A Single-center, Single-arm, Open-label, Single-dose Phase I Clinical Study to Evaluate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of rhTPO in Healthy Caucasian Participants. Approximately 22 Subjects Will be Enrolled.
Phase: PHASE1
Conditions: Healthy Subjects
Sponsor: 3SBIO AU PTY LTD

Clinical Study Protocol for rhTPO 
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A Single-arm, Open-label, Single-dose, 
Phase I Study to Evaluate the 
Pharmacokinetics, Pharmacodynamics, 
Safety, and Tolerability of Recombinant 
Human Thrombopoietin for Injection 
(rhTPO) in Healthy Caucasian 
Volunteers 
 
Sponsor 
3SBIO AU PTY LTD 
Study Number 
rhTPO-101-AUS 
Version 
2.0 
Version date 
6 Sep 2024  
 
 
Confidentiality statement 
This document contains important confidential business information, which is proprietary to 
3SBIO AU PTY LTD. and shall not be disclosed unless required by current laws or regulations. In 
any case, this confidentiality requirements should be informed to all the people who receive this 
information, they may not be further disclosure of this information. This restriction on disclosure also 
applies to all documents that will be provided in the future and are noted as confidential. 
 
 

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Approved by the Applicant 
Signature of the Sponsor 
 
The undersigned confirms that the following protocol has been agreed and accepted. 
 
 
 
Sponsor Signatory: 
 
Signature:  
 
...................................................................................................... 
 
 
 
Date: ....../....../...... 
Printed Name:  
 
SONG Weifeng, MD  
Director of Medical Department 
 
 
 
 
 

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Principal Investigator Signature Page 
 
 
The undersigned confirms that the following protocol has been agreed upon and accepted and 
that the Principal Investigator agrees to conduct the trial in compliance with the approved 
protocol and will adhere to the principles outlined in ICH Good Clinical Practice (GCP), and 
other regulatory requirements as amended. 
 
I agree to ensure that the confidential information contained in this document will not be used 
for any purpose other than the evaluation or conduct of the clinical investigation without the 
prior written consent of the Sponsor. 
 
 
 
Principal Investigator: 
 
Signature:  
 
................................................................................................ 
 
 
 
Date: ....../....../...... 
Printed Name: 
 
Dr. Sam Francis 
 
 
 
 

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Protocol Amendment Summary 
Document 
Date  
Description of Change 
Original Protocol 
(Version 1.0) 
13 Aug 2024 
NA 
Version 2.0 
6 Sep 2024 
 
Replaced “PD sampling” with “Hematology/PD 
sampling” for clarification in Table 3.  
 
Added “Plateletcrit and platelet distribution width are 
adjunctive pharmacodynamic parameters and they will not 
be reviewed as part of clinical safety laboratory results” in 
Section 1.3 and 8.4.4 because plateletcrit and platelet 
distribution width are not standard haematology 
parameters in Australia. 
 
Added study stopping rules in Section 5.6. 
 
Modified ISR definition in Section 8.4.9. 
 
Modified SAP related description and removed statistical 
analysis report in Section 9.  
 
Modified statistical analysis details in Section 9.  
 
Modified a few wordings, but did not change the original 
intent.  
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ........................................................................................................... 5 
LIST OF FIGURES ................................................................................................................... 7 
LIST OF TABLES ..................................................................................................................... 7 
LIST OF ABBREVIATIONS .................................................................................................... 8 
1 
PROTOCOL SUMMARY .................................................................................... 10 
1.1 
Synopsis ................................................................................................................ 10 
1.2 
Schema .................................................................................................................. 13 
1.3 
Schedule of Activities ........................................................................................... 14 
2 
INTRODUCTION ................................................................................................ 18 
2.1 
Study Rationale ..................................................................................................... 18 
2.2 
Background ........................................................................................................... 18 
2.2.1 
Thrombopoietin and Recombinant Human Thrombopoietin (rhTPO) ................. 18 
2.2.2 
Overview of Nonclinical Studies .......................................................................... 19 
2.2.3 
Overview of Clinical Studies ................................................................................ 19 
3 
OBJECTIVES AND ENDPOINTS ...................................................................... 22 
4 
STUDY DESIGN ................................................................................................. 23 
4.1 
Overall Design ...................................................................................................... 23 
4.2 
Scientific Rationale for Study Design .................................................................. 23 
4.2.1 
Rationale for Study Population ............................................................................. 23 
4.3 
Justification for Dose ............................................................................................ 23 
4.4 
End of Study Definition ........................................................................................ 24 
5 
STUDY POPULATION ....................................................................................... 24 
5.1 
Inclusion Criteria .................................................................................................. 24 
5.2 
Exclusion Criteria ................................................................................................. 25 
5.3 
Lifestyle Considerations ....................................................................................... 26 
5.3.1 
Meals and Dietary Restrictions ............................................................................. 26 
5.3.2 
Activity Restrictions ............................................................................................. 27 
5.3.3 
Contraception requirements .................................................................................. 27 
5.4 
Screen Failures...................................................................................................... 28 
5.5 
Participant Number ............................................................................................... 28 
5.6 
Study Stopping Rules ........................................................................................... 29 
6 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................... 29 
6.1 
Study Intervention(s) Administered ...................................................................... 29 
6.2 
Preparation, Handling, Storage, and Accountability ............................................ 30 
6.3 
Assignment to Study Intervention ........................................................................ 30 
6.4 
Blinding ................................................................................................................ 30 

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6.5 
Study Intervention Compliance ............................................................................ 30 
6.6 
Prior and Concomitant Therapy ............................................................................ 31 
6.6.1 
Prior Therapy ........................................................................................................ 31 
6.6.2 
Concomitant Therapy ........................................................................................... 31 
6.7 
Intervention after the End of the Study................................................................. 32 
7 
PARTICIPANT DISCONTINUATION/WITHDRAWAL.................................... 32 
7.1 
Discontinuation/Withdrawal from the Study ........................................................ 32 
7.2 
Lost to Follow-up ................................................................................................. 33 
8 
STUDY ASSESSMENTS AND PROCEDURES ................................................ 33 
8.1 
General Procedures ............................................................................................... 33 
8.1.1 
Demographic data ................................................................................................. 33 
8.1.2 
Height and weight ................................................................................................. 33 
8.1.3 
Medical History and Prior Therapy ...................................................................... 33 
8.2 
Pharmacokinetics and Immunogenicity ................................................................ 34 
8.3 
Pharmacodynamics ............................................................................................... 34 
8.4 
Safety Assessments ............................................................................................... 34 
8.4.1 
Vital Signs ............................................................................................................. 34 
8.4.2 
Physical Examinations .......................................................................................... 34 
8.4.3 
Electrocardiograms ............................................................................................... 35 
8.4.4 
Clinical Safety Laboratory Tests ........................................................................... 35 
8.4.5 
Virology Test ......................................................................................................... 36 
8.4.6 
Serum or Urine Pregnancy Test ............................................................................ 37 
8.4.7 
Drug Abuse and Alcohol Test ............................................................................... 37 
8.4.8 
Injection site examination ..................................................................................... 37 
8.4.9 
Injection site reaction ............................................................................................ 37 
8.5 
Adverse Events and Serious Adverse Events ....................................................... 38 
8.5.1 
Definitions ............................................................................................................ 38 
8.5.1.1 
Definition of adverse event ................................................................................... 38 
8.5.1.2 
Definition of Serious Adverse Event .................................................................... 38 
8.5.1.3 
Definition of Suspected and Unexpected Serious Adverse Reactions .................. 39 
8.5.2 
Monitoring and Follow-up .................................................................................... 40 
8.5.2.1 
Monitoring ............................................................................................................ 40 
8.5.2.2 
Follow-up .............................................................................................................. 40 
8.5.3 
Adverse Event Recording ..................................................................................... 41 
8.5.4 
Assessment of Adverse Event ............................................................................... 41 
8.5.4.1 
Severity Classification .......................................................................................... 41 
8.5.4.2 
Causality Assessment ........................................................................................... 42 
8.5.5 
Serious Adverse Event Reporting ......................................................................... 43 
8.5.5.1 
Serious Adverse Event Reporting ......................................................................... 43 
8.5.5.2 
Serious Adverse Event Notification...................................................................... 43 
8.5.6 
Pregnancy ............................................................................................................. 43 
8.5.7 
Medication Error ................................................................................................... 44 
8.5.7.1 
Treatment of Overdose ......................................................................................... 44 

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9 
STATISTICAL CONSIDERATIONS ................................................................... 45 
9.1 
Sample Size Determination .................................................................................. 45 
9.2 
Populations for Analyses ...................................................................................... 45 
9.3 
Statistical Analyses ............................................................................................... 46 
9.3.1 
General Considerations ......................................................................................... 46 
9.3.2 
Participant Distribution, Demographics and Baseline Characteristics ................. 46 
9.3.3 
Pharmacokinetic Analysis ..................................................................................... 46 
9.3.4 
Safety Analysis ..................................................................................................... 47 
9.3.5 
Pharmacodynamics Analysis ................................................................................ 48 
9.3.6 
Immunogenicity Analysis ..................................................................................... 48 
9.4 
Data Monitor Committee ...................................................................................... 49 
10 
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL 
CONSIDERATIONS ............................................................................................ 49 
11 
REFERENCES ..................................................................................................... 57 
 
LIST OF FIGURES 
Figure 1 
 Study design and process ........................................................................... 13 
 
LIST OF TABLES 
Table 1 
Schedule of Activities ................................................................................. 14 
Table 2 
Pharmacokinetic blood sampling ................................................................ 16 
Table 3 
Pharmacodynamics and immunogenicity blood sampling .......................... 17 
Table 4 
List of Clinical Studies ................................................................................ 20 
Table 5 
Objectives and Endpoints ............................................................................ 22 
Table 6 
Study drug ................................................................................................... 29 
Table 7 
Laboratory Safety Variables ....................................................................... 36 
Table 8 
Populations for Analysis ............................................................................. 45 
 
 
 

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LIST OF ABBREVIATIONS 
Abbreviation or special term 
Explanation 
ADA 
Anti-Drug Antibody 
AE 
Adverse Event 
ALT 
Alanine Transferase 
AUC 
Area Under the Curve 
AUC0-t 
Area under the serum concentration-time curve from time zero to the 
last measurable serum concentration time t 
AUC0-∞ 
Area under the curve extrapolated from zero to time of infinity 
AUC_%Extrap 
Area ratio under extrapolated concentration-time curve 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BQL 
Below Quantitation Limit 
Cmax 
Peak Concentration 
CHO 
Chinese Hamster Ovary 
CIT 
Chemotherapy-Induced Thrombocytopenia 
CLD-TCP  
Chronic Liver Disease - Thrombocytopenia  
CL/F 
Apparent Clearance 
CRA 
Clinical Research Associate 
CRC 
Clinical Research Coordinator 
CRF 
Clinical Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of Variation 
DBP 
Diastolic Blood Pressure 
DM 
Data Manager 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
FSH 
Follicle Stimulating Hormone  
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HBsAg 
Hepatitis B surface Antigen 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HLA 
Human Leukocyte Antigen 

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Abbreviation or special term 
Explanation 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
INR 
International Normalized Ratio 
IP 
Investigational Product 
ISR 
Injection Site Reaction 
ITP 
Immune Thrombocytopenia 
IUD 
Intrauterine Device 
Ke 
Terminal Elimination Rate Constant 
LLOQ 
Lower Limit of Quantification 
MRT 
Mean Residence Time 
MPV 
Mean Platelet Volume 
NC 
Non-Computable 
ND 
Not Quantifiable 
NQ 
Non-Quantifiable 
rhTPO 
Recombinant Human Thrombopoietin 
PD 
Pharmacodynamic 
PDW 
Platelet Distribution Width 
PK 
Pharmacokinetic 
PLT 
Platelet Count 
QTcF 
Corrected QT Interval (Fridericia) 
RSI 
Reference Safety Information 
RT-PCR 
Real-Time Polymerase Chain Reaction  
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SDV 
Source Data Verification 
SoA 
Schedule of Activities  
SUSAR 
Suspected and Unexpected Serious Adverse Reaction 
t1/2 
Elimination Half-life 
TEAE 
Treatment Emergent Adverse Event 
Tmax 
Time to Peak Drug Concentration 
Vd/F 
Apparent Volume of Distribution 
WOCBP 
Women of Childbearing Potential 

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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A Single-arm, Open-label, Single-dose, Phase I Study to Evaluate the 
Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Recombinant Human 
Thrombopoietin for Injection (rhTPO) in Healthy Caucasian Volunteers 
Rationale: 
Thrombocytopenia is a common clinical problem, with approximately 8 million units of 
platelets transfusions administered each year in the United States to reduce severe bleeding in 
patients. However, this is not an ideal therapy, as at least 30% of patients experience transfusion-
related complications. Repeated platelet transfusions are required in 15 to 25 percent of patients, 
which often lead to HLA-related immune response.  
TPO can significantly stimulate platelet production, increase peripheral blood platelet count, 
and has no significant impacts on platelet morphology and functionality, thus it is an effective 
thrombopoiesis stimulating factor. A large number of studies have shown that recombinant 
human thrombopoietin (rhTPO) can effectively increase the platelet level both in terms of the 
mechanism of action and clinical practice, and has demonstrated a favourable safety profile. 
Recombinant human thrombopoietin (rhTPO, trade name TPIAO®), developed by Shenyang 
Sunshine Pharmaceutical Co., Ltd. (3SBio Inc.), is a full-length glycosylated rhTPO expressed 
in Chinese hamster ovary (CHO) cells and purified via conventional gene recombination 
technology. There are two (2) formulations of rhTPO drug product, namely injection (TPIAO®) 
and lyophilized powder for injection. Both rhTPO formulations are given by subcutaneous 
injection, and they have consistent pharmacokinetic (PK) profile in a single dose PK study of 
cynomolgus monkeys. TPIAO® has been launched in China for chemotherapy-induced 
thrombocytopenia (CIT) in 2005 and for adult immune thrombocytopenia (ITP) in2010. It was 
further approved in 2024 for the treatment of pediatric ITP in children over six years old. In 
addition, TPIAO® has been approved for marketing in the nine other countries, including 
Thailand, Philippines, Sri Lanka, Cambodia, Dominica, Paraguay, Costa Rica, Uzbekistan and 
Ukraine. Completed clinical trials have demonstrated that rhTPO could significantly increase 
platelet levels in patients with CIT and ITP, with mild adverse reactions and favourable safety. 
This study is designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and 
safety profile of rhTPO in healthy Caucasian volunteers.  
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary  

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Objectives 
Endpoints 
To evaluate the PK profile following a single dose 
of rhTPO in healthy Caucasian  
PK concentration-time profile and PK parameters: 
Tmax, Cmax, t1/2, MRT, AUC0-t, AUC0-∞, Vd/F, Ke, 
CL/F, AUC_%Extrap 
Secondary  
To evaluate the PD profile following a single dose 
of rhTPO in healthy Caucasian 
PLT counts and changes in PLT over time. 
To evaluate the safety and tolerability following a 
single dose of rhTPO in healthy Caucasian 
Incidence and severity of AEs and SAEs, physical 
examination, vital sign, clinical laboratory test, 
ECG, ISR  
To evaluate the immunogenicity profile following 
a single dose of rhTPO in healthy Caucasian 
Incidence of the development of ADAs and NAb 
(if applicable) to rhTPO.   
Overall Design: 
This is a single-center, single-arm, open-label, single-dose phase I clinical study to evaluate 
pharmacokinetics, pharmacodynamics, safety and tolerability of Recombinant Human 
Thrombopoietin for Injection (rhTPO) in healthy Caucasian participants. Approximately 22 
healthy Caucasian participants will be enrolled for this study. 
One dose level is planned in this study, and participants will receive a single abdominal 
subcutaneous injection at a dose of 300U/kg after entering the study. 
Participants will undergo screening, admission (baseline), administration and follow-up 
observation period. Participants will sign an informed consent form before any study procedures 
are performed. During screening, all participants will be screened for study eligibility within 28 
days prior to administration. Eligible participants will be admitted to the clinical study ward no 
later than one day prior to dosing (D-1). Participants need to fast for at least 10 hours prior to 
dosing and 4 hours after dosing. Single abdominal subcutaneous injection of the study drug will 
be given on D1. The administration and follow-up observation period will be 29 days (D1~D29). 
Participants may be discharged at D7 at the judgment of the investigator. PK blood samples will 
be collected from D-1 to D14, tolerance and safety will be observed from D1 to D29, and blood 
samples for PD and anti-drug antibody (ADA) will be collected from screening to D29. After 
completion of relevant assessments on D29, participants will be considered as having completed 
this study.  
Design of PK study 
PK study is required for all participants in this study. PK blood samples will be collected at the 
following specified time points: D-1, before administration (D1), 2 h, 5 h, 8 h, 10 h, 12 h, 16 h, 
24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 216 h, 264 h and 312 h after administration. 
Design of PD study 

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PD blood samples will be collected from participants in this study at specified time points: D-
28 ~ D-2, D-1, D4, D8, D10, D14, D22 and D29; PD blood samples will be collected in the 
early morning for hematology, in which platelet count will be taken as PD indicator. 
Design of immunogenicity study 
Immunogenicity blood samples will be collected from participants in this study at specified time 
points: D-1, D14, and D29. Samples may be further characterized to determine the titer and the 
presence of neutralizing antibodies (NAb) if positive for ADA. 
Data Monitoring / Other Committee: No 
Statistical methods: 
Unless otherwise specified, all statistical analyses will be performed using SAS 9.4 software (or 
above). In general, continuous variables will be described statistically using number of cases, 
mean, standard deviation, median, quartile, minimum, and maximum etc; categorical and rank 
variables will be described statistically using frequencies and percentages for each category or 
rank; missing values will not be included in the calculation of percentages unless otherwise 
specified. This is a Phase I exploratory clinical study of single-arm, single-dose administration. 
Descriptive statistical analysis will be mainly used without statistical inferences. 
Demographic data and other baseline characteristics 
Demographic data and other baseline characteristics will be summarized using descriptive 
statistics. 
PK parameter analysis 
Pharmacokinetic parameters will be calculated using Phoenix WinNonlin 7.0 software (or above) 
for fitting with noncompartmental analysis. The following pharmacokinetic parameters will be 
calculated based on the Pharmacokinetics Parameter Sets (PKPS): time to peak drug 
concentration (Tmax), peak concentration (Cmax), mean residence time (MRT), terminal 
elimination rate constant (Ke), area under serum concentration-time curve (AUC), apparent 
clearance (CL/F), apparent volume of distribution (Vd/F), elimination half-life (t1/2), area ratio 
under extrapolated concentration-time curve (AUC_% Extrap), etc. Descriptive statistics will be 
performed for pharmacokinetic parameters, such as number of observations, arithmetic mean, 
standard deviation, coefficient of variation (CV%), median, quartiles (Q1 and Q3), minimum, 
maximum, geometric mean, geometric standard deviation and geometric CV%. For Tmax, only 
the number of observations, median, minimum, and maximum will be listed.  
PD indicator analysis 
All analyses of pharmacodynamics will be based on the Pharmacodynamic Analysis Set (PDS). 

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Platelet count (PLT) at each time point and its change from baseline will be statistically 
described, and the number of observations, mean, standard deviation, coefficient of variation, 
median, quartiles (Q1 and Q3), minimum and maximum will be provided. Maximum platelet 
count change from baseline (Emax) and time to peak platelet count (ETmax) will be calculated , 
and descriptive statistics will be performed. In addition, ET max will be only presented as median, 
minimum and maximum values. A line graph with mean and SD will be generated. Line plots 
of the changes in platelet count by visit for each participant will also be displayed. 
Immunogenicity Analysis 
ADAS will be used to summarize the immunogenicity data of the participants at different time 
points. According to the planned timepoints, the number and percentage of ADA positive will 
be summarized and listed. If possible, the titers and NAb for ADA-positive will be further 
analyzed and summarized. 
Safety and tolerability analysis 
The analysis of safety data (adverse event [AE], treatment emergent adverse event [TEAE], 
serious adverse event [SAE], clinical laboratory parameters, electrocardiogram [ECG] 
parameters, vital signs, and physical examinations) will be descriptive and performed on the 
safety population. The adverse events incidence, overall and per Common Terminology Criteria 
for Adverse Events (CTCAE) grade, will be presented. The attribution to the test drugs, time-
of-onset, duration of the event, its resolution, and any concomitant medications administered 
will be reported. 
1.2 
Schema 
 
Figure 1 
 Study design and process 
 

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1.3 
Schedule of Activities 
The procedures for this study are presented in the schedule of activities (SoA) (Table 1). 
Table 1 
Schedule of Activities 
Item 
Screening  Baseline Administration 
Follow-up observation period 
D-28~D-2 
D-1 
D1 
D2~D6 
D7 
D8 
D10 
D12 
D14 
D22 
D29/Early 
withdrawal 
Visit Window 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
±2d 
±2d 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Demographic information1 
X 
 
 
 
 
 
 
 
 
 
 
Prior therapy2 
X 
X 
 
 
 
 
 
 
 
 
 
Smoking history 
X 
 
 
 
 
 
 
 
 
 
 
Medical history3 
X 
X 
 
 
 
 
 
 
 
 
 
Single dose administration 
 
 
X 
 
 
 
 
 
 
 
 
Admission 
 
X 
 
 
 
 
 
 
 
 
 
Discharge4 
 
 
 
 
X 
 
 
 
 
 
 
Safety Assessments 
Injection site examination 
 
X 
 
 
 
 
 
 
 
 
 
Injection site reaction 
 
 
X5 
X (D2, D3) 
X 
 
 
 
X 
 
X 
Physical examination6 
X 
X 
 
X (D4 only) 
 
X 
 
 
 
 
X 
Height, weight, body mass 
index 
X 
X7 
 
 
 
 
 
 
 
 
 
Vital signs8,17 
X 
X 
X8 
X (daily) 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG9,17 
X 
X 
X9  
 
 
 
 
 
X 
 
X 
Adverse events10 
X 
X 
Concomitant 
medication/therapy 
X 
 
X 
Laboratory Assessments11,17  

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Item 
Screening  Baseline Administration 
Follow-up observation period 
D-28~D-2 
D-1 
D1 
D2~D6 
D7 
D8 
D10 
D12 
D14 
D22 
D29/Early 
withdrawal 
Visit Window 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
/ 
±2d 
±2d 
Hematology/PD blood 
collection12 
X 
X 
 
X (see Table 3) 
 
X 
X 
X 
Urinalysis12 
X 
X 
 
 
 
 
 
 
 
 
X 
Clinical chemistry12 
X 
X 
 
X (D4 only) 
 
X 
 
 
X 
X 
X 
Coagulation12 
X 
X 
 
X (D4 only) 
 
X 
 
 
X 
X 
X 
Serum virology test13 
X 
 
 
 
 
 
 
 
 
 
 
RT-PCR test for 
COVID-1914 
X 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test15 
X 
X 
 
 
 
 
 
 
 
 
X 
Drug Abuse and Alcohol 
Testing16 
X 
X 
 
 
 
 
 
 
 
 
 
PK sample collection 
 
X 
X (see Table 2) 
 
 
ADA sample collection 
 
X 
 
 
 
 
 
 
X 
 
X 
Notes: 
1 
Demographic data will include age or year of birth, gender, and race/ethnicity. 
2 
Prior therapy includes medications used by the participant within 28 days prior to study drug administration. 
3 
Medical history related to the inclusion and exclusion criteria, other medical history of clinically significant disease starting within 3 months before signing 
the ICF, surgery history, reproductive status (i.e., no childbearing potential or childbearing potential), and allergy history will be collected. 
4 
Participant s may be discharged at D7 at the judgment of the investigator. 
5 
For D1, injection site assessment (ISR) will be performed at pre-dose, 0.5h, 1h±10min, 3h±15min, 6h±15min, 9h±15min, 12h±15min post-dose. 
6 
A complete physical examination will be performed and include assessments of the following; general appearance, respiratory, cardiovascular, abdomen, 
skin, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal (including spine and extremities), urogenital, 
dermatological, gastrointestinal, endocrine, hematologic/lymphatic, and neurological systems. 
7 
Weight only will be tested at D-1. 
8 
Vital signs include systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body temperature, and respiratory rate, see section 8.4.1. For D1, 
vital signs will be performed at pre-dose, 6h±15min, 12h±15min post-dose. Allow a single repeat for vital signs at screening or baseline per the Investigator’s 
discretion for the purpose of further determining eligibility. 
9 
Allow a single repeat for ECG at screening or baseline per the Investigator’s discretion for the purpose of further determining eligibility. See section 8.4.3. 
ECG on D1 will be performed at 10 h ± 15 min post-dose (before blood sample collection). 

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10 
Adverse medical events occurring after the participant has signed the ICF and prior to the first dose are recorded in the eCRF as history/concomitant 
illnesses and are not recorded as AEs unless one of the following is met: injury/damage resulting from the operation of any clinical laboratory test (AEs 
related to study operating procedures); AEs resulting from discontinuation of medication related to the study protocol; AEs meet SAE severity criteria. 
11 
Any abnormal laboratory parameter(s) results outside of the reference range at screening or baseline may be repeated once per the Investigator’s discretion 
for the purpose of further determining eligibility. Plateletcrit and platelet distribution width are adjunctive pharmacodynamic parameters and they will not 
be reviewed as part of clinical safety laboratory results. 
12 
Unscheduled blood sample is required as soon as possible for hematology in the presence of venous thrombosis. Additional samples may be collected if 
clinically significantly abnormal at the discretion of the investigator. Participants will abstain from all food at least 8 h prior to any safety laboratory 
evaluations (minimum of 12 h for lipid profile at screening). 
13 
Serum virology tests include: 
- 
HBsAg, HBsAb, HBeAg, HBeAb, HBcAb 
- 
HCV antibody (In the case of positive HCV antibody, the test of HCV RNA will be followed)  
- 
HIV antibody 
- 
Syphilis (treponema pallidum particle assay, TPPA) 
14 
Nasopharyngeal or oropharyngeal swab will be collected for Coronavirus Disease 2019 (COVID-19) real-time reverse transcription polymerase chain 
reaction (RT-PCR) test.  
15 
Pregnancy test on urine or blood sample will be performed for female Participants of childbearing potential (see section 5.3.3). The serum pregnancy test will 
be performed at the screening visit, and the urine pregnancy test will be performed on Day-1 and afterwards. A serum pregnancy test must be performed if 
the urine pregnancy test is positive or equivocal.  
16 
Urine drug test includes at minimum: Amphetamines (AMP), Methamphetamines (MET), Methadone (MTD), Barbiturates (BAR), Benzodiazepines 
(BZO), Cocaine (COC), Opiates (OPI), Methyl enedioxy methamphetamine (MDMA), Phencyclidine (PCP), Tetrahydrocannabinol (THC). Allow a single 
repeat for drug of abuse urine test in the event of a false positive.  
17 
If assessments are scheduled at the same time, the order will be ECG > Vital signs> bloods sample.  
 
Table 2 
Pharmacokinetic blood sampling 
Study day 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D10 
D12 
D14 
Hours post 
start time of 
administrati
on  
Pre-
dose 
Pre-
dose 
2 
5 
8 
10 
12 
16 
24 
36 
48 
72 
96 
120 
144 
168 
216 
264 
312 
Window 
Period 
/ 
/ 
±10min 
±15 min 
±1 h 
±2 h  
±8 h 
☆PK  
sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Note: For PK sample marked with "☆", the samples should be sent to a third-party testing organization for testing. 
Table 3 
Pharmacodynamics and immunogenicity blood sampling 
Study day 
D-28~-2 
D-1 
D4 
D8 
D10 
D14 
D22 
D29 
Window Period 
/ 
/ 
/ 
/ 
/ 
/ 
±2d 
±2d 
Hematology/PD 
sampling 
X 
X 
X 
X 
X 
X 
X 
X 
☆ADA sampling 
 
X 
 
 
 
X 
 
X 
Note:  
a. 
For ADA sample marked with "☆", the samples should be sent to a third-party testing organization for testing. Samples may be further characterized to 
determine the titer and the presence of neutralizing antibodies (NAb) if positive for ADA. 
b. 
All PD samples will be collected in the early morning  for hematology test, in which platelet count will be used as an index of PD. 
 

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2 
INTRODUCTION 
2.1 
Study Rationale 
Thrombocytopenia is a common clinical problem, with approximately 8 million units of 
platelets transfusions administered each year in the United States to reduce severe bleeding in 
patients. However, this is not an ideal therapy, as at least 30% of patients experience 
transfusion-related complications. Repeated platelet transfusions are required in 15 to 25 
percent of patients, which often lead to human leukocyte antigen (HLA)-related immune 
response. TPO can significantly stimulate platelet production, increase peripheral blood platelet 
count, and has no significant impacts on platelet morphology and functionality, thus it is an 
effective thrombopoiesis stimulating factor. A large number of studies have shown that 
recombinant human thrombopoietin (rhTPO) can effectively increase the platelet level both in 
terms of the mechanism of action and clinical practice, and has demonstrated a favourable safety 
profile. 
Recombinant human thrombopoietin (rhTPO, trade name: TPIAO®), developed by Shenyang 
Sunshine Pharmaceutical Co., Ltd. (3SBio Inc.), is a full-length glycosylated rhTPO expressed 
in Chinese hamster ovary (CHO) cells and purified via conventional gene recombination 
technology. There are two (2) formulations of rhTPO drug product, namely injection (TPIAO®) 
and lyophilized powder for injection. Both rhTPO formulations are given by subcutaneous 
injection, and they have basically consistent pharmacokinetic (PK) profile in a single dose PK 
study of cynomolgus monkeys. TPIAO® has been launched in China for chemotherapy-induced 
thrombocytopenia (CIT) in 2005 and for adult immune thrombocytopenia (ITP) in 2010. It was 
further approved in 2024 for the treatment of pediatric ITP in children over six years old. In 
addition, TPIAO® has been approved for marketing in the nine other countries, including 
Thailand, Philippines, Sri Lanka, Cambodia, Dominica, Paraguay, Costa Rica, Uzbekistan and 
Ukraine. Completed clinical trials have demonstrated that rhTPO could significantly increase 
platelet levels in patients with CIT and ITP, with mild adverse reactions and favourable safety. 
This study is designed to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) and safety 
profile of rhTPO in healthy Caucasian volunteers.  
2.2 
Background 
2.2.1 
Thrombopoietin and Recombinant Human Thrombopoietin (rhTPO) 
Thrombopoietin (TPO) is an endogenous cytokine that stimulates the growth and differentiation 
of megakaryocytes, mainly produced by the liver, and produces biological effects by binding to 
its specific receptor c-mpl, i.e., it regulates megakaryocyte proliferation, differentiation, 
maturation, and splitting to form functional platelets. In vivo tests have shown that TPO can 
significantly stimulate platelet production and increase platelet count in peripheral blood[1][2][3] . 
TPO also acts on early stem cells and expands the pool of targeted megakaryotic progenitor 

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cells[4] . TPO also works synergistically with erythropoietin, stem cell factor, interleukin-3, 
granulocyte colony-stimulating factor, etc., to promote proliferation of erythroid and 
granulocytic progenitor cells, and to facilitate the entry of stem cells into the proliferative 
cycle[5]. 
Recombinant human thrombopoietin, developed by 3SBio Inc., is a full-length glycosylated 
TPO expressed in CHO cells and purified, with a half-life of approximately 40 hours. rhTPO, 
which has a similar platelet-raising pharmacology to endogenous thrombopoietin, was approved 
for the treatment of CIT for solid tumors in 2005, and gained a second indication for the 
treatment of adult ITP in 2010. It was further approved in 2024 for the treatment of pediatric 
ITP in children over six years old. In addition, TPIAO® has been approved for marketing in the 
9 other countries.  
2.2.2 
Overview of Nonclinical Studies 
Nonclinical studies have indicated that rhTPO exhibited pharmacological effects of increasing 
platelets like endogenous TPO: rhTPO stimulated the proliferation and differentiation of bone 
marrow megakaryocytic cell lines and promoted the recovery of peripheral blood platelets. In 
terms of toxicology and safety pharmacology, rhTPO was well tolerated and had no influence 
on the nervous system, cardiovascular and respiratory systems of animal model after 
administration. 
2.2.3 
Overview of Clinical Studies 
A total of 14 clinical studies sponsored by 3SBio Inc. were conducted, including 7 Phase I 
clinical studies, 1 Phase II clinical study, 4 Phase III clinical studies and 2 Phase IV clinical 
studies (Table 4). 
Currently, numerous clinical studies have shown that rhTPO was effective in increasing platelet 
levels in ITP patients and demonstrated favorable effects in CIT patients with solid tumors, 
including increasing platelet count, shortening the duration of thrombocytopenia, and reducing 
the need for platelet transfusions. For patients with CLD-TCP undergoing invasive surgery, 
rhTPO represented a potential alternative to platelet transfusion. 
Completed clinical studies have shown that the overall incidence of adverse reactions in healthy 
subjects, CIT patients and ITP patients is low and mild, and most of them do not require special 
treatment and improve on their own, with no obvious effects on liver and kidney function, 
coagulation system and hematology, demonstrating a good safety profile of rhTPO. 
See more detailed information in the Investigator’s Brochure. 

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Table 4 
List of Clinical Studies 
Study 
No. 
Study 
phase 
Study design 
Dosage and 
administration 
Sample 
size 
Target 
population 
Duration 
of 
treatmen
t 
001 
I 
Self-controlled 0.25, 0.5, 1.0, 2.0μg/kg; s.c 27 
Healthy subjects 
Up to 14 
days 
002 
I 
Self-controlled 1.0μg/kg; q.d.s.c 
7 
CIT patients 
receiving 
chemotherapy 
7-14 days 
003 
I 
Pharmacokinet
ic study 
0.5, 1, 2 μg/kg; s.c 
24 
Healthy subjects 
Single 
dose 
004 
I 
Pharmacokinet
ic study 
1.0 μg/kg; q.d × 14 doses or 
q.o.d × 7 doses  
8 
Patients with 
malignancy, ITP 
or aplastic anemia 
7 or 14 
days 
005 
Ia 
Single dose 
pharmacokinet
ic study 
Cohort A: 300 U/kg 
Cohort B: 300 U/kg 
Cohort C: 150 U/kg, 300 
U/kg, 450 U/kg 
A:10 
B:12 
C:0 
Patients with 
hepatic 
impairment 
Single 
dose 
006 
Ia 
Single dose 
pharmacokinet
ic study 
300U/kg 
10 
Healthy 
volunteers 
Single 
dose 
007 
Ib 
Multiple-dose 
pharmacokinet
ic study 
Fixed dose 15000U once 
daily 
54  
Patients with 
hepatic 
impairment 
7 days 
008 
II 
Randomized 
crossover self-
controlled 
1.0μg/kg; q.d., s.c 
62 
CIT patients 
receiving 
chemotherapy 
14 days 
009 
III 
Randomized, 
crossover, self-
controlled; 
non-
randomized, 
self-controlled; 
uncontrolled, 
open-label 
1.0μg/kg; q.d., s.c 
229 
CIT patients 
receiving 
chemotherapy 
14 days 
82 
ITP patients 
010 
III 
Multicenter, 
randomized, 
open-label, 
blank 
controlled 
1.0μg/kg; q.d., s.c 
140 
ITP patients 
refractory to 
glucocorticoids 
14 days 

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011 
III 
Open-label, 
randomized, 
crossover, self-
blank 
controlled 
1.0μg/kg; q.d., s.c 
59 
Patients with CIT 14 days 
012 
IV 
Open-label, 
multicenter 
post-marketing 
non-
interventional 
clinical study 
300U/kg; q.d., s.c 
2000 
planned, 
1153 
currently 
enrolled 
CIT Patients for 
solid tumors 
≤ 14 days 
013 
IV 
Ongoing 
ITP patients 
014 
III 
Multi center, 
randomized, 
double-blind, 
parallel, 
placebo-
controlled 
clinical study 
Fixed dose 15000U once 
daily 
120 
Patients with 
chronic liver 
disease-related 
thrombocytopenia 
(CLDT) 
≤ 5 days 
or 7 days 
 

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3 
OBJECTIVES AND ENDPOINTS 
Table 5 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary  
To evaluate the PK profile following a single dose 
of rhTPO in healthy Caucasian  
PK concentration-time profile and PK parameters: 
Tmax, Cmax, t1/2, MRT, AUC0-t, AUC0-∞, Vd/F, Ke, 
CL/F, AUC_%Extrap. 
Secondary  
To evaluate the PD profile following a single dose 
of rhTPO in healthy Caucasian 
PLT counts and changes in PLT over time. 
To evaluate the safety and tolerability following a 
single dose of rhTPO in healthy Caucasian 
Incidence and severity of AEs and SAEs, physical 
examination, vital sign, clinical laboratory test, 
ECG, ISR  
To evaluate the immunogenicity profile following 
a single dose of rhTPO in healthy Caucasian 
Incidence of the development of ADAs and NAb 
(if applicable) to rhTPO  

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4 
STUDY DESIGN 
4.1 
Overall Design 
This is a single-center, single-arm, open-label, single-dose phase I clinical study to evaluate 
pharmacokinetics, pharmacodynamics, safety and tolerability of Recombinant Human 
Thrombopoietin for Injection (rhTPO) in healthy Caucasian volunteers. Approximately 22 
healthy Caucasian participants will be enrolled for this study. 
One dose level is planned in this study, and participants will receive a single abdominal 
subcutaneous injection at a dose of 300U/kg after entering the study. 
Participants will undergo screening, admission (baseline), administration and follow-up 
observation period. Participants will sign an informed consent form before any study procedures 
are performed. During screening, all participants will be screened for study eligibility within 28 
days prior to administration. Eligible participants will be admitted to the clinical study ward no 
later than one day prior to dosing (D-1).  Participants need to fast for at least 10 hours prior to 
dosing and 4 hours after dosing. Single abdominal subcutaneous injection of the study drug will 
be given on Day 1 (D1). The administration and follow-up observation period will be 29 days 
(D1~D29). Participants may be discharged at D7 at the judgment of the investigator. PK blood 
samples will be collected from D-1 to D14, tolerance and safety will be observed from D1 to 
D29, and blood samples for PD and ADA will be collected from screening to D29. After 
completion of relevant assessments on D29, participants will be considered as having completed  
this study. 
4.2 
Scientific Rationale for Study Design 
4.2.1 
Rationale for Study Population 
As the PK, PD, and safety profile of rhTPO in Caucasian populations have not been determined, 
the target population for this study is healthy participants from the Caucasian population. The 
data obtained from this healthy Caucasian participant study could provide theoretical support 
for the subsequent bridging data from domestic and international clinical studies. 
4.3 
Justification for Dose 
In a single subcutaneous injection of rhTPO (0.25 μg/kg ~ 2.0 μg/kg) in Chinese healthy 
subjects conducted by the sponsor in 2001, a total of 27 subjects were enrolled in the study. The 
results showed that: only one subject's body temperature rose to 37.4℃ 6 hours after the 
administration of rhTPO, and then fell back to normal 2 hours later; one subject experienced 
mild fatigue, poor appetite and drowsiness on the second day after the administration of rhTPO; 
no other uncomfortable reactions or abnormal signs were observed during the period of 
observation. In addition, in this study, 21 days after single subcutaneous administration of 
rhTPO, there were no significant changes in peripheral blood  red blood cell and  haemoglobin, 

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and no significant changes in white blood cell counts and classifications; platelet counts 
increased dose-dependently, and platelet counts increased gradually after administration of 
rhTPO, reaching a peak on the 10th to 14th day after administration of rhTPO.  The PLT counts 
of the rhTPO 2.0 μg/kg group increased from (209±40) × 109/L to (317±54) × 109/L on 14th 
day after administration of rhTPO, and decreased to (262±64) × 109/L on 21st day after 
administration of rhTPO. There were no significant changes in mean platelet volume (MPV) 
and platelet distribution width (PDW) before and after the administration of rhTPO 2.0 μg/kg 
in the study. 
In the single subcutaneous injection of rhTPO (300 U/kg) tolerance study in healthy Chinese 
subjects conducted in 2020, a total of 10 subjects were enrolled, and the results showed that: a 
total of 7 (70%) subjects experienced treatment emergent adverse event (TEAE), and all of the 
TEAEs were grade 1; 3 (30%) subjects experienced TEAE related to the investigational drug, 
and no medical intervention was given, and all of them recovered to normal by the completion 
date of the study. No serious adverse even (SAEs) and no TEAEs leading to withdrawal from 
the study occurred in this study. 
Taken together, the above information suggests that rhTPO is expected to be safe for a single 
subcutaneous injection of 300U/kg (about 1.0 μg/kg) in healthy participants. 
4.4 
End of Study Definition 
End of study (End of trial): The end of the study is defined as the date of the last visit of the 
last participant in the study. 
End of Study (Individual participant): A participant who has completed all phases of the 
study will be considered to have completed this study. 
5 
STUDY POPULATION 
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Healthy Caucasian adult male and female participants aged 18-50 years (inclusive) at the 
time of informed consent. Caucasian is defined as of European, Middle Eastern, or North 
African descent. 
2. Male participants weighing no less than 50 kg. Female participants should not weigh less 
than 45 kg. 
3.  Body mass index (BMI) within the range 18.0 to 32.0 kg/m2 (inclusive). 
Note: BMI = weight [kg] / (height [m])2 

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4. Participants are in good general health as determined by the investigator, based on a medical 
evaluation including medical history, vital signs, physical examination, 12-lead 
electrocardiogram, clinical safety laboratory tests;  
Note: Any results outside of the reference range at screening or baseline may be repeated 
once per the Investigator’s discretion for the purpose of further determining eligibility. 
5. Platelet counts must be within the normal range; measurements can repeat once for 
verification, if necessary. 
6.  Women of childbearing potential (WOCBP, see section 5.3.3) must have a negative serum 
or urine pregnancy test prior to the start of study drug and must not be breastfeeding, 
lactating or planning pregnancy during the study period. WOCBP who are not exclusively 
in same-sex relationships and males with partners of child-bearing potential must agree to 
use adequate contraception from signing the informed consent until 3 months after 
completion of the study. In addition, females must not donate ova (eggs) and males must 
not donate sperm from signing the informed consent until 3 months after completion of the 
study; 
7. Negative for COVID-19 based on the nasopharyngeal or oropharyngeal swab with the 
method of real-time reverse transcription-polymerase chain reaction (RT-PCR) at 
Screening and Day-1.  
8. Volunteer to participate in this study, be able to understand and comply with the clinical 
study protocol requirements, and sign the informed consent form in writing. 
5.2 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
1 History of  hypersensitivity to components of  study drug or analogs; history of anaphylaxis 
or other significant allergy in opinion of the investigators. 
2 Known allergy to heparin or history of heparin-induced thrombocytopenia; 
3 Received a platelet transfusion within 2 weeks or platelet-boosting medication within 4 
weeks prior to  dosing; 
4 History of hospitalization or surgical procedure within 3 months prior to dosing, or bleeding 
from trauma or internal bleeding greater than 100 mL, or donating more than 100 mL of 
blood; 
5 History or presence of autoimmune disease, malignancy, thromboembolic disease, bleeding 
disorders, cardiovascular, hepatic, renal, muscular, hematopoietic, respiratory, neurological, 
or psychiatric disorders capable of significantly altering the absorption, metabolism, or 
elimination of drugs, constituting a risk to the participant when taking the study drug; or 
interfering with the interpretation of data judged by the investigator;  
Note: Uncomplicated cholecystectomy and appendectomy are permitted; History of fully 
resolved childhood asthma is not permitted. 

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6 History or presence of chronic diseases such as hypertension and diabetes (including type 1 
and type 2 diabetes); 
7 History of malignancy with the exception of successfully treated basal cell or squamous cell 
skin cancer with no evidence of recurrence for 5 years. 
8 History of platelet clumping that prevents reliable measurement of platelet counts; 
9 Positive for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibody and 
Human Immunodeficiency Virus (HIV) antibody, Syphilis antibody; 
Note: Participants with positive hepatitis C antibody can be enrolled if a confirmatory 
negative hepatitis C RNA test is obtained. 
10 Immunization with a COVID-19 vaccine 14 days prior to dosing or planned vaccination 
within 30 days after dosing 
11 Use of prescription medication within 14 days prior to dosing and 7 days prior to dosing for 
over the counter medication/vitamins/herbal supplements (with the exception of 
contraception, occasional paracetamol < 2g/day, and standard dose of multivitamins).  
12 Consuption of alcohol, caffeinated products (coffee, tea, cola, chocolate), grapefruit fruits, 
or products containing grapefruit within 48 hours prior to dosing; 
13 Consuption of any poppy seeds (e.g., orange and poppy seed muffin, poppy seed bread) 
within 48 hours prior to screening and admission. 
14 History of drug abuse within 2 years prior to dosing; or positive alcohol/urine drug screen 
prior to dosing; Regular alcohol consumption within 6 months prior to dosing, i.e., on 
average more than 14 units of alcohol per week (1 unit = 360mL of beer or 45mL of spirits 
at 40% alcohol by volume or 150mL of wine); 
15 Use of tobacco or nicotine products equivalent to more than 2 cigarettes a day on average 
within 3 months prior to dosing; 
16 Have special dietary requirements and are unable to comply with the diet offered and the 
corresponding regulations; 
17 Pregnant or breastfeeding female, or positive pregnancy test;  
18 Individuals who cannot tolerate venipuncture or who suffer from needle and bloodsickness; 
19 Participation in another clinical study of investigational drug within 3 months prior to dosing; 
20 Other participants judged by the investigator to be unsuitable for participation. 
5.3 
Lifestyle Considerations 
5.3.1 
Meals and Dietary Restrictions 
Participants will be admitted to the site the day before dosing (D-1) and will be uniformly fed a 
standard meal.  
Participants will abstain from alcohol, tobacco- or nicotine-containing products, caffeine- or 
xanthine-containing products (e.g., coffee, tea, cola, chocolate, etc), grapefruit-containing 

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products for 48 h prior to dosing and until collection of the final PK sample, as well as 24 h 
prior to subsequent outpatient visits. 
Participants will abstain from any poppy seeds (e.g., orange and poppy seed muffin, poppy seed 
bread) within 48 hours prior to screening and admission. 
Participants will abstain from all food at least 8 h prior to any safety laboratory evaluations 
(minimum of 12 h for lipid profile at screening). 
5.3.2 
Activity Restrictions 
Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, calisthenics, 
aerobics) for at least 48 hours prior to each blood collection for clinical laboratory tests. Walking 
at a normal pace will be permitted. 
5.3.3 
Contraception requirements 
WOCBP are defined as any female who has experienced menarche and who has not undergone 
surgical sterilization (hysterectomy or bilateral oophorectomy) at least 6 weeks before screening 
and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in the absence 
of other biological causes. In addition, females under the age of 55 years must have a 
documented serum follicle stimulating hormone (FSH) level > 40mIU/mL to confirm 
menopause. Male participants with potentially postmenopausal partners who are under the age 
of 55 years must use condoms unless their partner’s postmenopausal status has been confirmed 
by FSH level. 
WOCBP who are not exclusively in same-sex relationships and males with partners of child-
bearing potential must use adequate contraception from signing the informed consent until 3 
months after completion of the study. In addition, females must not donate ova (eggs) and males 
must not donate sperm from signing the informed consent until 3 months after completion of 
the study. 
Males and WOCBP who are continuously not heterosexually active are exempt from 
contraceptive requirements. However, WOCBP must still undergo pregnancy testing as per 
protocol.  
Investigators will counsel WOCBP and male participants who are sexually active with WOCBP 
on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators will advise on the use of an adequate methods of contraception, which is defined 
as use of a condom by the male partner combined with use of a highly effective method of 
contraception by the female partner. A highly effective method of contraception is one that has 
a failure rate of < 1% when used consistently and correctly. Male participants must inform their 
female partners who are WOCBP of the contraceptive requirements of the protocol and are 
expected to adhere to using contraception with their partner. 

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Highly effective methods of contraception are listed below:  
− 
Hormonal methods of contraception including oral contraceptives containing 
combined estrogen and progesterone, a vaginal ring, injectable and implantable 
hormonal contraceptives, intrauterine hormone-releasing system (e.g. Mirena) and 
progestogen-only hormonal contraception associated with inhibition of ovulation  
− 
Nonhormonal intrauterine device (IUD)  
− 
Bilateral tubal occlusion  
− 
Vasectomised participant/partner with documented azoospermia 90 days after 
procedure, if that partner is the sole sexual partner.  
For female participants, contraception (required to be a highly effective method as described 
above) should begin at least 1 month prior to screening to ensure contraceptive is in full effect. 
Complete abstinence, defined as the complete avoidance of heterosexual intercourse - is an 
acceptable form of contraception if used consistently throughout the duration of study and for 
the durations after dosing specified for males and females above. It is not necessary to use any 
other method of contraception when complete abstinence is elected. WOCBP who choose 
complete abstinence must continue to have pregnancy tests as per protocol. The reliability of 
sexual abstinence needs to be evaluated by the Investigator in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the participant. 
5.4 
Screen Failures 
For participants who provide informed consent and subsequently do not meet eligibility criteria 
or withdraw consent before the single dose of study drug is administered, study site personnel 
should document the screen failure in the participant’s source documents. A minimum set of 
screen failure information is required to be entered into the Electronic Data Capture (EDC) 
Systems, including demographics, screen failure details (e.g., failed eligibility criteria), any AEs, 
any SAEs and any related concomitant medications that occurred during the Screening Period. 
Participants who do not meet the criteria for participation in this study (ie, screen failures) may 
be rescreened once. Rescreened participants will be re-consented and assigned a new screening 
number. All screening assessments must be repeated during re-screening unless some screening 
assessments are considered valid by the investigator. 
5.5 
Participant Number 
Participants will be given a screening number after signing the informed consent form, which 
consists of S + three Arabic numerals, with the 1st screened participant having a screening 
number of S001, and so on. 
Participants who were screened and qualified for entry into this study will be given an enrolment 

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number, which consists of R + three Arabic numerals, starting with R001, and assigned to 
participants in the order of screening. 
When a participant is replaced, the enrolment number of the replacement participant will be 
increased by "100" to distinguish it from other participants. For example, if the dislodged 
participant's entry number is "R006", the replacement participant's entry number is "R106". If 
the replacement participant is dislodged again, add an additional "100" to the entry number of 
the replacement participant and therefore a second replacement would be R206, and so on. 
5.6 
Study Stopping Rules 
After the first group participants (ten or more) dosing, and before the second group dosing, the 
study will stop enrollment when two or more participants have ≥ grade 3 drug-related adverse 
events. The already enrolled participants will be still required to complete the subsequent visits. 
If all 22 participants are dosed, no stopping rules will be set. 
6 
STUDY INTERVENTION(s) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol. 
For the purposes of this protocol, the term study drug may be used synonymously with study 
intervention. 
6.1 
Study Intervention(s) Administered 
Table 6 
Study drug 
Generic Name 
Recombinant Human Thrombopoietin for Injection (rhTPO) 
Type  
Drug 
Dose Formulation 
Lyophilized powder for injection 
Unit Dose Strength(s) 
15000 U/1mL/vial 
Auxiliary materials 
D(-)-Mannitol 40mg, α,α-trehalose dihydrate 20mg, polysorbate 20 
(Tween 20) 0.05mg,  sodium dihydrogen phosphate monohydrate 
0.85mg, and di-sodium hydrogen phosphate dihydrate 0.6mg 
Dosage Level(s) 
300 U/kg 
Route of Administration 
Abdominal subcutaneous injection 
Use 
Experimental 
Dosing Instructions 
A single dose of 300U/kg will be administered through abdominal 
subcutaneous injection. For reconstitution, add 1.1 mL of sterile 
water for injection, sterile powder will quickly dissolve into a clear 
liquid. After reconstitution, this product can be stored at 2-8°C for 72 

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h and at 20-25°C for 24 h (excursions may be permitted between 15-
25°C ), protected from light. It is recommended to use it as soon as 
possible upon reconstitution. Please refer to the Pharmacy Manual for 
details. 
Storage conditions: 
2～8℃, protect from light 
China Marketing 
Authorization Approval 
number: 
State Pharmaceutical Code S20050048 
Sourcing 
Shenyang Sunshine Pharmaceutical Co., Ltd. 
 
6.2 
Preparation, Handling, Storage, and Accountability  
rhTPO For Injection required for this clinical study is managed in accordance with the 
regulations for the management of study drugs in clinical research organizations. The sponsor 
supplies study drugs according to the number of cases of participants in the clinical study unit. 
All investigational drugs are kept in a safe and compliant storage place, and a person is 
responsible for managing the registration and record of investigational drugs. The drug 
administrator records the dosage form, specification, quantity, batch number and expiry date of 
the study drug received from the sponsor. 
Clinical research institutions accepting clinical research drugs must sign a drug receipt form, 
signed by both the sender and receiver, in duplicate, with one copy for each clinical research 
unit and applicant unit. The research organization shall store in the secure access Investigational 
Product (IP) room which is only accessible to site Pharmacy personnel. The 
dispensing/administration of IP will be documented in a timely manner by 2 team members. At 
the end of the study, the remaining drugs and boxes can either be handed over to the sponsor or 
disposed of, and the clinical drugs should not be handed over to any non-clinical study 
participant or third party. 
6.3 
Assignment to Study Intervention 
This is an open-label, single-arm study. Once participants have signed the informed consent 
form (ICF) and enrolled at the site they will be assigned study drug according to the agreed 
participant number (see section 5.5). 
6.4 
Blinding 
Not applicable. 
6.5 
Study Intervention Compliance 
Participants will be administered study drug in a controlled setting directly from the Investigator 
or designee, under medical supervision. All pertinent/required information on the preparation 

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and administration of the dose will be recorded in the source documents and recorded in the 
eCRF. The dose of study intervention and participant identification will be confirmed at the time 
of dosing by a member of the study site staff other than the person administering the study drug. 
For additional information on study intervention compliance and management, refer to the 
Pharmacy Manual. 
6.6 
Prior and Concomitant Therapy 
6.6.1 
Prior Therapy 
The exclusion criteria (Section 5.2) specify that: 
Participants must not have received prescription medication within 14 days prior to dosing and 
7 days prior to dosing for over the counter medication/vitamins/herbal supplements (with the 
exception of contraception, occasional paracetamol < 2g/day, and standard dose of 
multivitamins). 
Participants must not have received a COVID-19 vaccine within 14 days prior to dosing. 
Prior therapy includes medications used by the participant within 28 days prior to the single 
dose of study drug. 
6.6.2 
Concomitant Therapy 
Concomitant procedures are not allowed unless medically indicated. Participants must not 
receive a COVID-19 vaccine for 30 days after dosing. Multivitamins, contraceptives, and 
paracetamol (ie, acetaminophen, at doses of ≤ 2 g/day) are permitted for use during the study at 
the Investigator’s discretion. If medical events (such as, severe hypersensitivity) occur during 
the study period, the participants may receive appropriate medical treatment. Other concomitant 
medication may be considered on a case-by-case basis by the Investigator if required. 
The use of any concomitant therapy (with the exception of medication with no adjunctive 
therapeutic effect, e.g., solvents [sodium chloride], contrast media, etc.) during the study should 
be documented in detail in the original record and electronic clinical report form (eCRF). 
− 
Reason for use. 
− 
Dates of administration including start and end dates. 
− 
Dosage information including dose, frequency and route. 
Since rhTPO is a protein-based macromolecular drug, it may cause anaphylactic reactions 
during and after administration. Adequate preventive and first-aid measures should be taken 
during the study period, e.g., anti-allergic drugs should be prepared at all times. Participants 
should be closely observed for more than 60 minutes after administration, and qualified 
physicians and nurses should be on duty during confinement. First-aid equipment and 

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medication should be available in the study ward. Once a participant is found to have a severe 
allergic reaction, first aid treatment should be given according to the procedures stipulated by 
the site. 
Investigators should ask participants in detail about previous drug or food allergies during 
screening and before administration, and participants with a history of drug or food allergy 
should be enrolled with caution.   
6.7 
Intervention after the End of the Study 
No intervention will be provided to participants at the end of the study. 
7 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation/Withdrawal from the Study 
Participants are free to withdraw from participation in the study at any time upon request. An 
investigator may discontinue or withdraw a participant from the study for the following reasons: 
• 
Pregnancy 
• 
Significant study protocol non-compliance 
• 
If any clinical AE, laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the 
participant 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
Participants may discontinue or withdraw from the study for termination of the study by the 
sponsor or the regulatory authority. 
Note: If a participant tests positive for COVID-19 after administration, an AE should be reported 
and the decision to withdraw from the study should be made based on the AE situation. 
For participants who withdraw early, the investigator must record the reason for early 
withdrawal on the eCRF and carefully complete the final visit record on the eCRF. At the time 
of discontinuing from the study, if possible, an early withdraw visit should be conducted. See 
the SoA (Table 1) for assessments to be collected at the time of discontinuation of study. 
This study endeavours to ensure that sufficient participants receive the study drug. Participants 
who withdraw from the study after enrolment, but prior to receiving study drug may be 
automatically replaced. Participants who withdraw from study after dosing may be replaced at 
the discretion of sponsor and investigator. 

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7.2 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the study site for a required 
study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit and counsel 
the participant on the importance of maintaining the assigned visit schedule, and ascertain 
if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls, texts, 
emails, or local equivalent methods). These contact attempts should be documented in the 
participant’s medical record or study file. 
• 
If the participant continues to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Table 1). 
8.1 
General Procedures 
8.1.1 
Demographic data 
Demographic data will include age or year of birth, gender, and race/ethnicity. 
8.1.2 
Height and weight 
Height and weight will be measured at screening and baseline. BMI will be calculated in the 
formula: BMI = weight (kg)/height2 (m2). 
The data of height and weight will be recorded in the eCRF. 
8.1.3 
Medical History and Prior Therapy 
Medical history related to the inclusion and exclusion criteria, other medical history of clinically 
significant disease starting within 3 months before signing the ICF, surgery history, reproductive 
status (i.e., no childbearing potential or childbearing potential), and allergy history will be 
collected. 
Prior therapy includes medications used by the participant within 28 days prior to the single 
dose of study drug. 

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8.2 
Pharmacokinetics and Immunogenicity 
Blood samples will be collected to characterize the PK profile and anti-drug antibody (ADA) 
of rhTPO. Blood sampling for PK and ADA will be collected at the timepoints specified in Table 
2 and Table 3. 
Samples may be further characterized to determine the titer and the presence of neutralizing 
antibodies (NAb) if positive for ADA. 
Refer to Laboratory Manual for information on the collection, processing, and shipment of 
samples to the Central Laboratory. 
8.3 
Pharmacodynamics 
Hematology test will be performed by the site, in which platelet count (PLT) will be used as an 
indicator of PD. Blood sampling for PD will be collected at the timepoints specified in Table 3. 
8.4 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Table 1).  
8.4.1 
Vital Signs 
Vital signs include systolic and diastolic blood pressure (mmHg), respiration rate (breaths/min), 
heart rate (bpm), and body temperature (°C). Blood pressure (BP) and heart rate will be 
measured after 5 minutes of rest in a supine position in a quiet setting without distractions (e.g., 
television, cell phones). 
Vital signs normal ranges as below:  
SBP: 90 mmHg - 140 mmHg  
DBP: 40 mmHg - 90 mmHg  
Heart rate: 40 - 100 bpm  
Respiration Rate: 10 - 22 breaths/min  
Temperature: 35.5 - 37.5℃ 
8.4.2 
Physical Examinations 
A complete physical examination will be performed and include assessments of the following; 
general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, 
eyes, nose and throat), lymph nodes, thyroid, musculoskeletal (including spine and extremities), 
urogenital, 
dermatological, 
gastrointestinal, 
endocrine, 
hematologic/lymphatic, 
and 

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neurological systems.  
8.4.3 
Electrocardiograms 
ECG parameters including PR Interval, QRS duration, QT Interval, RR Interval, Corrected QT 
Interval (Fridericia) (QTcF), and ECG mean heart rate.  
QTcF = QT/ (RR^0.33). QT is the QT interval, RR is the standardised heart rate value, obtained 
by dividing the heart rate by 60. 
12-lead ECGs will be obtained after the participant has been rested in a supine position for at 
least 10 minutes in the absence of environmental distractions (e.g., television, cell phones). The 
investigator or designated physician will review the 12-lead ECGs. If a participant shows an 
abnormal ECG, the abnormality will be followed to resolution.  
The original ECG traces (per local practice) must be stored in the participant’s medical record 
as source data. 
ECG normal ranges as below:  
Heart rate: 40-100 bpm 
PR Interval: ≥ 120 to ≤ 220 msec  
QRSD: < 120 msec  
QT: < 500 msec  
QTcF ≤ 450 msec both genders 
8.4.4 
Clinical Safety Laboratory Tests 
Blood and urine samples for determination of clinical chemistry, haematology, coagulation and 
urinalysis will be performed by local laboratory. 
Plateletcrit and platelet distribution width are adjunctive pharmacodynamic parameters and they 
will not be reviewed as part of clinical safety laboratory results. 
Participants will abstain from all food at least 8 h prior to any safety laboratory evaluations 
(minimum of 12 h for lipid profile at screening). 
Samples will be taken at the visits indicated in the SoA (Table 1). Allow repeat once for safety 
laboratory assessment to confirm initial result and trending. Blood sample is required as soon 
as possible for hematology in the presence of venous thrombosis. Additional samples may be 
collected if clinically significantly abnormal at the discretion of the investigator. The date, time 

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of collection and results (values, units and reference ranges) will be recorded on the appropriate 
eCRF. 
The following laboratory variables detailed in Table 7 will be measured. 
Table 7 
Laboratory Safety Variables 
Hematology 
Clinical chemistry 
Coagulation 
Urinalysis 
White blood cell count 
with differential (both 
absolute count and 
percentage): 
 
Lymphocyte  
 
Neutrophils 
 
Monocytes 
 
Eosinophil 
 
Basophil 
Red blood cell count 
Hematocrit 
Hemoglobin 
Reticulocyte count 
Platelet count 
mean Platelet volume 
Plateletcrit 
Platelet distribution width 
 
Total bilirubin 
Direct bilirubin  
Alanine 
aminotransferase  
Aspartate 
aminotransferase  
Total protein 
Albumin 
Lactate dehydrogenase  
Creatine kinase  
Troponin  
Gamma-glutamyl 
transpeptidase  
Alkaline phosphatase 
Renal function tests: 
 
Urea 
 
Creatinine 
 
Uric acid 
Lipids: 
 
Total cholesterol  
 
Triglycerides  
Electrolytes: 
• 
Potassium 
• 
Sodium  
• 
Chlorine 
Glucose 
Prothrombin time  
International 
normalized ratio  
Partial 
thromboplastin time 
or activated partial 
thromboplastin time 
Fibrinogen  
D-dimer 
Specific gravity 
PH 
Leukocytes 
Nitrite 
Protein 
Glucose 
Ketone bodies 
Urobilinogen 
Bilirubin 
Blood 
Leukocyte microscopya 
Erythrocyte microscopy a 
a. 
If there are any abnormalities considered clinically significant, the urine sample will be 
sent for microscopic examination. 
8.4.5 
Virology Test 
Blood samples collected at screening will be analysed for the following:  

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− 
HBsAg, HBsAb, HBeAg, HBeAb, HBcAb 
− 
HCV antibody (In the case of positive HCV antibody, the test of HCV RNA will be 
followed) 
− 
HIV antibody 
− 
Syphilis (treponema pallidum particle assay, TPPA) 
Nasopharyngeal or oropharyngeal swab will be collected for Coronavirus Disease 2019 
(COVID-19) RT-PCR test.  
8.4.6 
Serum or Urine Pregnancy Test 
Pregnancy test on urine or blood sample will be performed for female participants of 
childbearing potential. Samples for pregnancy testing will also be performed by local laboratory.  
The serum pregnancy test will be performed at the screening visit, and the urine pregnancy test 
will be performed on Day-1 and afterwards. A serum pregnancy test must be performed if the 
urine pregnancy test is positive or equivocal. 
8.4.7 
Drug Abuse and Alcohol Test 
Breath test and urine drug test will be performed at screening. Urine drug test includes at 
minimum:  
− 
Amphetamines (AMP) 
− 
Methamphetamines (MET) 
− 
Methadone (MTD) 
− 
Barbiturates (BAR) 
− 
Benzodiazepines (BZO) 
− 
Cocaine (COC) 
− 
Opiates (OPI) 
− 
Methyl enedioxy methamphetamine (MDMA) 
− 
Phencyclidine (PCP) 
− 
Tetrahydrocannabinol (THC) 
8.4.8 
Injection site examination 
Injection site examination will be performed at baseline (Day -1) to ensure injection site is 
suitable prior to dosing. 
8.4.9 
Injection site reaction 
Injection site reaction (ISR) is a type of hypersensitivity reaction that may be immediate, 
although it usually appears within 24-48 hours after injection. ISR, by definition, includes the 

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following: erythema, induration, ecchymosis, pain, pruritus, paresthesia, warmth, hemorrhage, 
swelling, etc. at the injection site. ISR will be assessed based on the CTCAE severity scale. 
8.5 
Adverse Events and Serious Adverse Events 
8.5.1 
Definitions 
8.5.1.1 
Definition of adverse event 
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation participant administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to medicinal product. 
 
8.5.1.2 
Definition of Serious Adverse Event  
A serious adverse event is defined as any untoward medical occurrence that at any dose: 
1) Resulting in death. 
2) Life-threatening*. 
3) Results in persistent or significant  disability/incapacity. 
4) Requires hospitalization or prolonged hospitalization**. 
5) Congenital abnormalities/birth defects. 
6) Other important medical events***. 
* The term "life-threatening" in the definition of "serious" refers to an event in which the patient 
was at risk of death at the time of the event; it does not refer to an event which hypothetically 
might have caused death if it was more severe**. Hospitalization means transfer to an inpatient 
unit or emergency ward (usually meaning at least overnight)/intensive care unit for observation 
or treatment. 
The following are not considered hospitalization: 
1) Detention in a doctor's office or outpatient observation room; 
2) Treated only in the emergency room not admitted to the hospital; 

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3) Hospitalization for scheduled surgical or other therapeutic or investigative purposes 
immediately prior to entry into the study, such as elective surgical hospitalization and no 
worsening of underlying disease; 
4) Program-mandated hospitalization (e.g., program-required procedures); 
5) Hospitalization for diagnosis or treatment prior to use of the investigational drug; 
6) Any hospitalization not related to an adverse event, e.g., cosmetic surgery, 
hospitalization for non-medical reasons (e.g., reimbursement, benefits, or convalescence). 
7) Hospitalization or prolonged hospitalization due to social, or convenience or 
administrative reasons (such as annual physical examination, hospitalization for 
reimbursement reasons, etc.). 
Note: If there is a pre-planned hospitalization prior to the start of the study, the investigator will 
need to document this in the medical record and eCRF. 
***Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. Examples of such events include 
intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse. 
8.5.1.3 
Definition of Suspected and Unexpected Serious Adverse Reactions 
Suspected and Unexpected Serious Adverse Reaction (SUSAR) means a serious adverse event 
that meets both of the following conditions: 
Relevant (Related)*: there is a reasonable likelihood of correlation between the adverse event 
and the investigational drug according to the investigator and/or according to the sponsor's 
evaluation; 
Unexpected (Unexpected)**: the nature, severity, consequences, or frequency of the adverse 
event is inconsistent with the safety reference information in the single safety reference 
document for the product specified in the protocol (e.g., investigator's brochure or product 
insert/summary of product characteristics for a marketed product). 
*: For the purposes of this protocol, “related” means “definitely related”, “probably 

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related”, or “possibly related”.  
**: For the purposes of this protocol, the drug safety reference information (RSI) for assessing 
the anticipation of adverse events can be found in: the investigator's brochure for the 
investigational drug. 
8.5.2 
Monitoring and Follow-up 
8.5.2.1 
Monitoring 
Adverse event monitoring time period: from the time of participant signing the ICF until the 
end of the last visit. 
Adverse medical events occurring after the participant has signed the ICF and prior to the first 
dose are recorded in the eCRF as history/concomitant illnesses and are not recorded as AEs 
unless one of the following is met: injury/damage resulting from the operation of any clinical 
laboratory test (AEs related to study operating procedures); AEs resulting from discontinuation 
of medication related to the study protocol; AEs meet SAE severity criteria. 
8.5.2.2 
Follow-up 
The investigator or his/her designee should follow all adverse events occurring during the study, 
with unrelated adverse events followed until the end of the final visit, and related AEs followed 
until the adverse event returns to normal or baseline or stabilizes, or the abnormality is deemed 
by the investigator to be not clinically significant, or is reasonably explained, or the participant 
is lost to follow-up or dies. All AEs in the study must be treated and documented. Any waivers 
must be approved by the sponsor's safety contact. 
For related adverse events, the investigator should follow up until any of the following is 
achieved: 
◼ Events resolved or stabilized; 
◼ The event returns the baseline level, if a baseline value is available; 
◼ The investigators conclude that the abnormalities are not clinically significant; 
◼ Events can be attributed to drugs other than the investigational drug or to factors 
unrelated to the study behavior; 
◼ When more information is unlikely to be available again (patient or healthcare 
professional refuses to provide more information, or there is evidence that the patient is still 
missing visits after best efforts have been made). 

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8.5.3 
Adverse Event Recording 
The investigator should give detailed instructions to the participant and ask the participant to 
respond truthfully to changes in condition after administration of the medication. Physicians 
should avoid inducing questions. While observing the efficacy of the treatment, close attention 
should be paid to observing the adverse events, analyzing the causes, making judgments, and 
conducting follow-up observations and records. 
All adverse events occurring between the signing of the informed consent and the end of the 
last visit must be documented in the appropriate section of the CRF (including the name of the 
adverse event, start/end time, severity, duration, whether it is a serious adverse event, severity 
criteria (if applicable), measures taken on the test medication as a result of the adverse event, 
causal relationship between the adverse event and the investigational drug, outcome, etc.) and 
recorded in detail in the study medical record, whether or not they are study-related, with the 
exception of participants who have withdrawn Informed consent and/or participants who are 
unable to be followed up are excluded. 
The investigator should assess the possible association between the adverse event and the 
investigational drug and coadministration of the drug, as categorized in 8.5.4.2 Assessment of 
Causality. The severity of the adverse event will be graded according to CTCAE version 5.0. 
For each symptom, when there is a change in severity level, the change in severity level needs 
to be documented in detail, and any increase or decrease in severity needs to be documented. 
Any recurrence, worsening, or exacerbation of an AE after remission or return to baseline 
condition will be documented as a new AE. All AEs should be documented in standard medical 
terminology whenever possible. The documented AE should not be an operation (e.g., surgical 
procedure) or a clinical or laboratory test, but rather reflect a known cause leading to the 
operation or clinical/laboratory test. If applicable, the AE should be evaluated and documented 
according to the diagnosis, not the participant's signs and symptoms. However, it may be 
recorded as the participant's signs and symptoms if a definitive diagnosis is not possible. 
All SAEs, whether treatment-related or not, that occur between the time of signing the informed 
consent and the end of the last visit are to be recorded. SAEs that occur at the end of the trial or 
after the end of follow-up until the conclusion of the review need to be reported to the sponsor 
if the investigator considers them to be related to the investigational drug. 
8.5.4 
Assessment of Adverse Event 
8.5.4.1 
Severity Classification 
Adverse drug events will be determined with reference to the Common Terminology Criteria for 
Adverse Events (CTCAE) (version 5.0) criteria for grading adverse events, and parameters not 
covered by CTCAE 5.0 may be interpreted, at the investigator's judgment, on the basis of the 
CTCAE Base Guidelines for Severity Grading or in a similar manner. The CTCAE 5.0 Base 

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Guidelines for Grading are as follows: 
◼ Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; no treatment required. 
◼ Grade 2: Moderate; minimal, local or non-invasive intervention required; limiting age-
appropriate instrumental activities of daily living (e.g., cooking, shopping, using telephone 
and managing money, etc.). 
◼ Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolonged hospitalization indicated; disabling; limiting self-care 
activities of daily life (e.g. bathing, dressing and undressing, feeding self, using toilet, and 
taking medications), but not bedridden. 
◼ Grade 4: Life-threatening; urgent intervention required. 
◼ Grade 5: Death related to AE. 
Symptoms and signs should be described using clear, standardized, and recognized professional 
medical terminology, avoiding colloquial language that is vague and likely to lead to ambiguity. 
8.5.4.2 
Causality Assessment 
− 
Investigators should use their medical knowledge to consider the circumstances 
surrounding the event, and evaluate any potential alternative causes prior to making a 
final causality assessment, i.e., whether there is a reasonable possibility that the study 
drug caused the adverse event. The Investigator should provide the rationale or 
evidence to support the causality assessment as needed. The causality will be assessed 
according to the five-level classification criteria as follows: 
− 
Positively related: The occurrence of AE is determined pharmacologically and is 
reasonably temporally related to the investigational drug. AE disappears or alleviates 
after discontinuation or reduction, and reappears after re administration. AE is not 
related to concomitant medication or non-pharmacological factors (food, participant's 
own illness, environment, etc.); 
− 
Probably related: The occurrence of AE is reasonably temporally related to the 
investigational drug. AE disappears or alleviates after discontinuation or reduction. AE 
is not related to concomitant medication or non-pharmacological factors; 
− 
Possibly related: The occurrence of AE is reasonably temporally related to the 
investigational drug. Remission of the AE after discontinuation or reduction is 
unknown or insignificant, and other factors (e.g., participant's own illness, concomitant 
medication, or non-pharmacological factors) may also contribute to the event; 

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− 
Possibly unrelated: The time relationship between the occurrence of AE and 
investigational drug administration is unclear. AE does not resolve after 
discontinuation or remission is unknown, and concomitant medication or non-
pharmacological factors can explain the AE; 
− 
Definitely unrelated: The occurrence of AE is not reasonably temporally related to the 
investigational drug and/or evidence exists that the AE is definitely related to 
concomitant medication or non-pharmacological factors. 
Because this study is a single administration and does not involve observation of adverse events 
through dose reduction/discontinuation/re-use, the investigator should make a comprehensive 
judgment of relevance based on the metabolic and pharmacodynamic characteristics of the 
investigational drug and the participant's clinical presentation, as well as the possible presence 
of non-pharmacological factors. When there is a change in consistency among test individuals, 
it is more likely to be related to the investigational drug. 
In order to minimize risk to the medication-using population and to comply with regulatory 
requirements, sponsors will address the relevance of the incident in the following manner: 
− 
"Possibly unrelated", "Definitely unrelated", i.e. "unrelated", are categorized as 
unrelated adverse events; 
− 
"Positively Related", "Probably Related", or "Possibly Related" should be considered 
"Related" and categorized as related adverse events. 
8.5.5 
Serious Adverse Event Reporting 
8.5.5.1 
Serious Adverse Event Reporting 
When an investigator is informed of a serious adverse event in a participant during a clinical 
study, he or she should promptly manage and treat the event, whether or not the serious adverse 
event is related to the investigational drug. It should also be reported immediately (within 24 
hours) to the sponsor or the sponsor's designated representative, and the investigator should 
complete, sign and date the full Drug Serious Adverse Event Report Form. 
For reports involving fatal events, the investigator should provide other required information 
such as autopsy reports and final medical reports to the sponsor and ethics committee. 
8.5.5.2 
Serious Adverse Event Notification 
The Clinical Supervisor notifies the Program Manager of all serious adverse events occurring 
in the program species on a quarterly basis, and the Program Manager is responsible for 
notifying all members of this program team. 
8.5.6 
Pregnancy 
If pregnancy occurs in a participant or the female partner of a male participant in the 3 months 
after completion of the study, the investigator should fill out a pregnancy report form and report 

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it to the sponsor or the sponsor's designated representative and the Ethics Committee (if required) 
within 24 hours of being informed. Female participants should withdraw from the trial 
immediately after the occurrence of pregnancy. 
Cases of pregnancy in the trial should be followed up with regard to the outcome of the 
pregnancy as well as the condition of the newborn to determine the outcome of the pregnancy 
(e.g., severe maternal complications, spontaneous or therapeutic abortion, ectopic pregnancy, 
stillbirth, neonatal death, congenital anomalies, or birth defects). In the case of live births, the 
newborn should be followed for up to 12 months following the birth. 
Although the pregnancy itself is not an SAE, complications or serious outcomes resulting from 
the pregnancy that meet the criteria for an SAE must be reported according to the procedures in 
8.5.5. Elective abortion to terminate a pregnancy for no medical reason is not considered an 
AE/SAE. 
8.5.7 
Medication Error 
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength, or 
noncompliance as described in Section 6.1 and 6.2. 
Whether or not the medication error is accompanied by an AE, as determined by the investigator, 
the medication error is recorded on the medication error page of the eCRF and, if applicable, 
any associated AE(s), serious and nonserious, are recorded on an AE page of the eCRF.  
If the associated adverse event fulfils serious criteria, the event should be reported to the 
Sponsor or delegate immediately (i.e., within 24 hours after learning of the event). 
8.5.7.1 
Treatment of Overdose 
For this study, any dose of study intervention greater than that specified in the protocol will be 
considered an overdose. Sponsor does not recommend specific treatment for overdose.  
Overdoses are medication errors that are not considered AEs unless there is an untoward medical 
occurrence resulting from the overdose.  
In the event of an overdose or suspected overdose, the Investigator should： 
1. Contact the Sponsor within 24 hours. 
2. Closely monitor the participant for any AE/SAE. 
3. Obtain a blood sample for PK/PD analysis if requested by the Sponsor (determined on a 
case-by-case basis).  
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 

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9 
STATISTICAL CONSIDERATIONS 
After the study protocol and CRF are completed and finalized, the development of statistical 
analysis plan will be carried out. The statistician will develop the relevant statistical analysis 
plan (SAP) according to the study protocol and the content of CRF, including the content of 
safety statistical analysis and PK, PD, etc. This is an exploratory phase 1 study with no statistical 
hypothesis by using descriptive statistical method, no additional assessments are needed. If 
there're protocol/CRF amendment or some additional analysis to be added during the course of 
study, the SAP will be revised if necessary. And any updates will be tracked with SAP version 
amendment after the initial SAP is finalized. The SAP will be approved by the sponsor before 
database locking. After database locking, the statistical analysis plan will not be modified in 
principle.  
9.1 
Sample Size Determination 
This is an exploratory Phase I clinical study of the pharmacokinetics, pharmacodynamics, safety 
and tolerability of a single dose of Recombinant Human Thrombopoietin for Injection (rhTPO) 
in a single-center, single-arm, open-label, single-dose design in healthy volunteers from a 
Caucasian population. The sample size of this study is not based on statistical hypothesis and 
the study is planned to enrol approximately 22 healthy Caucasian participants. 
9.2 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Table 8 
Populations for Analysis 
Analysis Set 
Description 
Safety analysis set (SS) 
All participants enrolled and receiving the full dose of study drug and have at 
least one post-dose safety assessment. SS will be used for demographics, baseline 
characteristics, and safety analyses. 
PK concentration set 
(PKCS) 
All participants enrolled and receiving the full dose of study drug with at least 
one  evaluable concentration data during the study. PKCS will be used for PK 
concentration analysis. 
PK parameter sets 
(PKPS) 
All participants enrolled and receiving the full dose of study drug with at least 
one  evaluable PK parameter during the study. Participants whose PK parameter 
results affected by major protocol violations will be excluded from the PK 
parameter set. PKPS will be used for PK parameter analysis. 
PD analysis set (PDS) 
All participants enrolled and receiving the full dose of study drug with at least 
one  evaluable PD data during the study, but participants whose PD e results 
affected by major protocol violations will be excluded. The PDS will be used for 
the pharmacodynamic analysis. 
Immunogenicity Analysis 
Set (ADAS) 
Participants with at least one immunogenicity result in the safety analysis set. 
ADAS will be used for immunogenicity analysis. 
 

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9.3 
Statistical Analyses 
This section is a summary of the planned statistical analyses of the most important endpoints 
including primary and secondary endpoints. 
There is no statistical hypothesis associated with the study objectives. As such, no statistical 
tests will be performed. The analyses of safety, efficacy, biomarker and pre-defined subgroups 
will primarily be descriptive. 
9.3.1 
General Considerations 
• 
Analysis software: Phoenix WinNonlin 7.0 software (or above) will be used to calculate 
pharmacokinetic parameters, and all other statistical analyses will be performed using SAS 
9.4 software (or above). 
• 
Baseline definition: the most recent measurement prior to the first dose of investigational 
drug is defined as baseline. If it is missing or cannot be determined then the screening 
period or baseline visit will be taken as baseline. 
• 
Statistical descriptions: quantitative statistical descriptions include: number of cases (N), 
mean (Mean), standard deviation (S.D.), coefficient of variation (CV), median, quartiles 
(Q1/Q3), minimum (Min), maximum (Max), geometric mean, geometric S.D., geometric 
CV. Qualitative statistical descriptions include: frequency and percentages. 
9.3.2 
Participant Distribution, Demographics and Baseline Characteristics 
The distribution of participants will be analyzed using SS. Number of participants screened, and 
the number and ratio of participants who failed screening with reasons will be listed. Calculate 
the number and ratio of participants enrolling, completing the study, and ending the study early 
and their reasons. Summarize protocol deviations by category and severity. Draw a flow chart 
of the distribution of participants. 
Descriptive demographics and other baseline characteristics will be used. 
9.3.3 
Pharmacokinetic Analysis 
Using PKCS, individual and mean concentration-time (c-t) curves and semi-log c-t curves will 
be plotted, and descriptive statistics will be used to list the mean, standard deviation, median, 
quartiles (Q1 and Q3), maximum, minimum, coefficient of variation, geometric mean, 
geometric standard deviation, and geometric coefficient of variation of the PKconcentrations at 
the time points.  
Pharmacokinetic parameters will be calculated for each participant by non-compartment model 
using PKPS with Phoenix WinNonlin 7.0 software (or above), including time to peak drug 
concentration (Tmax ), peak concentration (Cmax ), elimination half-life (t1/2 ), mean residence 
time (MRT), area under the serum concentration-time curve from time zero to the last 
measurable serum concentration time t (AUC0-t), area under the curve extrapolated from zero 

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to time of infinity (AUC0-∞ ), apparent volume of distribution (Vd/F), terminal elimination rate 
constant (Ke), apparent clearance (CL/F), and area ratio under extrapolated concentration-time 
curve (AUC_%Extrap). When calculating pharmacokinetic parameters, samples with 
concentrations below the lower limit of quantification (LLOQ) prior to the Cmax being reached 
should be treated as zero, and as not quantifiable (ND) for LLOQ samples after the Cmax. Also, 
the arithmetic mean, standard deviation, coefficient of variation, median, quartiles (Q1 and Q3), 
maximum, minimum, geometric mean, geometric standard deviation, and geometric coefficient 
of variation will be calculated for pharmacokinetic parameters. For Tmax, only the number of 
observations, median, minimum, and maximum will be listed. When AUC_%Extrap >20%, AUC0-
∞, t1/2, Ke, and AUC_%Extrap will be not analyzed for descriptive statistics but only listed. 
Because of the endogenous substance of TPO in this study, there may be cases of non-below 
quantitation limit (BQL) of concentration in blood samples before administration, if such cases 
occur, baseline correction is required before calculating the pharmacokinetic parameters, and 
the concentration value after administration minus the baseline value is used to calculate the PK 
parameter. If a negative value occurs in the process of calculation, and if the negative value 
occurs before or after quantifiable data, the negative value will be treated as 0. If the negative 
value occurs between two quantifiable data, it is treated as missing. 
Agreement on out-of-window of key PK data points: deviations exceeding the maximum time 
range allowed for non-relevance under the protocol will be considered to be out of window, and 
all PK parameters will be calculated using the actual time of blood sampling, and the actual 
time of blood sampling will be used in plotting the serum concentration-time curve for each 
participant. 
Phoenix WinNonlin 7.0 software (or above) will be used to calculate pharmacokinetic 
parameters, and all other statistical analyses will be done using SAS 9.4 software (or above). 
9.3.4 
Safety Analysis 
The analysis of safety data (AE, TEAE, SAE, clinical laboratory parameters, ECG parameters, 
vital signs, and physical exam) will be descriptive and performed on the safety population. The 
adverse events incidence, overall and per CTCAE grade, will be presented. The attribution to 
the test drugs, time-of-onset, duration of the event, its resolution, and any concomitant 
medications administered will be reported.  
Events will be reported on per-individual basis, i.e. counting individuals rather than events. This 
means that even if a patient suffers the same event repeatedly during the follow-up, the event 
will be counted only once. Repeated events in patients will be summarized according to the 
following rule: if a patient suffers the same event more than once, the event will be assigned the 
worst severity, the closest relationship to the drug and the earliest starting date. In the listings, 
however, all occurrences of the events will be shown.  

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All AEs reported will be classified using frequency and intensity, with the most recent version 
of the MedDRA and listed together with information on onset, duration, seriousness, 
expectedness, relationship, outcome, and countermeasures taken. Serious adverse events will 
be listed separately.  
The absolute and relative frequencies of participants with any AEs will also be listed.  
Furthermore, the absolute and relative frequencies for participants with AEs will be provided 
by System Organ Class and Preferred Term according to the MedDRA. Similarly, degrees of 
intensity, causal relationship with the test drugs, and the countermeasures taken for each AEs 
will be tabulated for each treatment.  The time of onset of AEs after treatment and their duration 
will be evaluated on a categorical basis.   
All clinical laboratory parameters will be analyzed descriptively. Summary statistics for 
baseline, on-treatment, and change from baseline in laboratory, vital signs, and ECG parameters 
will be provided by treatment group in table format. Mean change from baseline over time will 
be plotted with the corresponding standard errors. Values of safety laboratory parameters and 
urinalysis outside the reference range will be flagged as H (above the reference range) or L 
(below the reference range) in the listings. A summary will be prepared by counting both the 
values out of reference range and the number of patients in whom one or more abnormalities 
occurred after treatment. Shift tables may be provided for the changes with respect to reference 
range for the following groups of parameters: hematology, clinical chemistry, and urinalysis.  
For all parameters, these shifts may be tabulated within each treatment and by visit, for the 
comparison before and after treatment.  
Patients with abnormalities for vital signs, ECG, physical exams or clinical laboratory 
parameters will be tabulated and listed in different tables. Abnormality ranges will be defined 
for actual values and for changes from reference. 
9.3.5 
Pharmacodynamics Analysis 
All analyses of pharmacodynamics will be based on the Pharmacodynamics Analysis 
Population (PDS). 
Statistical descriptions of PLT and their differences from baseline at each time point will be 
performed, providing the number of cases, mean, standard deviation, coefficient of variation, 
median, quartiles, minimum, and maximum values. Calculate  the maximum value of the change 
in platelet count relative to baseline (Emax), the time to peak (ETmax), and plot a line graph of the 
mean with standard deviation. 
Line graphs of changes in PLT at each visit for each participant. 
9.3.6 
Immunogenicity Analysis 
ADAS will be used to summarize the immunogenicity data of the participants at different time 

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points. According to the planned timepoints, the number and percentage of ADA positive will 
be summarized and listed. If possible, the titers and NAb for ADA-positive will be further 
analyzed and summarized. 
9.4 
Data Monitor Committee 
No. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
A 1 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with the following: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable Council for Harmonisation (ICH) Good Clinical Practice (GCP)  
− 
Applicable laws and regulations 
• 
Prior to the commencement of the clinical study, the study protocol, informed consent 
form and other information provided to the participants are subject to review and approval 
by the Ethics Committee, and the relevant approvals are provided to the sponsor. Any 
modifications to the protocol and ICF during the study also need to be reported to the IEC 
for approval before implementation. 
A 2 
Informed Consent Process 
The investigator or his/her authorized representative must obtain an informed consent form 
signed by the participants participating in the study and explain to the participants the nature, 
purpose, potential hazards, and benefits of the study, and must let the participants know that 
they may withdraw from the study at any time without restriction. If the participant is unable to 
sign the informed consent form, the participant's legal representative must sign the informed 
consent form. If the participant or their legal representative is unable to read the informed 
consent form, an impartial witness must be present throughout the informed consent process. 
After the participant and his/her legal representative verbally agree to participate in the study, 
the impartial witness must sign the informed consent form and ensure that the participant and 
his/her legal representative are fully informed and understand the contents, and that the 
participant is aware that they may withdraw from the study at any time without restriction. If 
safety results result in a significant change in the risk/benefit assessment, the informed consent 
form is reviewed and changed as necessary, and all participants (including those already 
receiving treatment) must be informed of the updated information and sign the new informed 
consent form before continuing with the study. 

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Both “telehealth discussion and signing” and “in-person discussion and signing” are available. 
Two copies of the informed consent form should be signed and one should be kept with the 
participant, and the other copy of the informed consent form should be kept with the study 
records at the site. The informed consent process should be documented in the participant's 
medical or other original records. 
A 3 
Management of Investigational Drug 
A 3.1 
Packaging and Labeling 
All investigational drugs will be provided to the investigator by Shenyang Sunshine 
Pharmaceutical Co. or its designee. The following information should be stated on the drug 
label: 
− 
Study/Protocol Number 
− 
Specifications 
− 
Storage instructions 
− 
Expiry/Retest Date 
− 
Lot number 
− 
Description of "Clinical study material - Study Use Only", or similar statement 
− 
Name and address of study sponsor/investigational drug manufacturer 
The Investigator or his/her designee shall not provide investigational drugs to any participant 
not enrolled in the study, or to any physician or scientist not appointed to this study. 
A 3.2 
Storage 
The investigational drug shall be kept in a secure locked cabinet or sealed container with strictly 
limited access only to the investigator or his/her designated personnel. Neither the investigator 
nor his/her authorized personnel shall provide the drug to any participant not enrolled in this 
study protocol. 
Investigational drugs should be stored under the conditions specified on the investigational drug 
label. 
A 3.3 
Traceability 
The investigator, or designee, must maintain a detailed inventory record of receipt, distribution, 
use, and retrieval in order to provide assurance to the sponsor that the investigational drug has 
not been distributed to any person other than a participant who meets the deadlines and 
conditions set forth in this study protocol. 
The investigator must securely store the drugs supplied for the conduct of the study. For 

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investigational drugs sent to the study site, the investigator or designee shall confirm the 
quantity sent, the date of acceptance, and that the drug supply will be undamaged and 
uncontaminated in transit, and shall sign and date the appropriate documentation. 
All used and unused/unopened medication containers must be carefully inventoried and kept at 
the site until collected by the sponsor or disposed of. 
A 3.4 
Restitution 
Once the study is nearing completion or termination, all unused and/or partially used study 
medication can be returned to the sponsor or disposed of. 
 
A 4 
Data Management 
A 4.1 
Data Collection 
The Web-based Electronic Data Capture (EDC) Systems will be used to collect, store, and 
manage clinical data. The EDC database builder will establish the electronic case report 
form(eCRF) in EDC according the protocol. Before EDC database go live, the eCRF will be 
approval by Project Managers, Medical Reviewer and Biostatistician etc. The DM will conduct 
the EDC training and introduce the eCRF completion guideline for project managers, clinical 
research associates (CRA), investigators etc. After receiving the training, the relevant personnel 
can log into the EDC system and then enter the data into the eCRF. The EDC system can 
automatically verify the data in the eCRF and generate corresponding prompt messages. After 
the investigators modifying and verifying the entered data, the Principal Investigator or his/her 
authorized Investigators will sign electronically to confirm the data. 
A 4.2 
Data Review 
The CRAs review the data entered into the eCRF by investigators for completeness and 
authenticity, and if necessary, query message to ask investigators to verify and revise until the 
data are accurate, complete and clean; 
The data manager reviews the data entered into the eCRF by investigators for consistency and 
accuracy, and if necessary, query message to ask investigators to verify the changes until the 
data is accurate, complete and clean; 
Medical reviewers to review eCRF data from medical expertise, if necessary, a query to ask 
investigators to verify modifications, until the data are accurate, complete, and clean; 
All data issues should be confirmed before the database lock. The audit trails are required for 
all data changes and related operations. 

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A 4.3 
Database Locking 
If there is a data review meeting or other form of data review communication, the principal 
investigator, medical manager, project manager, data manager, and statistician should confirm 
any protocol deviation events that occurred in the trial and the impact on the statistical analysis 
dataset, and confirm that the database is complete and accurate before co-signing the relevant 
documents to lock the database. In principle, no further changes to the locked database are 
allowed. Problems found after data locking can be updated in the database or explained in the 
report after confirmation, and a written record will be kept. In order to ensure the security of the 
data, unrelated persons are not allowed to approach and modify the data, and the data must be 
backed up. 
A 5 
Quality Control 
A 5.1 
Monitoring 
The sponsor's monitor or representative/designee will visit the site prior to enrolment of the first 
participant at the site and will conduct on-site visits at a planned frequency during the course of 
the study, as well as periodic telephone and written communications. 
After the investigator or clinical research coordinator (CRC) completes data entry, the 
supervisor conducts online for raw data approval (SDV), and the supervisor, medical staff, and 
data manager conduct data verification and send data queries online. After the query is sent, the 
investigator verifies the raw data and resolves the query online. 
A 5.1.1 
Data Requirements for Supervisor Surveillance 
1) Supervisors check for informed consent and screening of participants for inclusion during 
the study; 
2) Verify that all eCRFs are completed correctly and agree with the original information; 
3) All errors or omissions have been corrected or noted, signed and dated by the investigator; 
4) Dose changes, therapeutic alterations, concomitant, and intercurrent illnesses should be 
identified and documented for each participant; 
5) Verify that both withdrawals and lost visits of enrolled participants should be accounted for 
in the eCRF; 
6) Confirmation that all adverse events have been recorded and that serious adverse events 
have been reported and recorded; 
7) Verify that investigational drugs are supplied, stored, dispensed, and withdrawn in 

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accordance with the relevant regulations, and record accordingly; 
8) The eCRF form is completed by the investigator or his/her authorized personnel and the 
eCRF must be completed for each enrolled case. 
A 5.2 
Auditing 
Both sponsors and investigators should establish their own quality assurance systems, fulfil their 
respective responsibilities, and strictly follow the clinical study protocols and adopt the 
appropriate standard operating procedures to ensure the implementation of quality control and 
quality assurance systems for clinical study. 
The sponsor may conduct audits of the above clinical study process, sample testing process, 
data, reports and calculations in different categories as needed, taking into account the progress 
of the study and the results of the verification by the quality controller/supervisor. The 
investigator shall agree to cooperate with the audit in a reasonable manner and at a reasonable 
time. 
A 6 
Study Documentation Management 
A 6.1 
Study Data Acquisition and Modification 
At each follow-up visit of the participant, the investigator participating in the study or his/her 
designee shall document in the study medical record the content of the visit to the participant, 
the examination and observations, etc., which shall include, at a minimum: 
1) Documentation of the process of obtaining informed consent, including various revised 
consent forms. 
2) Dates and days of follow-up visits and visits equivalent to their follow-up in the study 
schedule. 
3) Overall participant status, including all significant medical findings. The severity, 
frequency, and duration of various adverse events and the investigator's assessment of their 
causal relationship with the investigational drug, study manipulation, and other 
concomitant medications must also be documented. 
4) Various changes in concomitant medication or dosage levels. 
5) A general reference to the completed operation. 
6) Signature and date of the clinical staff member who wrote the chart entry and/or 
signature and date of the investigator. 

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In addition, clinically significant information discovered by contacting participants by 
telephone or other means should also be documented in the study medical record as required by 
the methodology described above. 
Any changes to information in the study chart and other original documents should be initiated 
and dated on the day of the change by the investigator who authorized the change. Amendments 
should be made by drawing a single straight line through the incorrect data and clearly 
documenting the correct data. If the reason for the modification is not obvious, a brief 
explanation of the modification should be provided by the Investigator on the original 
documentation. For participants who withdraw early, only the withdrawal follow-up should be 
completed. 
A 6.2 
Original Documents 
Original documentation is defined as all information contained in the original records necessary 
for study reconstruction and evaluation in a clinical study, as well as qualified copies of original 
records of clinical findings, observations, or other items. Original documentation includes 
progress notes, electronic data, screening records, and recorded data from automated 
instruments. 
All original documents related to this study will be kept by the investigator. The investigator is 
obliged to allow study-related surveillance, audits by the sponsor or its appointees, reviews by 
the IEC and inspections by the competent authorities. 
A 6.3 
Document Management at the Study Site 
Investigators are responsible for ensuring that study site documentation is maintained in 
accordance with GCP guidelines. 
A 6.4 
Record-keeping at the Study Site 
The principal investigator is obliged to keep study records and data for safety information 
traceability and audit and visual inspection after the study has ended. The primary 
documentation should be kept until at least 5 years after the completion or discontinuation of 
the study. However, if required by relevant regulations or if requested by the sponsor, the above 
documents should be kept for a longer period of time. Samples, documents and computerized 
records should be kept in a secure area to prevent trespassing, loss or interference. 
The investigator may not dispose of any records related to this study without the following 
permission: 
⚫ Written permission from the sponsor. 
⚫ Provide opportunities for sponsors to collect such records. 

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The investigator shall be responsible for maintaining adequate and accurate electronic or paper-
based source documentation of all observations and data generated during this study. Such 
participant documentation is the basis for visual inspection by the sponsor and relevant 
authorities. If the investigator withdraws from the study (e.g., change of position or retirement), 
study-related records should be transferred to a mutually agreed upon designee. The sponsor 
shall be notified in writing of such transfer. 
A 6.5 
Record-keeping for Sponsors 
The sponsor will maintain all essential sponsor-specific documents in accordance with the 
appropriate regulatory requirements of the regulatory authority. If the sponsor discontinues the 
clinical development of an investigational drug (i.e., due to any or all of the indications, routes 
of administration, or dosage forms), the sponsor will maintain essential sponsor-specific 
documentation until at least 5 years after the formal discontinuation or as required by the 
relevant regulations. 
If the sponsor discontinues clinical development of the investigational drug, the sponsor should 
notify all investigators/institutions and all relevant authorities. 
Important documents that are proprietary to the sponsor should be kept until at least 5 years 
after the completion or discontinuation of the study. However, these documents should be 
retained for a longer period of time if required by relevant legislation or if requested by the 
sponsor. 
The sponsor shall notify the investigator/institution in writing of the record (original and/or 
study base document) retention requirements and shall notify the investigator/institution in 
writing when records related to the study are no longer required to be maintained. 
A 7 
Confidentiality 
All information generated during the study shall be kept in the highest degree of confidentiality 
and shall not be disclosed to anyone not directly related to the study without the written 
permission of the participant. However, direct access may be granted to authorized management, 
sponsor personnel (or their representatives) and the IEC to inspect and copy these records. Only 
participants who have signed an informed consent form may be enrolled in this study. All 
applicable data confidentiality provisions must be fully complied with. All investigational drugs, 
participant body fluids, and/or other collected materials shall be used exclusively in accordance 
with the protocol of this study, unless written consent is obtained from the sponsor. 
All pages of the eCRF and all reports and correspondence pertaining to participants in the study 
shall be distinguished only by the participant's abbreviation of name letters (The four spaces of 
the participant's name abbreviation should be filled in, consisting of the first two letters of the 
first name and the first two letters of the last name), and by the participant's number. The 

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investigator should keep a list of the identification codes of the participants in this study. This 
information shall be kept in the strictest confidence and shall be used only in case of emergency 
if required. 
A 8 
Publication Policy 
Relevant data about this study will be published only with the consent of the research unit and 
the sponsoring organization. 

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11 
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11, pp. 746-754, 1998. 
[3] J. Chen, L. Herceg-Harjacek, J. E. Groopman, and J. Grabarek, "Regulation of platelet 
activation in vitro by the c-Mpl ligand. thrombopoietin," Blood, vol. 86, no. 11, pp. 4054-
4062, 1995. 
[4] Borge OJ, Veiby OP, Martin V et al. Thrombopoietin, but not erythropoietin promotes 
viability and inhibits apotosis of multipotent murine hematopoietic progenitor cells in vitro. 
Blood, 1996, 88(8): 2859-2870. 
[5] Sitnicka E, Lin N, Priestley GV, et al. The effect of thrombopoietin on the proliferation and 
differentiation of murine hematopoietic stem cells. Blood, 1996, 87(12): 4998-5005.