relative to the first administration of the study medication. Unimputed date will be 
presented in the listing. 
• 
Incomplete or Missing Onset Date 
If onset year and month are known and onset year and month are prior to the year and month of 
first dose of study treatment, the onset date will be imputed as the 1st day of onset month. If onset 
year and month are equal to the year and month of first dose of study treatment, then the onset 
date will be imputed as the date of first dose of study treatment. 
If only onset year is known, then the onset date will be imputed as January 1st. If onset year is 
equal to the year of first dose of study treatment, then the onset date will be imputed as the date 
of first dose of study treatment. 
If onset year, month and date are all missing, then the onset date will be imputed as the date of 
first dose of study treatment. 
Note: when the onset date is imputed, it should be on or prior to the end date of event. 
• 
Incomplete or Missing End Date 
If end year and month are known, the end date will be imputed with the last day of end month. If 
the imputed date is later than the latest assessment date, then the end date will be imputed as the 
latest assessment date. 


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If end year is known, the end date will be imputed as the December 31st. If the imputed date is 
later than the latest assessment date, then the end date will be imputed as the latest assessment 
date. 
If end year, month and date are all missing, it should be determined whether the event is ongoing. 
If the variable of ongoing or not is yes or missing, then the end date will not be imputed. If the 
variable of ongoing or not is not, then the end date will be imputed as the latest assessment date.  
Incomplete or Missing Event Date in Time to Event Analyses 
In time to event analyses, if the year and month of event are known, the event date will be 
imputed conservatively. If the event is not anticipated, then the event date will be imputed as the 
1st day of the month. If the event is neutral, then the date will be imputed as the 15th of the month. 
If the event is anticipated, then the event date will be imputed as the last day of the month.  
8.2.2. Derived and Transformed Data 
Data will not be derived or transformed except the necessary calculation for end points based on 
data collected in CRF. Regarding the outliers, queries will be raised to data manager and they 
should be resolved or confirmed before database lock. 
8.3. Study Population 
8.3.1. Patient Disposition 
A disposition of all enrolled patients will be summarized. The number and percentage of patients 
discontinuing from the study and the primary reason for discontinuation will be summarized. 
8.3.2. Protocol Deviation 
Major protocol deviations will be categorized by deviation type (e.g. Entry/eligibility, use of 
excluded medication). The subject incidence of major protocol deviations will be summarized 
overall and by deviation category. All major protocol deviations will be presented in a listing as 
well. 
8.3.3. Demographic 
Patient demographics and baseline characteristics will be summarized for the mITT population. 
Descriptive statistics will be provided for age, height, weight, and body mass index (BMI). 
Frequencies and percentages will be tabulated for sex, ethnicity, and Eastern Cooperative 
Oncology Group (ECOG) performance status (PS) score. 
8.3.4. Medical History 
Medical history will be summarized by primary system organ class (SOC) and preferred term 
(PT). Medical history will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA, Version 25.0 or higher) terminology. Frequencies and percentages will be tabulated 
for medical history by SOC and PT. 


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8.3.5. Transplant History 
Transplant history will be summarized for: 
• 
Auto-transplant (Yes/No) 
• 
Auto-transplant number 
• 
Indication for transplant 
• 
Allo-transplant number 
• 
HLA match (matched, unmatched) 
• 
Stem cell type (bone marrow, peripheral blood, bone marrow + peripheral blood, cord 
blood) 
• 
Donor source (related, unrelated) 
• 
Conditioning regimen (myeloablative, nonmyeloablative) 
• 
Donor age 
• 
Donor gender 
• 
Donor CMV serostatus 
• 
Recipient CMV serostatus 
• 
Prophylaxis for GVHD 
8.3.6. GVHD History 
The baseline characteristics of GVHD will be summarized for: 
• 
Prior aGVHD 
• 
Time from transplant to cGVHD diagnosis 
• 
Time from cGVHD diagnosis to enrollment 
• 
Time from transplant to enrollment 
• 
cGVHD severity: mild / moderate / severe 
• 
Number of organs involved at baseline 
• 
Organ involvement at baseline per NIH criteria 


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8.3.7. Prior Therapies for cGVHD 
Prior therapies for cGVHD will be summarized for:  
Number of prior lines of systemic cGVHD therapy 
Prior systemic cGVHD therapies 
Best response to the recent systemic therapy 
8.3.8. Treatment Compliance and Exposure 
Treatment compliance and exposure will be analyzed on mITT population. 
Duration of treatment and duration of follow up will be summarized as a continuous variable and 
also categorically by numbers and percentages for each category (0-3 months, 3-6 months, 6-9 
months, >9 months).  
Descriptive summary statistics of cumulative exposure (patient year), actual cumulative dose 
(mg), ADI (mg/day), RDI (%) and RDI as a categorical endpoint (>95%, ≤95%) will be 
presented. 
Number and percentage of patients for each RDI category (<80%, 80-100%, >100%) will be 
summarized by visit. 
Number and percentage of patients with dose reduction and dose interruption will be 
summarized. 
8.4. Efficacy Analyses 
Analyses for primary endpoint will be based on mITT and PPS. Other efficacy analyses will be 
based on mITT unless otherwise specified. 
8.4.1. Analyses for Primary Endpoints 
ORR（%）= （the number of patients with a best response meeting the criteria of CR or PR at 
any post-baseline response assessment / the total number of patients in the analysis set）
*100%。 
ORR will be calculated based on mITT and PPS. Point estimate and 95% confidence interval and 
97.5% confidence interval (Clopper-Pearson (exact) method and Normal Approximation method) 
of ORR will be provided.  
8.4.2. Analyses for Secondary Endpoints 
DoR 


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DoR will be analysed only based on responder population. Kaplan-Meier plots and descriptive 
statistics of DoR will be provided. The censoring rules in Table 2 will be applied. Landmark 
analyses with number and percentage of patients with response sustained for ≥12, ≥16,  ≥20, ≥24, 
≥32, ≥40 and ≥48 weeks will be provided.  
Table 2 Censoring Rules for Duration of Response 
DoR 
Events 
Censoring 
Primary 
• Deterioration from best response 
• Initiation of new systemic therapy for cGVHD 
• Death 
If deterioration from best response or initiation of new 
systemic therapy happens immediately after two or more 
missed response assessments, the event date should be set 
as four weeks (one cycle) after last documented response 
assessment prior this event. 
Last documented 
response assessment 
Secondary 
• Documented LR 
• Initiation of new systemic therapy for cGVHD  
• Death 
If LR or initiation of new systemic therapy happens 
immediately after 
two or more missed response 
assessments, the event date should be set as four weeks 
(one cycle) after last documented response assessment 
prior this event.  
Tertiary 
• Initiation of new systemic therapy for cGVHD 
• Death 
Last response 
assessment or long 
term follow up 
assessment, 
whichever is the 
latest and available.  
Quaternary • LR 
• Initiation of new systemic therapy for cGVHD  
• Death 
With summation of DoR from multiple episodes. 
Same with censoring 
rule for primary and 
secondary. 
Lee Symptom Scale Score (LSS) 
The analyses will be performed based on mITT, responder and nonresponder population. The 
analyses will include: 
• 
Both scores and change from baseline values (summary score and domain scores) will be 
summarized as continuous variables by visit. 
• 
Number and percent of patients with a ≥7 point reduction (7-PtR) from baseline. 


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• 
Number and percent of patients with a 7-PtR from baseline on 2 consecutive assessments. 
• 
Duration of a 7-PtR (DO7-PtR) (defined as time from documentation of the first ≥7-point 
resuction to the first documentation of less than 7-point reduction). If there are multiple 
episodes, the DO7-PtR will be measured as the sum of DO7-PtR from all episodes. 
Response by Organ System 
The best response (CR, PR) for the nine individual organs plus global severity rating will be 
summarized. Time to response at the organ level will also be evaluated. Descriptive statistics and 
plots of cumulative number and percentage of responders over time will be provided. Two series 
of percentages will be presented: 
• 
With total number of patients in mITT with involvement of the given organ at baseline as 
denominator 
• 
With numbers of patients in the responder population with involvement of the given organ at 
baseline as denominator 
Time to Response (TTR) 
Descriptive statistics and plots of cumulative number and percent of responders over time will be 
provided. TTR analyses will only be conducted for the responder population. 
Time to Next Therapy (TTNT) 
TTNT will be analysed by the Kaplan-Meier survival method as well as the landmark analysis at 
3, 6, 9, and 12 months. 
Corticosteroid Dose 
Corticosteroid doses will be presented as prednisone equivalent dose. Descriptive statistics for 
the mITT population, responder / nonresponder populations will be provided for: 
• 
Systemic corticosteroid dose over time 
• 
Change and percent change from baseline (C1D1) to the greatest corticosteroid dose 
reduction during BN101/belumosudil treatment period 
• 
Number and percentage of patients who reduced systemic corticosteroid dose during 
BN101/belumosudil treatment period 
• 
Number and percentage of patients who ever discontinued systemic corticosteroid usage for 
over 28 days during BN101/belumosudil treatment period 
The above analyses will be censored on or after new systemic cGVHD treatment. 
Calcineurin Inhibitor (CNI) Dose 


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CNI includes systemic tacrolimus and cyclosporine. Descriptive statistics will be provided for: 
• 
Number and percentage of patients who reduced CNI dose during BN101/belumosudil 
treatment period 
• 
Number and percentage of patients who ever discontinued CNI during BN101/belumosudil 
treatment period  
Failure Free Survival (FFS) 
Kaplan-Meier plots, descriptive statistics of FFS and landmark FFS at 3, 6, 9, and 12 months will 
be provided. In addition, analyses for the three components of FFS will also be provided. 
Overall Survival (OS) 
Kaplan-Meier plots, descriptive statistics of OS and landmark OS at 3, 6, 9, and 12 months will 
be provided. 
Change in cGVHD severity using the Clinician-Reported Global cGVHD Activity 
Assessment 
Change from baseline in cGVHD severity based on the Clinician-reported global cGVHD 
Activity Assessment will be summarized as a categorical endpoint at all scheduled assessment 
visits. 
Change in symptom activity using the cGVHD Activity Assessment Patient Self-Report 
Changes in cGVHD symptoms based on global cGVHD Activity Assessment by the Patient Self-
Report will be summarized as a continuous endpoint at all scheduled assessment visits. Both 
scores as well as the change-from-baseline values will be presented. 
The summary of the change-from-baseline of Global Severity Rating on categorical status and 
the summary of comparison of cGVHD to a month ago will also be presented. 
The number and percentage of patients reporting none, mild, moderate, and severe cGVHD will 
be summarized by visit. 
8.4.3. Additional Analyses 
Exploratory Analyses – PROMIS Global Health Scores 
 
The PROMIS Global Health 10 measure comprises ten items with two summary scores for 
physical and mental functioning. The analyses will be performed on mITT, responder and 
nonresponder populations. The analyses will include: 


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• 
Both raw scores and change-from-baseline values (physical and mental domains) will be 
summarized as continuous variables by visit 
• 
Number and percentage of patients with a ≥4.7-point reduction from baseline (C1D1) 
• 
Number and percentage of patients with a ≥4.7-point increase from baseline (C1D1) 
8.5. Safety Analysis 
Safety analyses will be conducted on the safety analysis set. Safety analyses will include AEs, 
SAEs, vital sign measurements, clinical laboratory evaluations (hematology, chemistry) and 
ECGs. 
8.5.1. Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) dictionary 
(Version 25.0 or higher). All AEs (including SAEs) will be graded using the National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 
Summary of overall treatment emergent adverse events will be tabulated. The subject incidence 
of the following TEAEs will be presented: any TEAEs, any TEAEs with worst severity, 
treatment related TEAEs, serious TEAEs, treatment related serious TEAE, ≥grade 3 TEAEs, 
≥grade 3 treatment related TEAEs, ≥grade 3 serious TEAEs, ≥grade 3 serious treatment related 
TEAEs, TEAEs leading to dose interruption, TEAEs leading to dose reduction, TEAEs leading 
to treatment discontinuation, and TEAEs leading to death. 
Following TEAEs will be tabulated by System Organ Class (SOC) and Preferred Term (PT): all 
TEAEs, serious TEAEs, ≥grade 3 TEAEs, treatment related TEAEs, ≥grade 3 treatment related 
TEAEs, and serious treatment related TEAEs. Patient will be counted only once within a SOC 
and PT. 
Following TEAEs will be tabulated by PT: all TEAEs, treatment related TEAEs, serious TEAEs, 
serious treatment related TEAEs, TEAEs leading to dose reduction, treatment related TEAEs 
leading to dose reduction, TEAEs leading to dose interruption, treatment related TEAEs leading 
to dose interruption, TEAEs leading to treatment discontinuation, treatment related TEAEs 
leading to treatment discontinuation, ≥grade 3 TEAEs, ≥grade 3 treatment related TEAEs, CMQ 
bacterial infection, CMQ viral infection, CMQ fungal infection, CMQ cytopenia, SMQ liver 
related investigations, signs and symptoms, SMQ drug related hepatic disorders – comprehensive 
search (narrow), ≥grade 3 CMQ bacterial infection, ≥grade 3 CMQ viral infection, ≥grade 3 
CMQ fungal infection, ≥grade 3 CMQ cytopenia, ≥grade 3 SMQ liver related investigations, 
signs and symptoms, and ≥grade 3 SMQ drug related hepatic disorders – comprehensive search 
(narrow). Patient will be counted only once within a PT. 
Subject listings will be provided for AEs, SAEs, AEs leading to dose interruption, AEs leading 
to dose reduction, AEs leading to treatment discontinuation, and deaths. 
8.5.2. Laboratory Evaluations 


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The summary statistics of all hematology and biochemistry variables and change from baseline 
will be presented for each study assessment.  
For shift tables, laboratory results will be classified using the CTCAE V5.0. All graded 
laboratory parameters will be summarized separately for hematology and biochemistry. 
Corresponding shift tables to compare baseline to the worst post-baseline grade within the 
treatment period will be provided. 
For parameters of hematology and biochemistry, plots of mean / mean change from baseline with 
the corresponding standard error will be displayed. 
Subject listing for hematology, biochemistry and urinalysis will be provided. 
8.5.3. 12 Lead ECG 
Descriptive statistics for ECG parameters at each time point will be presented for the values and 
change from baseline. 
The number and percentage of patients with observed QTcF values that satisfy the following 
conditions will be presented by study visit. The number and percentage of patients with longest 
QTcF values that satisfy the following conditions will be summarized. 
• ≤ 450 msec  
• >450 to ≤ 480 msec 
• >480 to ≤ 500 msec 
• >500 msec 
The number and percentage of patients having change from baseline QTcF values that satisfy the 
following conditions will be presented by study visit. The number and percentage of patients 
with longest change from baseline QTcF values that satisfy the following conditions will be 
summarized. 
• ≤ 0 msec  
• >0 to ≤ 30 msec 
• >30 to ≤ 60 msec 
• > 60 msec 
Subject listing for ECG results will be provided. 
8.5.4. Vital Signs 


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Descriptive statistics for vital signs (weight, BMI, body temperature, respiratory rate, pulse rate, 
systolic and diastolic blood pressure) values and the change from the baseline will be presented 
for each scheduled assessment time point. 
Subject listing for vital signs will be provided. 
8.5.5. Physical Examination 
Clinically significant physical examination findings will be captured as AEs. 
8.6. Pharmacokinetic Analyses 
PK analyses will be presented in a separate PK analysis plan. 
8.7. Other Analyses 
Subgroup Analyses 
Subgroup analyses for the endpoint of ORR will be conducted for the following subgroups： 
• Severe cGVHD at screening (Yes / No) 
• Number of organs involved at baseline (<4 / ≥4) 
• Number of prior lines of therapy (1 / ≥2) 
• Duration of cGVHD before enrollment (by 50th percentile) 
• Lung involvement at baseline (Yes / No) 
• Prior Ruxolitinib (Yes / No) 
• Prior ibrutinib (Yes / No) 
9. References 
NMPA : Statistical Principles for Clinical Trials. 2016 
NMPA : Guidance for Data Management and Statistical Analysis Plan and Report in Clinical 
Trial. 2016