Clinical trial NCT05817708
Conditions: COVID-19
Sponsor: Senhwa Biosciences, Inc.
Start date: 2022-11-28; Completion date: 2023-06-20
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase I single center, open-label, parallel design in 30 subjects to evaluate safety and tolerability of CX-4945 200mg QD, 200 mg BID and 400mg BID doses (10 subjects in each regimen) for continuously 5 days in healthy subjects for dose selection.

Detailed description:
COVID-19 is characterized by SARS-CoV-2 induced up-regulation of host protein kinase CK2 that catalyzes phosphorylation of many proteins, modulating their activities in cellular processes. CX-4945 demonstrated anti-viral efficacy in COVID-19 in vitro studies. In CX4945-AV01-IIT(IND 152726), CX-4945 was a safe treatment at 1000 mg BID regimen supported by the fact of no occurrence of treatment related Grade ≥ 3 AE, death or SUSAR. There were approximately 50 % of patients who experienced gastrointestinal disorders of grade 1-2. In CX4945-AV01-IIT, an out-patient study, there were 50% experienced gastrointestinal disorders. To further evaluate the safety and tolerability of CX-4945, this phase 1 study will use lower doses and subjects will be close-monitored to evaluate the safety.

Arms: arm 1: CX-4945 will be administered at 200mg QD for continuously 5 days. arm 2: CX-4945 will be administered at 200mg BID for continuously 5 days. arm 3: CX-4945 will be administered at 400mg BID for continuously 5 days.
Interventions: intervention 1: CX-4945
Intervention descriptions: intervention 1: Drug: CX-4945

Silmitasertib, orally, once or twice daily for 5 days.

Other Name: Silmitasertib

Protocol documents:
Prot_000.pdf: 
 
A Dose Selection Phase 1 Study Evaluating the Safety and Tolerability of 
Silmitasertib (CX-4945) in Healthy Subjects 
 
Protocol Number: 
CX4945-AV04-phase I  
Protocol version : 
1.0 
Date: 
30-August-2022 
Study Product: 
Silmitasertib (CX-4945) 
Sponsor:  
Senhwa Biosciences, Inc. 
10F, No. 225, Sec. 3, Peihsin Rd.,  
Hsintien Dist., 
New Taipei City 23143, Taiwan 
 
Telephone: +886-2-8911-9856 
 
 
 
 


 
 
  
 
  
 
 
 
 
 




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TABLE OF CONTENTS  
Page 
1. PROTOCOL SUMMARY ......................................................................................................8 
1.1. Synopsis ..........................................................................................................................8 
1.2. Schema ..........................................................................................................................10 
1.3. Schedule of Activities (SOA) ......................................................................................11 
2. INTRODUCTION AND BACKGROUND .........................................................................13 
2.1. Study Rationale............................................................................................................13 
2.2. CX-4945 ........................................................................................................................13 
2.3. Overall Risk and Benefit Assessment ........................................................................15 
3. STUDY OBJECTIVES AND ENDPOINTS ........................................................................17 
4. STUDY DESIGN ....................................................................................................................18 
4.1. Overall Design..............................................................................................................18 
4.2. Justification for dose ...................................................................................................18 
4.3. Study Stopping Criteria ..............................................................................................19 
4.4. End of Study Definition ..............................................................................................19 
5. STUDY POPULATION ........................................................................................................20 
5.1. Subject Eligibility Criteria .........................................................................................20 
5.1.1.Inclusion Criteria ..................................................................................................20 
5.1.2.Exclusion Criteria .................................................................................................20 
5.2. Screen Failures ............................................................................................................21 
5.3. Subject REPLACEMENT ..........................................................................................21 
6. STUDY TREATMENT .........................................................................................................22 
6.1. Study Treatment Administration ..............................................................................22 
6.1.1.Investigational Drug Product Description ............................................................22 
6.1.2.Dosing and Administration of CX-4945 ..............................................................22 
6.1.3.CX-4945 Compliance ...........................................................................................22 
6.1.4.CX-4945 Dose Discontinuation ...........................................................................22 
6.2. INVESTIGATIONAL PRODUCT SUPPLIES, STORAGE AND ACCOUNTABILITY ...............23 


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6.2.1.Investigational Product Supplies ..........................................................................23 
6.2.2.Formulation, Appearance and Packaging .............................................................23 
6.2.3.Product Storage and Stability ...............................................................................24 
6.3. CONCOMITANT MEDICATION .......................................................................................24 
6.4. CX-4945 DRUG INTERACTION .....................................................................................24 
7. STUDY COMPLETION OR DISCONTINUATION ........................................................25 
7.1. Subject Completion .....................................................................................................25 
7.2. Subject Withdrawal from Participation in the Study ..............................................25 
7.3. Subject Discontinuation from Study Treatment ......................................................25 
8. STUDY ASSESSMENTS AND PROCEDURES ................................................................27 
8.1. Study Procedures .........................................................................................................27 
8.1.1.Screening Period: .................................................................................................27 
8.1.2.Treatment Period: .................................................................................................27 
8.1.3.Follow Up Period .................................................................................................27 
8.1.4.Unscheduled Visits ...............................................................................................28 
8.2. Assessments ..................................................................................................................28 
8.2.1.Safety Assessment ................................................................................................28 
8.3. Adverse Events (AEs) and Serious Adverse Events (SAEs) ....................................30 
8.3.1.Definitions of AE .................................................................................................31 
8.3.2.Definition of SAEs ...............................................................................................31 
8.3.3.Classification of AEs ............................................................................................31 
8.3.4.Reporting of AEs ..................................................................................................33 
8.3.5.Reporting of SAEs................................................................................................34 
8.3.6.SAE Follow-Up ....................................................................................................34 
9. STATISTICAL ANALYSIS .................................................................................................36 
9.1. Treatment Cohorts ......................................................................................................36 
9.2. Description of Study Outcomes (Endpoints) ............................................................36 
9.2.1.Safety Measures: ..................................................................................................36 
9.3. Sample Size Determination and Rationale ................................................................36 
9.4. Blinding ........................................................................................................................37 
9.5. Interim Analysis ..........................................................................................................37 


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9.6. General Statistical Considerations.............................................................................37 
9.6.1.Analysis Populations ............................................................................................37 
9.6.2.Missing Data.........................................................................................................37 
9.7. Analysis Methods .........................................................................................................37 
9.7.1.Subject Disposition...............................................................................................38 
9.7.2.Demographic and Baseline Characteristics ..........................................................38 
9.7.3.Concomitant Medications/Therapies ....................................................................38 
9.7.4.Study Outcome Assessment .................................................................................38 
10. DATA MONITORING COMMITTEE (DMC) ..................................................................40 
11. DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ......................................41 
12. QUALITY CONTROL AND QUALITY ASSURANCE ...................................................42 
12.1. Monitoring Requirements ..........................................................................................42 
12.2. Modification of Protocol .............................................................................................42 
12.3. Reporting Protocol Deviations ...................................................................................42 
12.3.1.Major Protocol Deviation or Violation ..............................................................42 
12.3.2.Minor Protocol Deviation or Violation ..............................................................43 
13. ETHICS AND REGULATORY REQUIREMENTS .........................................................44 
13.1. Institutional Review Board/Independent Ethics Committee (IRB/IEC) ...............44 
13.2. Investigator’s Responsibilities ....................................................................................44 
13.3. subject Informed Consent Requirements..................................................................45 
14. DATA HANDLING AND RECORD KEEPING ................................................................46 
14.1. Recording and Collection of Data ..............................................................................46 
14.2. Archiving ......................................................................................................................46 
15. PUBLICATION PLAN .........................................................................................................48 
16. REFERENCES .......................................................................................................................49 
 
 
 
 
 
 


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LIST OF TABLES 
Page 
Table 1: Schedule of Activities ......................................................................................................11 
Table 2. Safety Laboratory Tests ...................................................................................................29 
Table 3. CTCAE v5.0 General Guidelines ....................................................................................31 
 




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Study 
Population: 
This study will enroll male and non-pregnant female ≥ 20 years of age with healthy 
subjects. Totally 30 subjects will be hospitalized and enrolled in this study. 
Phase: 
I 
Description 
of Study 
Intervention: 
CX-4945 will be administered at 200mg QD, 200mg BID or 400mg BID for 
continuously 5 days.  
Study 
Duration: 
5 months (from study initiation until completion of data analyses) 
Subject 
Duration: 
The total duration of the treatment will be 5 days. Subjects will be followed up at 14 
days from the start of the treatment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.2. 
SCHEMA 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
(Baseline) 
 
 
 
Days 2-5 
 
 
 
 
Day 6/EOT 
 
 
 
Follow-up 
Phase 
Day 14 
 
 
 
Total N = 30:   Obtain informed consent. Screen potential subjects by 
inclusion and exclusion criteria; obtain history, complete screening 
200mg QD  
CX-4945, N=10 
Final Assessments 
of adverse event and safety 
evaluations 
Perform baseline assessments. 
- refer to Table 1: Schedule of Activities  
 Starting of CX-4945 Administration 200 mg PO QD, 200mg PO BID or 400mg BID  
Perform visit procedures as specified in Table 1: Schedule of Activities 
CX-4945 Administration 200 mg PO QD, 200mg PO BID or 400mg BID on Day1-Day 5 
Perform Day 6/EOT visit procedures as specified in Table 1: Schedule of Activities 
200mg 
BID 
CX-4945, N=10 
400mg 
BID 
CX-4945, N=10 


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1.3. 
SCHEDULE OF ACTIVITIES (SOA) 
Table 1: Schedule of Activities 
Procedure/Assessments 
Screening 
Visit 
Treatment  
 
Follow-
Up  
Day 
SV 
Day -28~ 0 
Day 1 
(Baseline) 
Day 3 
Day 5 
Day 6 (EOT) 
Day 14 
Window Period 
 
within 28 days 
after SV 
 
 
 
±3 days 
Informed Consent [1] 
X 
 
 
 
 
 
Eligibility Evaluation [2] 
X 
 
 
 
 
 
Subject Demographics  
 
X 
 
 
 
 
 
Medical History [3] 
X 
 
 
 
 
 
Physical Examination 
X 
X 
X 
X 
X 
X 
Weight and Height  
X 
 
 
 
 
 
Vital Signs [4] 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
X 
 
Laboratory Tests:  
X 
X 
X 
X 
X 
X 
Hematology [5] 
X 
X 
X 
X 
X 
X 
Blood Biochemistry [6] 
X 
X 
X 
X 
X 
X 
Coagulation [7] 
X 
X 
X 
X 
X 
X 
Serum/Urine Pregnancy Test [8] 
X 
X 
 
 
 
X 
Urinalysis [9] 
X 
X 
X 
X 
X 
X 
Anti-HIV, Anti-HBV, Anti-HCV 
X 
 
 
 
 
 
Anti-SARS-Cov2 [10] 
 
X 
 
 
 
 
IP Administration  
 
 
CX-4945 200 mg QD daily (Day 1 to 
Day5)  
CX-4945 200 mg BID daily (Day 1 
to Day5) 
CX-4945 400 mg BID daily (Day 1 
to Day5) 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 


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Adverse Events 
 
X 
X 
X 
X 
X 
[1] Informed consent must be obtained prior to subject participation in any protocol-related activities that are not part of routine care. 
[2] Initial evaluation of subject eligibility will be performed by Investigator. Subject number will be assigned on Day1 after confirming the subject eligibility.  
[3] Medical history and current therapies (medications and non-medications). 
[4] Vital signs will include blood pressure, heart rate, respiration rate, SpO2, and temperature. 
[5] Hematology: Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total, differential count,(Absolute Neutrophil 
Count, Absolute Lymphocytes Count, Absolute Monocytes Count, Absolute Eosinophils Count, Absolute Basophils Count) and platelets.  
[6] Blood biochemistry: 
• 
Hepatic function indicators: total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
total protein, albumin, lactate dehydrogenase (LDH) 
• 
Renal function indicators: BUN, Serum creatinine  
• 
Electrolytes: sodium, potassium, chloride, magnesium, phosphorus, total calcium and bicarbonate, 
• 
Other: Creatine phosphokinase (CPK), C-reactive protein (CRP), Creatine kinase-MB(CK-MB mass), Triglyceride, Total Cholesterol, Glucose 
AC, Uric Acid, γ-GT. 
  
[7] Coagulation: Prothrombin time (PT) and International Normalized Ratio (INR) 
[8] ONLY performed on women of childbearing potential. Pregnancy Test will be tested on screening, Day 1 prior dosing and Day 14. 
[9] Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, occult blood, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, and 
microscopic examination of urine sediment. 
[10] In response to the COVID-19 pandemic, the subject will need to follow the currently site’s policies for COVID-19 to get the negative results of anti-SARS-Cov2 test 
before admission.  
 


 
 
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2. 
INTRODUCTION AND BACKGROUND 
2.1. 
STUDY RATIONALE 
The COVID-19 pandemic is an ongoing global pandemic caused by severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China. 
As of 28 July 2022, more than 573 million cases have been confirmed, with more than 6.39 million 
deaths attributed to COVID-19. Symptoms of COVID-19 are highly variable, ranging from none 
to life-threatening illness. The virus spreads mainly through the air from person to person. Common 
symptoms include headache, loss of smell and taste, nasal congestion and rhinorrhea, cough, muscle 
pain, sore throat, fever, diarrhea, and breathing difficulties. Most people develop mild to moderate 
symptoms. 
 
 
 
 
 
 
 
 
Protein kinase, CK2, is a constitutively active serine/threonine kinase which has been studied as a 
pro-survival, anti-apoptotic kinase. Overexpression of CK2 has been reported in multiple cancers 
and shown to be linked to disease progression and poor prognosis. CK2 plays a crucial role in 
multiple non-oncogenic processes required to sustain the cancer phenotype, including the 
Hedgehog (Hh) pathway. Apart from oncology diseases, overexpression of CK2 has also been 
observed in some auto-immune and inflammatory diseases in vivo, and viral infections. 
 
 
 
 
 
Understanding the safety and efficacy of CX-4945 will be the key of targeted COVID-19 
therapies that can be used against the activated CK2 kinase signaling pathway in COVID-19. 
 
2.2. 
CX-4945 


 
 
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CX-4945 is currently under development in several oncology programs in adults and in children 
with recurrent/advanced or metastatic cancer.  CX-4945 is used as an antitumor agent that inhibits 
the Sonic Hedgehog signaling pathway (basal cell carcinoma, medulloblastoma) and/or DNA repair 
in tumor cells damaged by chemotherapy (cholangiocarcinoma) through inhibition of CK2. Three 
phase I clinical trials of CX-4945 in cancer patients have been completed to date (solid tumors, 
multiple myeloma), and there is one ongoing phase I study (basal cell carcinoma) and two ongoing 
phase II studies (cholangiocarcinoma, medulloblastoma). 
  
 
 
 


 
 
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2.3. 
OVERALL RISK AND BENEFIT ASSESSMENT 
In the context of complications potentially associated with SARS-CoV-2 virus infection and the 
limitation of effective preventative measures in COVID-19 epidemics, the established pre-clinical 
toxicological profiles and mechanism of action of CX-4945 supports a favorable benefit/risk 
relationship of the product. This favorable relationship should translate into improved compliance 


 
 
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and offers an alternative program for mild to moderate COVID-19 treatment. It is hoped that the 
safety tolerability and the value of dose selection will be demonstrated in this healthy volunteer 
study, with sufficient safety data generated to enable dose selection for larger and more definitive 
Phase 2 studies. 
 
 




 
 
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4. 
STUDY DESIGN   
4.1. 
OVERALL DESIGN 
This is a phase I single center, open-label, parallel design in 30 subjects to evaluate safety and 
tolerability of CX-4945 200mg QD, 200 mg BID and 400mg BID doses (10 subjects in each 
regimen) for continuously 5 days in healthy subjects for dose selection. Up to approximately 30 
subjects will be enrolled into this study. A screening evaluation will occur within 28 days prior to 
Day 1. A subject screening number will be assigned to each subject in successive order of consent 
signing, beginning with S001. At the end of screening all qualified subjects will be assigned 
sequentially to following three treatment cohorts:  
• Cohort 1:  CX-4945 200mg QD 
• Cohort 2: CX-4945 200mg BID 
• Cohort 3: CX-4945 400mg BID 
A subject number will be assigned to participants when they have confirmed eligible for the study 
on Day1. Each cohort will receive a unique numeric designation, and will precede the subject 
number (e.g. at cohort 1 the first two subjects would be 01-001 and 01-002; at cohort 2 the first two 
subjects would be 02-001 and 02-002). 
The total duration of the treatment will be 5 days. Subjects will be followed up at 14 days from the 
start of the treatment. The total duration for each subject in the study (including the screening) will 
be up to 42 days.   
4.2. 
JUSTIFICATION FOR DOSE 
 
   
 
 
 
 
 
 
 
 
 
 


 
 
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4.3. 
STUDY STOPPING CRITERIA 
During the study, serious adverse events will be reviewed by the sponsor as they are reported from 
the investigational center to identify safety concerns. The study may be terminated by the sponsor 
at any time. 
At any time during the study and after discussion between the sponsor medical officer, medical 
monitor and investigator, the study may be stopped or terminated if the 
following occur: 
1. Previously unknown data that raise concern about the safety of the study participants become 
available 
2. Three or more subject have experienced a clinical laboratory AE of Grade 3 or higher determined 
to be possibly or probably related to CX-4945. 
4.4. 
END OF STUDY DEFINITION 
A subject is considered to have completed the study if he or she has completed the Treatment Phase 
and Follow-up visits (Days 14). 
Discontinuation from CX-4945 does not mean the withdrawal from the study assessments. Subjects 
who discontinued therapy should remain in the study and continue follow-up for key outcomes. 
The only reasons for end of study are withdrawal of consent and loss to follow-up,  
 


 
 
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5. 
STUDY POPULATION 
This study will enroll up to approximately 30 healthy normal volunteers. All qualified subjects will 
be assigned sequentially to three treatment cohorts, CX-4945 200mg QD, 200 mg BID and 400mg 
BID doses and be hospitalized for 6 days treatment.  
5.1. 
SUBJECT ELIGIBILITY CRITERIA 
This study can fulfill its objectives only if appropriate subjects are enrolled. The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol. 
 
5.1.1. Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study: 
1. Healthy  male  and female subjects 20 to 55 years of age, inclusive, at screening 
2. Body mass index (BMI) within the range of 18.0 to 30.0 kg/m2, inclusive, and a minimum weight 
of 50.0 kg at screening  
3. Subjects who are of reproductive potential agreed to remain abstinent or use (or have their 
partner use) an acceptable method of birth control (intrauterine device, hormonal 
contraception, vasectomy or condom) from screening until at least 2 weeks after the last 
study drug administration. 
4. Physically and mentally healthy subjects as confirmed by an interview, medical history, 
clinical examination, and electrocardiogram; 
5. Subject with acceptable hematology, biochemistry and urinalysis during screening period.   
6. Subject is willing and able to comply with study procedures and sign informed consent. 
 
5.1.2. Exclusion Criteria 
Potential subjects meeting any of the following criteria will be excluded from participation in this 
study: 
 
1. Pregnant or nursing women.  


 
 
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NOTE: Women of child-bearing potential and men must agree to use adequate 
contraception (hormonal or barrier method of birth control; or abstinence) prior to study 
entry and from screening until at least 2 weeks after the last study drug administration. 
Should a man father a child, or a woman become pregnant or suspect she is pregnant while 
participating in this study, he or she should inform the treating physician immediately. 
2.  Active or uncontrolled infections such as COVID-19, HIV or with serious illnesses or 
medical conditions which would not permit the subject to receive study treatment. 
3. Subject has received any prescription of drug within 3 days prior to study enrollment.  
4. Subject has drug abuse history.  
5. Any active or recurring clinically significant hepatic disease including HBV and HCV. 
6. Subject has received any investigational agent within 28 days or 5 half-lives, whichever is 
longer, prior to the first dose of investigational product. 
7. Any other medical reason as determined by the investigator. 
5.2. 
SCREEN FAILURES 
All subject who fail to meet eligibility criteria are considered screen failures, and are exited from 
the study. Screening number, demographics and reason for screen failure will be recorded. 
If a subject initially fails to meet inclusion/exclusion criteria and is later reconsidered for 
participation, the subject will be re-consented and assigned a new unique identification number at 
the time of re-screening and may be enrolled if they are found to meet all inclusion and no exclusion 
criteria at the subsequent screening visit. 
5.3. 
SUBJECT REPLACEMENT 
All subjects who are removed from the study for any reason other than for adverse events (e.g., 
voluntary discontinuation at the subjects request, or a severe violation of the study protocol) will 
be replaced. Data from these removed subjects will be included in the overall safety analysis. If 
subject completed the treatment (Day1 to Day5) but not finished the Day 14 follow up visit, the 
subject will not be replaced.  


 
 
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6. 
STUDY TREATMENT 
6.1. 
STUDY TREATMENT ADMINISTRATION 
6.1.1. Investigational Drug Product Description 
For this study, the investigational product is CX-4945 that will be assigned to the three cohorts.  
Refer to the Investigator’s Brochure for more information. 
 
6.1.2. Dosing and Administration of CX-4945 
Subject enrolled to the treatment cohort 1 will receive 200 mg of CX-4945 QD by mouth, beginning 
on Day 1, and continuously through Day 5. The cohort 2 and cohort 3 will receive 200 mg and 
400mg of CX-4945 BID by mouth, beginning on Day 1, and continuously through Day 5. 
Other oral medications should be taken at least one hour before or 2 hours after ingesting the dose 
of CX-4945 capsules.  
Subjects will take 1-2 200-mg CX-4945 capsules, two hours after the morning meal and two hours 
after the evening meal (dinner) with water. Subjects are advised to take 1 capsule at a time with a 
pause in between each. This method may prevent a clumping effect in the stomach, so a subject can 
take as much as 10 minutes to swallow each capsule. 
CX-4945 will be taken on an empty stomach with at least six ounces (180 mL) of water. After CX-
4945 administration, the subject will be NPO (except for water) for 2 hours, after which, the subject 
may eat. 
Subject will take 3 meals a day provided by hospital. If any reason to have an extra food should be 
approved by investigator. Subjects are not allowed to smoke during the 5 days treatment.  
6.1.3. CX-4945 Compliance 
Site staff will dispense CX-4945 to the subjects assigned to the cohort 1, 2 or 3. The site staff will 
make sure that the subject will take the IP properly. Any missed doses or non compliance should 
be documented in the dosing record form. The IP will be counted, documented, and recorded by 
site staff. 
6.1.4. CX-4945 Dose Discontinuation 


 
 
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The most common drug related adverse events reported for CX-4945 are predominantly 
gastrointestinal disorders, including nausea, vomiting and diarrhea. Treatment with CX-4945 can 
be discontinued prematurely due to the following reasons: 
o Subject have experienced a clinical laboratory AE of Grade 2 or higher determined 
to be possibly or probably related to CX-4945 
o Withdrawal from the study treatment or participation 
o Pregnancy  
o Lost to follow-up 
o Reported major protocol deviations, as determined by the Investigator or the 
Sponsor 
o Subject is treated with or takes a prohibited medication. 
o If any clinical adverse event, laboratory abnormality, or other medical condition or 
situation occurs that continued treatment under the protocol would not be in the best 
interest of the subject. 
Discontinuation from CX-4945 does not mean the withdrawal from the study assessments. 
Subjects who discontinued therapy should remain in the study and continue follow-up for key 
outcomes. The only reasons for end of study are withdrawal of consent from study participation 
and loss to follow-up. 
6.2. 
INVESTIGATIONAL PRODUCT SUPPLIES, STORAGE AND ACCOUNTABILITY 
6.2.1. Investigational Product Supplies 
CX-4945 will be supplied by Senhwa Biosciences. Study sites will receive CX-4945 prior to 
enrollment of the first subject.  The clinical site pharmacy /qualified staff member will dispense the 
supplies to the subject enrolled to the cohort 1 to 3 in quantities appropriate according to the study 
visit schedule. Any unused product or waste material should be disposed of in accordance with 
local requirements. 
 
 
 
 
 
 
 
 


 
 
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6.3. 
CONCOMITANT MEDICATION 
Investigators should always manage their subjects according to their medical judgement based on 
the particular clinical circumstances. Any drug contain ingredient of activated charcoal (such as 
Norit) are prohibited for 14 days during the study. 
 
 
  


 
 
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7. 
STUDY COMPLETION OR DISCONTINUATION 
7.1. 
SUBJECT COMPLETION 
A subject is considered to have completed the study if he or she has completed the treatment phase 
and Follow-up visits at Day 14.  
Discontinuation from CX-4945 does not mean the withdrawal from the study assessments. Subjects 
who discontinued therapy should remain in the study and continue follow-up for key outcomes. 
The only reasons for end of study are withdrawal of consent from further participation in the study 
and loss to follow-up.  
7.2. 
SUBJECT WITHDRAWAL FROM PARTICIPATION IN THE STUDY 
At any point during the study all subjects have the right to withdraw consent from further 
participation in the study refusing to complete scheduled study assessments and follow-ups without 
prejudice to future care. If the subject refuses further visits, the subject should continue to be 
followed unless the subject withdraws consent for disclosure of future information or for further 
contact. In this case, no further study-specific evaluations should be performed and no additional 
data should be collected. The sponsor/investigator may retain and continue to use any data collected 
before such withdrawal of consent. 
Another reason for withdrawal from study is loss to follow-up. Before a subject is identified as lost-
to-follow up, the site should make all reasonable efforts to contact the subject. These attempts must 
be documented and should include at a minimum one phone call and one certified letter. 
The reason for withdrawal from the study will be recorded in the subject medical records. 
7.3. 
 SUBJECT DISCONTINUATION FROM STUDY TREATMENT 
Subjects may withdraw from treatment at any time at their own request, or they may be  
withdrawn at any time at the discretion of the investigator/sponsor for safety or behavioral reasons, 
or the inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given investigator site.  
All subjects who discontinued from study treatment but maintain consent, should remain in the 
study through the end of the study period for all important safety assessments. 
Investigators considering subject withdrawal from study treatment should contact the medical 
monitor prior to such discontinuation. Subjects who have study treatment discontinued will 
continue to be followed, per protocol, whenever possible. If visits to the site are not possible, 
subjects can be followed via telehealth or other approaches (telephone calls, e-mails, and texts to 
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Subjects who have study treatment discontinued due to a serious adverse event will be followed 
until study completion, resolution or stabilization of the event (whichever occurs later). 
Reasons for withdrawal of study treatment may include: 
• Subject refused further   
• Pregnancy 
• Unacceptable toxicity 
• Significant study therapy non-compliance  
• If any clinical adverse event (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 
 


 
 
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
The study will have three phases: Screening Phase/Visit, Treatment Phase, and Follow-Up Phase. 
A schedule of assessments and procedures is provided in Section 1.3. 
8.1. 
STUDY PROCEDURES 
8.1.1. Screening Period:  
The subject will sign and date the informed consent form (ICF) prior to any study-related 
procedures. The study center will maintain the study-specific screening and enrollment logs at their 
site.  
For screening procedures see the Schedule of Activities in Section 1.3 and Assessments in Section 
8.2.  
8.1.2. Treatment Period:  
For the treatment period procedures see the Schedule of Activities in Section 1.3 and Assessments 
in Section 8.2. 
Subjects who fulfill all the entry criteria and have written informed consent will be enrolled to the 
study. Enrollment is specifically referred to the visit of treatment on Day 1. All subjects will be 5-
days hospitalized during treatment period. Clinical visit will be scheduled to occur at the intervals 
indicated as Table 1.  After confirming satisfaction of check-in procedure, the subjects will be 
assigned a subject number and will have completed the following evaluations and assessments on 
Day 1 prior to treatment: review of any changes in medication history, physical examination, vital 
signs, clinical status –laboratory sample collection for routine serum biochemical, hematologic, 
coagulation analysis.  
Eligible subjects will be assigned to one of cohort groups to receive the study drug. Considering a 
~15% screen failure rate, approximately 45 subjects will be screened in order to recruit 30 evaluable 
subjects. 
During the treatment phase, subjects assigned to the cohort 1 will receive CX-4945 (200 mg) once 
a day for up to 5 days. For cohort 2, subjects will receive CX-4945 (200 mg) twice a day for up to 
5 days. For cohort 3, subjects will receive CX-4945 (400 mg) twice a day for up to 5 days. 
Details on CX-4945 administration can be found in Section 6. 
8.1.3. Follow Up Period  


 
 
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For follow-up procedures see the Schedule of Activities in Section 1.3 Assessments in Section 8.2. 
8.1.4. Unscheduled Visits 
In the event that the subject will return to clinic at a time other than a regularly scheduled study 
visit, the visit will be regarded as an unscheduled visit. Assessments at unscheduled visits are at 
the discretion of the Investigator. All pertinent findings, including adverse events or changes in 
medications, will be noted in the subject medical records. 
8.2. 
ASSESSMENTS 
Every effort should be made to ensure that the protocol-required tests and procedures are completed 
as described. However, it is anticipated that from time to time there may be circumstances outside 
of the control of the investigator that may make it unfeasible to perform the test. In these cases, the 
investigator will take all steps necessary to ensure the safety and well-being of the subject. When a 
protocol-required test cannot be performed, the investigator will document the reason for this and 
any corrective and preventive actions that he or she has taken to ensure that normal processes are 
adhered to as soon as possible. The study team will be informed of these incidents in a timely 
manner. 
8.2.1. Safety Assessment 
Safety assessments will include collection of adverse events (AEs), serious adverse events (SAEs), 
vital signs and physical examination, electrocardiogram (ECG [12-lead]), laboratory assessments, 
including pregnancy tests and verification of concomitant treatments. 
8.2.1.1. 
Pregnancy Testing 
All pregnancy tests used in this study, either urine or serum, must have a sensitivity of at least 25 
mIU/mL. For female subjects of childbearing potential, a negative pregnancy test is required before 
receiving CX-4945 (1 negative pregnancy test at screening and 1 negative pregnancy test at day1 
prior CX-4945 dosing). Following a negative pregnancy test result at screening, appropriate 
contraception must be commenced. For women of childbearing potential subject should have used 
hormonal or barrier method of birth control; or abstinence as highly effective contraception from 
screening until at least 2 weeks after the last study drug administration.  
Subjects who are found to be pregnant during the screening period will be a screen failure. Subjects 
who are found to be pregnant during the treatment period will be asked to discontinue study 
treatment. 
8.2.1.2. 
Adverse Events (AEs) 


 
 
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Assessment of AEs will include the type, incidence, severity (graded by the CTCAE version 5.0) 
timing, seriousness, and relatedness. For AE assessment details, see Section 8.3.3. Investigator will 
follow-up for any AEs/SAEs at Day 14. 
8.2.1.3. 
Vital Signs and Physical Examination 
Subjects will have a full physical examination to include an examination of all major body systems, 
height (at screening only), weight (at screening only), blood pressure, respiration rate, SpO2, 
temperature and heart rate, which may be performed by a physician, registered nurse or other 
qualified health care provider, as acceptable according to local regulation. The physical 
examination, assessing the subject’s overall health and physical condition, will be performed 
according to the site’s SOPs. Changes from baseline abnormalities should be recorded at each 
subsequent physical examination. New or worsened abnormalities should be recorded but only 
clinically significant abnormalities will be recorded as an AE. 
Pulse oximetry should be collected prior to collection of the blood pressure, pulse rate, and 
temperature. Oxygen levels should be evaluated on the finger in accordance with the site’s standard 
procedures. All abnormalities will be evaluated by the study physician.  
Blood pressure, heart rate, respiration rate, and temperature should be recorded after approximately 
5 minutes rest.  
 
8.2.1.4. 
Laboratory Safety Assessment 
Hematology and blood chemistry will be drawn at the time points described in the Schedule of 
Activities (see Section 1.3 ) and analyzed at local laboratories. Unscheduled clinical labs may be 
obtained at any time during the study to assess any perceived safety concerns. Samples for 
hematology, blood chemistry, coagulation, pregnancy and urinalysis will be analyzed by the site’s 
local laboratory.  
Table 2. Safety Laboratory Tests 
Hematology 
Biochemistry 
Coagulation 
Urinalysis 
Pregnancy Test 
Hemoglobin 
ALT 
PT  
color, appearance, 
specific gravity, 
pH, protein, 
glucose, occult 
blood, ketones, 
leukocyte esterase, 
nitrite, bilirubin, 
urobilinogen 
For female 
subjects of 
childbearing 
potential, serum 
or urine 
Hematocrit 
AST 
INR 
RBC 
ALP 
Platelets 
LDH 
WBC 
Total Protein 
Absolute Neutrophils 
Sodium 
  


 
 
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Hematology 
Biochemistry 
Coagulation 
Urinalysis 
Pregnancy Test 
Absolute Lymphocytes 
Potassium 
microscopic 
examination of 
urine sediment 
  
Absolute Monocytes 
BUN 
  
Absolute Eosinophils 
Chloride 
  
Absolute Basophils 
Total Calcium 
  
 
Magnesium 
 
Serology 
 
 
Phosphorus 
 
Anti-HIV 
 
  
Bicarbonate 
Anti-HCV 
  
  
Total bilirubin 
Anti-HBV 
  
  
Creatinine (serum) 
  
  
Albumin 
Others 
  
  
C-reactive protein 
(CRP) 
Anti-SARS-Cov2 
  
  
Creatine 
Phosphokinase (CPK) 
  
  
Creatine kinase-
MB(CK-MB mass) 
  
 
Triglyceride 
 
 
 
 
Total Cholesterol 
 
 
 
 
Glucose AC 
 
 
 
 
Uric Acid 
 
 
 
 
γ-GT 
 
 
 
8.2.1.5. 
Electrocardiogram (ECG) 
An ECG will be done at Screening, Day 1, Day 3, Day 5, and at Day 6. It is preferable that the 
machine used has a capacity to calculate the standard intervals automatically, including QT and 
QTc interval. At each time point (see the Schedule of Activities), if the significant abnormalities 
(>Grade 2) in ECG intervals are revealed, then the ECGs should be re-evaluated by a qualified 
person at the site for confirmation as soon as the finding is made, including verification that the 
machine reading is accurate.  
8.3. 
ADVERSE EVENTS (AES) AND SERIOUS ADVERSE EVENTS (SAES) 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol. During the study when there is a safety 




 
 
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Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age- appropriate instrumental activities of daily living (ADL)*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self care ADL†. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, 
etc. 
†Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
-Common Terminology Criteria for Adverse Events (CTCAE), v5.0: November 27, 2017 
8.3.3.2. 
Causality Assessment 
AEs will be assigned a relationship (causality) to the study treatment. The Investigator will be 
responsible for determining the relationship between an AE and the study treatment. The type of 
event, organ system affected, and timing of onset of the event will be factors in assessing the 
likelihood that an AE is related to the study treatment. Relationship of AEs to study treatment will 
be classified as follows: 
1. Definitely related: This category applies to those AEs that the Investigator feels are 
incontrovertibly related to the study treatment. An AE may be assigned an attribution of 
definitely related if or when it meets all of the following criteria: (1) it follows a reasonable 
temporal sequence from administration of the study treatment; (2) it could not be reasonably 
explained by the known characteristics of the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; (3) it follows a known 
response pattern to treatment with the study treatment. 
2. Probably related: This category applies to those AEs which, after careful medical 
consideration at the time they are evaluated, are felt with a high degree of certainty to be 
related to the study treatment. An AE may be considered probable if or when (must have 
three): (1) it follows a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) Disappears 
or is decreased upon discontinuation of the study treatment. (4) It follows a known response 
pattern to treatment with the study treatment.  
3. Possibly related: This category applies to those AEs which, after careful medical 
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with certainty to the study treatment. An AE may be considered possible if or when (must 
have two): (1) it follows a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) Disappears 
or is decreased upon discontinuation of the study treatment. (4) It follows a known response 
pattern to treatment with the study treatment.  
4. Unlikely related: In general, this category can be considered applicable to those AEs which, 
after careful medical consideration at the time they are evaluated, are judged likely to be 
unrelated to the study treatment. An AE may be considered unlikely if or when (must have 
two): (1) it does not follow a reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by subject’s clinical state, 
environmental or toxic factors, or other therapies administered to the subject. (3) Disappears 
or is decreased upon discontinuation of the study treatment. (4) It does not follow a known 
response pattern to treatment with the study treatment.  
5. Unrelated: This category applies to those AEs which, after careful consideration at the time 
they are evaluated, are clearly and incontrovertibly due to extraneous causes (disease, 
environment, etc.) and determined with certainty to have no relationship to the study 
treatment.  
8.3.3.3. Expectedness 
The Medical Monitor will be responsible for determining whether an AE is expected or unexpected.  
An AE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the information described in the Investigator’s Brochure.  
Refer to the Investigator’s Brochure for the expected/anticipated events. 
8.3.4. Reporting of AEs 
Report initiation for all AEs and SAEs will begin at the time of the first treatment visit and continue 
until the end of final study visit.  All events will be followed to resolution or until the subject 
completes the study. A final assessment of outcome will be made at that time.  
All AEs must be recorded in the subject’s study records. AEs will be reported using customary 
medical terminology along with the following information: the onset and end dates,  whether the 
event is considered to be a SAE (see Section 8.3.2), the impact the event had on study treatment 
(see Section 8.3.4.1), the Common Terminology Criteria for Adverse Events (CTCAE) grade 
(intensity) of the event (see Section 8.3.3.1), the causality of the event (see Section 8.3.3.2, whether 
treatment was given as a result of the event (see Section 8.3.4.2), and the outcome of the event. (see 
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8.3.4.1. 
Impact on Study Treatment 
The impact the event had on the study treatment will be assessed as either: dose increased, dose not 
changed, dose rate reduced, dose reduced, drug interrupted, drug withdrawn, not applicable, or 
unknown. The “not applicable” assessment will be used only when the subject is no longer in the 
Treatment Phase of the protocol. 
8.3.4.2. 
Treatment Given as a Result of the Event 
The event impact in terms of treatment provided will be as either: none, medication administered, 
non-drug therapy administered, surgery performed, hospitalization, or other (with a specification). 
8.3.4.3. 
Outcome Assessment 
The outcome of the event will be assessed as either: fatal, not recovered/not resolved, 
recovered/resolved, recovered/resolved with sequelae, recovering/resolving, or unknown. Only one 
AE per subject is allowed to have an outcome assessment as “death.” If there are multiple causes 
of death for a given subject, only the primary cause of death will have an outcome of death.  
8.3.5. Reporting of SAEs  
The Investigator is required to report all SAEs that occur during the time period specified in Section 
8.3.4. Once the Investigator becomes aware of an SAE, he/she must report the SAE to Sponsor’s 
Contract Research Organization (CRO) Safety Department within 24 hours. 
Safety Department 
 
 
 
 
The designee in Safety Department may request additional supporting documentation as it becomes 
available, such as lab reports, electrocardiogram [ECG] reports, discharge summary, hospital notes, 
etc., if applicable. Additional follow-up information as it becomes available must be reported to the 
designee in Safety Department. 
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified.  
8.3.6. SAE Follow-Up 
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed 
until sufficient information is obtained to indicate a return to normal status or until the event 


 
 
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stabilizes at a level acceptable to the investigator (i.e., recovery, return to baseline status, no further 
improvement expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subjects completed the study or withdrew, the site should submit a follow-up report with updated 
information. 


 
 
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9. 
STATISTICAL ANALYSIS  
This section presents general information about statistical considerations and concepts and a brief 
discussion on analysis methodology, as well as some data conventions. Detailed descriptions of the 
statistical analysis methods and data conventions that will be used in this study will be in a separate 
document [i.e., the Statistical Analysis Plan (SAP)]. 
9.1. 
TREATMENT COHORTS 
There will be three cohorts in the study:  
• Cohort 1:  CX-4945 200mg QD 
• Cohort 2: CX-4945 200mg BID 
• Cohort 3: CX-4945 400mg BID 
The total duration of the treatment will be 5 days. Subjects will be followed up at 14 days from 
the start of the treatment.  
9.2. 
DESCRIPTION OF STUDY OUTCOMES (ENDPOINTS) 
For description of study outcomes see the Objectives and Endpoints in Section 1.1 and Section 3. 
 
9.2.1. Safety Measures: 
• Incidence and severity of AEs 
• Incidence of SAEs 
• Incidence of AEs and SAEs leading to discontinuation of study medication.  
• Changes in blood chemistry (including electrolyte abnormalities), hematology and 
coagulation parameter results 
• Changes in vital signs including temperature, heart rate, respiratory rate, SpO2, systolic and 
diastolic blood pressure, urinalysis 
• Changes in physical examination results 
• Changes in ECG results 
9.3. 
SAMPLE SIZE DETERMINATION AND RATIONALE 
A total of 30 subjects will be assigned sequentially into 3 cohorts in this study. The sample size is 
based on clinical judgment. No statistical power calculation is used to establish the sample size for 
this proof-of-concept study. 
 


 
 
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9.4. 
BLINDING 
This is an open label study. 
9.5. 
INTERIM ANALYSIS 
No Interim Analysis (IA) is planned for this study. 
9.6. 
GENERAL STATISTICAL CONSIDERATIONS 
All collected study data will be presented in subject data listings. Statistical analyses will be 
performed using SAS® for Windows, version 9.4 or later. Descriptive statistics (n, mean, standard 
deviation, median, minimum and maximum) will be presented by treatment group for continuous 
variables. Frequencies and percentages will be presented by treatment group for categorical 
variables. 
9.6.1. Analysis Populations 
9.6.1.1. 
Intent-to-Treat (ITT)Population 
The ITT population is defined as all assigned subjects who received at least one dose of study drug. 
This population will be used as the primary analysis population for analysis of the primary and 
secondary endpoints. 
9.6.1.2. 
Per Protocol (PP) Population 
The PP population is defined as the set of subjects who meet the ITT population requirements and 
are not associated with any major protocol violations. This population will be identified before the 
database lock.  This population will be used as the supportive analysis population for analysis of 
the primary and secondary endpoints. 
9.6.1.3. 
Safety Population 
The Safety population is defined as any subject receiving at least one dose of CX-4945. This 
population will be used for the analysis of safety parameters. 
9.6.2. Missing Data 
The method for handling missing data will be included in the statistical analysis plan. Every effort 
will be made to obtain required data at each scheduled evaluation from all subjects who have been 
assigned in the study to minimize missing data. However, in the event when there are missing data 
the following imputation methods will be used. 
9.7. 
ANALYSIS METHODS 


 
 
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An SAP will be developed and approved before the database is locked. The SAP will present the 
detailed statistical methodology to be used in analyzing the data from this trial. 
9.7.1. Subject Disposition 
The disposition of all subjects who signed an ICF will be provided. The number of subjects screened, 
screen failed, received at least one treatment, completed, and discontinued during the study, as well 
as the reasons for all discontinuations will be summarized by treatment group. Disposition and 
reason for study discontinuation will also be provided as a by-subject listing. 
9.7.2. Demographic and Baseline Characteristics 
Demographics and baseline characteristics including medical history, prior and concomitant 
medications/therapies will be summarized by treatment group using appropriate descriptive 
statistics. 
9.7.3. Concomitant Medications/Therapies 
Concomitant medications/therapies will be summarized separately for the Safety population. All 
prior and concomitant medications recorded in the case report form will be coded to matching 
Anatomic Therapeutic Classification codes using the most recent version of the WHO Drug 
Dictionary. Descriptive summaries by treatment group will be prepared using the coded term. All 
concomitant medications/therapies recorded in the case report form will be listed. 
 
9.7.4. Study Outcome Assessment 
For continuous variables data will be summarized by treatment using n, mean, SD, minimum and 
maximum values. For categorical variables data will be summarized by treatment using frequency 
and percentage. No inferential statistics are planned. The Safety population will be used for the 
analysis of safety outcomes.  
 
9.7.4.1. 
Supportive Analysis  
To assess the consistency of the primary analysis results, supportive analysis will be conducted 
using the ITT and PP populations. Statistical methodology for the supportive analyses will be the 
same as that of the primary analysis, with the exception of the analysis population used.  
9.7.4.2. 
Safety Summaries  
Adverse Events 


 
 
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AEs will be coded using the most recent version of Medical Dictionary for Regulatory Activities 
(MedDRA). Treatment Emergent AE’s (TEAE) are defined as events with an onset on or after the 
first treatment. TEAEs will be summarized by treatment group, system organ class, and preferred 
term. The following TEAE summaries will be provided: 
• Overall (i.e., regardless of severity or relationship to treatment); 
• By intensity (mild, moderate, severe, life threatening or death); 
• By causality (definitely, probably, possibly, remotely or unrelated); 
• By impact on study treatment (dose increased, dose not changed, dose rate reduced, dose 
reduced, drug interrupted, drug withdrawn, not applicable, or unknown). 
In addition, separate summaries of SAEs, and AEs resulting in discontinuation of study treatment 
will be presented. 
Clinical Laboratory Data 
All laboratory values will be listed. Laboratory measurements will also be summarized and 
presented by treatment group and time point. 
ECG 
All ECG values will be listed. ECG measurements will also be summarized and presented by 
treatment group and time point. 
Vital Signs 
All vital sign findings will be listed and/or summarized. 
Physical Examination 
All physical examination findings will be listed and/or summarized. 
 


 
 
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10. 
DATA MONITORING COMMITTEE (DMC) 
Throughout the trial, all safety and tolerability data will be reviewed and monitored by an 
independent DMC. The composition and functions of the DMC will be governed by a charter, 
which will be described elsewhere. 
At a minimum, safety data include all observations generated as part of study procedures and SoC 
that have been captured in the CRF. At the discretion of the DMC, this may be extended to include 
all relevant source records and, potentially, portions of the medical record of clinical care that have 
not been captured in source records. 
The DMC will consist of at least 3 key opinion leaders, of which 1 will serve as the Chairperson. 
Due to the small sample size, a Statistician will not form part of the DMC. Data obtained from the 
all subject will be reviewed by the DMC.  
 


 
 
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11. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION 
Subject will be identified on study records by a unique Subject identification number and on source 
documents by name and date of birth. No personal identifier will be used in any publication or 
communication used to subject this research study. The subject identification number will be used 
if it becomes necessary to identify data specific to a single subject.  
The local IRB, FDA, TFDA the monitors, auditors and personnel authorized by the 
Investigator/Sponsor are eligible to review the medical and research records related to this study as 
part of their responsibility to protect human subjects in clinical research. They will be given direct 
access to source data and documentation (e.g., medical charts/records, printouts etc.) for source 
data verification, provided that subject confidentiality is maintained in accordance with local 
requirements. Access to electronic medical records may be governed by institution policy. The 
Investigator will be required to ensure access while remaining compliant with institutional 
requirements. 


 
 
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12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
12.1. MONITORING REQUIREMENTS 
The Investigator/Sponsor should be aware that the study site and subject records may be inspected 
by the FDA, TFDA or other regional regulatory authority. 
12.2. MODIFICATION OF PROTOCOL 
The Investigator/Sponsor will not modify or alter this protocol without first obtaining the 
concurrence of the Sponsor. Approval by the Investigator/Sponsor’s IRB must also be obtained 
prior to implementation of the change, with two exceptions: 
1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 
An amendment may also require modification of the informed consent form.  
12.3. REPORTING PROTOCOL DEVIATIONS 
The Investigator/Sponsor is obligated to follow the protocol without departure from the 
requirements written in the protocol. The Investigator/Sponsor also has the right to discontinue the 
subject for protocol violations. The IRB may also have to be contacted if safety to the subject or if 
the scientific soundness of the study is involved.  
12.3.1. Major Protocol Deviation or Violation 
A major protocol deviation or violation is a deviation from the IRB approved protocol that may 
affect the subject 's rights, safety, or well-being and/or the completeness, accuracy and reliability 
of the study data. Examples of this include: 
• Failure to obtain informed consent prior to initiation of study-related procedures  
• A research subject does not meet the protocol's eligibility criteria but was enrolled 
• A research subject received the wrong treatment or incorrect dose. 
• A research subject met withdrawal criteria during the study but was not withdrawn. 
• A research subject received a prohibited concomitant medication. 
• Failure to treat research subject per protocol procedures that specifically relate to primary 
outcome measures. 


 
 
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• Changing the protocol without prior IRB approval. 
• Multiple minor violations of the same nature after multiple warnings. 
12.3.2.  Minor Protocol Deviation or Violation 
A minor protocol deviation is any change, divergence, or departure from the study design or 
procedures of a research protocol that has not been approved by the IRB and which does NOT have 
a major impact on the subject 's rights, safety or well-being, or the completeness, accuracy and 
reliability of the study data.  Examples of this include: 
• Follow-up visits that occurred outside the protocol required time frame because of the subject’s 
schedule. 
• Blood samples obtained at times close to but not precisely at the time points specified in the 
protocol. 


 
 
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13. 
ETHICS AND REGULATORY REQUIREMENTS 
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, GCP, 21 CFR, ICH E6, HIPAA 
regulations in 45 CFR Part 164 (US only), and the Belmont Principles of respect for persons, 
beneficence, and justice. No protocol changes will be implemented without the prior review and 
approval of the IRB, except when the modification does not involve the subject’s participation in 
the trial or where it may be necessary to eliminate an immediate hazard to a research subject. In the 
latter case, the change will be reported to the IRB as soon as possible, according to IRB regulations.  
Additionally, the study product used in this study is manufactured, handled and stored in accordance 
with applicable GMP. The study product provided for this study will be used only in accordance 
with this protocol. 
13.1. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) 
The Investigator/Sponsor will provide the Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) with all appropriate materials as required by their IRB/IEC, including but 
not limited to the clinical study protocol, informed consent form, and any advertising materials. 
The study will not be initiated until the IRB/IEC provides written approval of the aforementioned 
document. The Investigator will not participate in the decision. If the Investigator is an IRB or IEC 
member, documentation must be provided indicating recusal from the approval process. 
Appropriate reports on the progress of this study by the Investigator will be made to the IRB/IEC 
as required by local and applicable government regulations. The Investigator is required to maintain 
an accurate and complete record of all written correspondence to and received from the IRB/IEC. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate 
immediate hazards to the subjects or when the modification does not involve the subject’s 
participation in the trial.  
13.2. INVESTIGATOR’S RESPONSIBILITIES 
The Investigators are responsible for performing the study in full accordance with the protocol and 
the current revision of the Declaration of Helsinki, the Good Clinical Practice: Consolidated 
Guideline, approved by the ICH, and any applicable national and local laws and regulations. 
Information regarding to the study center participating in this study that cannot comply with these 
standards will be documented. 


 
 
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13.3. 
SUBJECT INFORMED CONSENT REQUIREMENTS 
All subjects participating in this study will be given to by the Investigator and/or designee, written 
and oral information about the study in a language understandable by the subject. Written informed 
consent will be obtained from each subject prior any procedures or assessments that would not 
otherwise be required for the care of the subject are done and after the aims, methods, anticipated 
benefits, potential hazards, and insurance arrangements in force are explained and the subject has 
been given sufficient time to ask questions and consider participation in the study. It will also be 
explained to the subjects that they are free to refuse entry into the study and free to withdraw from 
the study at any time without prejudice to future treatment. It is permissible for a third person (e.g., 
a family member) to be present during the explanation of the study. 
The written Informed Consent Form (ICF) will be in compliance with CFR 21 Part 50.27 and GCP 
guidelines. A copy of the ICF to be used will be submitted by the Investigator/Sponsor to the 
IRB/IEC for review and approval prior to the start of the study. The original signed ICF is retained 
in the subject 's study records, and a copy is provided to the subject. A second copy may be filed in 
the subject’s medical record, if allowed by institutional policy.  


 
 
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14. 
DATA HANDLING AND RECORD KEEPING 
14.1. RECORDING AND COLLECTION OF DATA 
The primary source document for this study will be the subject 's medical record. If separate 
research records are maintained by the Investigator(s), the medical record and the research records 
will be considered the source documents for the purposes of auditing the study.  
The Investigator will maintain a confidential list of study subjects that will include each subject’s 
study number, name, date of birth, and unique hospital identification number if applicable. A 
notation will be made in the subject’s case history/medical chart that he/she is participating in a 
clinical study and has provided a signed and dated ICF as well as a release for protected health 
information as required by local policies. The Investigator must also maintain a separate screening 
log of all the subjects screened for participation in the study; it should include gender, age, 
eligibility status, reason for ineligibility, if applicable; and study allocated subject number, if 
applicable.  
14.2. ARCHIVING 
All study documentation at the Investigator site will be archived in accordance with ICH GCP E6 
and the Investigator/Sponsor’s quality standards and SOPs. 
The Investigator will maintain all research records, reports, and case history reports for a period of 
two (2) years after regulatory approval of the investigational product. If no application is filed or if 
the application is not approved, records must be maintained for two (2) years after all investigations 
have been completed, terminated or discontinued and the FDA has been notified.  
These documents should be retained for a longer period however, if required by the applicable 
regulatory requirements (as per GCP 5.5.11). 
Study records are subject to inspection by applicable health and regulatory agencies at any time.  
Records to be retained by the Investigator include, but are not restricted to: 
• Source data and the primary records upon which they are based (e.g., subject’s progress 
notes, AE data, test results, and any other diagnostic procedures required to evaluate the 
progress of the study) 
• Signed protocols and protocol amendments 
• Laboratory results, ranges, and certifications 


 
 
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• IP and accountability records 
• Study personnel signature log 
• Monitoring logs 
• Investigator and sub-investigator CVs 
• Signed informed consent and protected health information consent forms 
• Subject screening  
• SAE reports 
• IRB approval and re-approval letters 
• Completed quality of life questionnaire 
• Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Investigator so that the conduct of the 
study can be fully documented and monitored. 
Study records are subject to inspection by applicable health and regulatory agencies at any time.  


 
 
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15. 
PUBLICATION PLAN 
All information supplied by Senwha in connection with this study and not previously published, 
is considered confidential information. This information includes, but is not limited to, the 
Investigator’s Brochure, clinical protocol, case report forms and other scientific data. Any data 
collected during the study are also considered confidential. This confidential information shall 
remain the sole property of Senwha, shall not be disclosed to others without the written consent 
of Senwha, and shall not be used except in the performance of this study. 


 
 
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16. 
REFERENCES 
1. Bouhaddou M, Memon D, Meyer B, et al. The Global Phosphorylation Landscape of SARS- 
CoV-2 Infection. Cell. Published online 2020. doi:10.1016/j.cell.2020.06.034 
2. 12T-1090522-1Q_Testing of the anti-SARS-CoV-2 activity of compounds provided by 
Senhwa Biosciences. 
3. Piirsoo A, Piirsoo M, Kala M, Sankovski E, Lototskaja E, Levin V, et al. (2019) Activity of 
CK2α protein kinase is required for efficient replication of some HPV types. PLoS Pathog 
15(5): e1007788. https://doi.org/10.1371/journal.ppat.1007788 
4. Rosenberger, A.F.N., Morrema, T.H.J., Gerritsen, W.H. et al. Increased occurrence of 
protein kinase CK2 in astrocytes in Alzheimer’s disease pathology. J Neuroinflammation 
13, 4 (2016). https://doi.org/10.1186/s12974-015-0470-x 
5. Eric Ka-Wai Hui, Debi P. Nayak (2002). Role of G protein and protein kinase signalling in 
influenza virus budding in MDCK cells.  JOURNAL OF GENERAL VIROLOGY, Volume 
83, Issue 12 https://doi.org/10.1099/0022-1317-83-12-3055 
6. Koffa MD, Kean J, Zachos G, Rice SA, Clements JB. CK2 protein kinase is stimulated and 
redistributed by functional herpes simplex virus ICP27 protein. J Virol. 2003;77(7):4315‐
4325. doi:10.1128/jvi.77.7.4315-4325. 
 

SAP_001.pdf: 
QPS-Qualitix Clinical Research 
CONFIDENTIAL 
Statistical Analysis Plan
Protocol No.: CX4945-AV04-phase I 
SAP Version: 1.0 
SOP-BDM-016-RD-01, Version 06 (15-Dec-2021) 
Page 1 of 16     
A Dose Selection Phase 1 Study Evaluating the Safety and Tolerability 
of Silmitasertib (CX-4945) in Healthy Subjects  
Protocol No.: CX4945-AV04-phase I 
STATISTICAL ANALYSIS PLAN  
Version: 1.0 
Date: 05.Jan.2023 
Biostatistician: Chen Tung        
Confidentiality Statement 
This document is the property of QPS-Qualitix Clinical Research Co., Ltd., and may not-in full or part-be passed on, 
reproduced, distributed to any person, or submitted to any regulatory authorities without prior written permission from 
QPS-Qualitix Clinical Research Co., Ltd.   


QPS-Qualitix Clinical Research 
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    Protocol No.: CX4945-AV04-phase I 
SAP Version: 1.0 
 
 
 
 
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Page 2 of 16 
Approval of Statistical Analysis Plan 
Protocol No : CX4945-AV04-phase I 
  
The undersigned approved the SAP Version 1.0, dated 05-Jan-2023 as final. 
Programming of the tables, figures and listings based upon the specifications within this document 
can proceed.  
 
 
 
Senhwa Biosciences, Inc. Approval: 
 
 
 
 
 
 
Jin-Ding Huang 
 
 
Signature (CEO) 
 
Print Name 
 
Date 
 
 
 
 
 
QPS-Qualitix Approval: 
 
 
 
 
 
 
Jo Chen 
 
 
Signature (Lead Statistician) 
 
Print Name 
 
Date 
 
 
 
 
 
Please Note: 
QPS-Qualitix will not notify Senhwa Biosciences, Inc. of minor modifications (e.g. modification of 
column or title) of tables, listings or figures that are different from SAP when generating data-driven 
tables, listings or figures after database lock.  
 
 
 
 


QPS-Qualitix Clinical Research 
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TABLE OF CONTENTS 
1. 
INTRODUCTION .............................................................................................................. 5 
2. 
STUDY OBJECTIVE ........................................................................................................ 5 
PRIMARY OBJECTIVE ............................................................................................................ 5 
SECONDARY OBJECTIVES...................................................................................................... 5 
3. 
STUDY DESIGN ................................................................................................................ 5 
3.1 SUMMARY OF STUDY DESIGN ......................................................................................... 5 
3.2 SCHEDULE OF ACTIVITIES ............................................................................................... 6 
TABLE 1: SCHEDULE OF ACTIVITIES ..................................................................................... 6 
3.3 ENDPOINTS ..................................................................................................................... 7 
3.4 DATA MONITORING COMMITTEE (DMC) ........................................................................ 8 
4. 
GENERAL STATISTICAL ISSUES ................................................................................ 8 
4.1 CONTINUOUS ENDPOINTS ................................................................................................ 8 
4.2 CATEGORICAL ENDPOINTS .............................................................................................. 8 
4.3 SAMPLE SIZE ESTIMATION ............................................................................................... 9 
5. 
DATA HANDLING PROCEDURES ................................................................................ 9 
5.1 CODING SYSTEM ............................................................................................................. 9 
5.2 MISSING DATA HANDLING .............................................................................................. 9 
6. 
ANALYSIS OF STUDY POPULATIONS ....................................................................... 9 
INTENT-TO-TREAT (ITT) POPULATION .................................................................................. 9 
PER-PROTOCOL (PP) POPULATION ........................................................................................ 9 
SAFETY POPULATION ............................................................................................................ 9 
7. 
DISPOSITION OF PATIENTS AND STUDY COMPLETION .................................. 10 
8. 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS .................... 10 
8.1 DEMOGRAPHICS AND BASELINE CHARACTERISTICS ..................................................... 10 
8.2 MEDICAL HISTORY ....................................................................................................... 10 
8.3 CONCOMITANT MEDICATION ........................................................................................ 10 
8.4 ANTI-SARS-COV2 ....................................................................................................... 11 
8.5 SEROLOGY .................................................................................................................... 11 
9. 
EXTENT OF EXPOSURE AND DRUG COMPLIANCE ........................................... 11 
9.1 STUDY DRUG ADMINISTRATION.................................................................................... 11 
10. 
SAFETY ANALYSIS ....................................................................................................... 11 
10.1 ADVERSE EVENTS ....................................................................................................... 11 


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10.2 CLINICAL LABORATORY TESTS ................................................................................... 13 
10.3 VITAL SIGNS ............................................................................................................... 13 
10.4 12-LEAD ELECTROCARDIOGRAM (ECG) .................................................................... 13 
10.5 PHYSICAL EXAMINATION ............................................................................................ 13 
11. 
COMPUTER METHODS ............................................................................................... 14 
APPENDIX A TABLE OF CONTENTS OF LISTING ................................................................ 14 
APPENDIX B TABLE OF CONTENTS OF TABLE ................................................................... 14 
 
 


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1. INTRODUCTION 
This statistical analysis plan (SAP) is based on protocol CX4945-AV04-phase I Version 1.0 dated 30-
August-2022 and protocol clarification letter #01 dated 27-December-2022. The SAP provides details 
of data handling procedures, statistical analysis methods for safety evaluations. It also outlines 
statistical programming specifications for tables and listings, and other details on the analyses not 
provided in the study protocol. 
2. STUDY OBJECTIVE 
Primary Objective 
⚫ 
To assess safety and tolerability of CX-4945 administered orally 200 mg QD, 200 mg BID and 
400 mg BID for continuously 5 days to healthy subjects 
Secondary Objectives 
⚫ 
To evaluate changes in blood chemistry and other health assessment 
3. STUDY DESIGN 
3.1 Summary of Study Design 
This is a phase I single center, open-label, parallel design in 30 subjects to evaluate safety and 
tolerability of CX-4945 200 mg QD, 200 mg BID and 400 mg BID doses (10 subjects in each regimen) 
for continuously 5 days in healthy subjects for dose selection. Up to approximately 30 subjects will 
be enrolled into this study. A screening evaluation will occur within 28 days prior to Day 1. A subject 
screening number will be assigned to each subject in successive order of consent signing, beginning 
with S001. At the end of screening all qualified subjects will be assigned sequentially to following 
three treatment cohorts: 
• Cohort 1: CX-4945 200 mg QD 
• Cohort 2: CX-4945 200 mg BID 
• Cohort 3: CX-4945 400 mg BID 
A subject number will be assigned to participants when they have confirmed eligible for the study on 
Day 1. Each cohort will receive a unique numeric designation, and will precede the subject number 
(e.g. at cohort 1 the first two subjects would be 01-001 and 01-002; at cohort 2 the first two subjects 
would be 02-001 and 02-002). The total duration of the treatment will be 5 days. Subjects will be 
followed up at 14 days from the start of the treatment. The total duration for each subject in the study 


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SAP Version: 1.0 
 
 
 
 
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(including the screening) will be up to 42 days. 
3.2 Schedule of Activities 
Table 1: Schedule of Activities 
Procedure/Assessments 
Screening 
Visit 
Treatment 
Follow- 
Up 
Day 
SV 
Day -28~ 0 
Day 1 
(Baseline) 
Day 3 
Day 5 
Day 6 
(EOT) 
Day 14 
Window Period 
 
within 28 days 
after SV 
 
 
 
±3 days 
Informed Consent [1] 
X 
Eligibility Evaluation [2] 
X 
Subject Demographics 
X 
Medical History [3] 
X 
Physical Examination 
X 
X 
X 
X 
X 
X 
Weight and Height 
X 
Vital Signs [4] 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
X 
Laboratory Tests: 
X 
X 
X 
X 
X 
X 
Hematology [5] 
X 
X 
X 
X 
X 
X 
Blood Biochemistry [6] 
X 
X 
X 
X 
X 
X 
Coagulation [7] 
X 
X 
X 
X 
X 
X 
Serum/Urine Pregnancy Test [8] 
X 
X 
X 
Urinalysis [9] 
X 
X 
X 
X 
X 
X 
Anti-HIV, Anti-HBV, Anti-HCV 
X 
Anti-SARS-Cov2 [10] 
X 
IP Administration 
CX-4945 200 mg QD daily (Day 1 to 
Day5) 
CX-4945 200 mg BID daily (Day 1 to 
Day5) 
CX-4945 400 mg BID daily (Day 1 to 
Day5) 


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Statistical Analysis Plan 
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Concomitant Medications 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
[1] Informed consent must be obtained prior to subject participation in any protocol-related activities that are not part of 
routine care. 
[2] Initial evaluation of subject eligibility will be performed by Investigator. Subject number will be assigned on Day1 after 
confirming the subject eligibility. 
[3] Medical history and current therapies (medications and non-medications). 
[4] Vital signs will include blood pressure, heart rate, respiration rate, SpO2, and temperature. 
[5] Hematology: Hemoglobin, Hematocrit (HCT), Red Blood Cells (RBC), White Blood Cells (WBC) with total, 
differential count,(Absolute Neutrophil Count, Absolute Lymphocytes Count, Absolute Monocytes Count, 
Absolute Eosinophils Count, Absolute Basophils Count) and platelets. 
[6] Blood biochemistry: 
• 
Hepatic function indicators: total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), total protein, albumin, lactate dehydrogenase (LDH) 
• 
Renal function indicators: BUN, Serum creatinine 
• 
Electrolytes: sodium, potassium, chloride, magnesium, phosphorus, total calcium and bicarbonate, 
• 
Other: Creatine phosphokinase (CPK), C-reactive protein (CRP), Creatine kinase-MB(CK-MB 
mass), Triglyceride, Total Cholesterol, Glucose AC, Uric Acid, γ-GT. 
[7] Coagulation: Prothrombin time (PT) and International Normalized Ratio (INR) 
[8] ONLY performed on women of childbearing potential. Pregnancy Test will be tested on screening, Day 1 prior dosing and 
Day 14. 
[9] Urine samples will be tested for color, appearance, specific gravity, pH, protein, glucose, occult blood, ketones, 
leukocyte esterase, nitrite, bilirubin, urobilinogen, and microscopic examination of urine sediment. 
[10] In response to the COVID-19 pandemic, the subject will need to follow the currently site’s policies for COVID-19 to get 
the negative results of anti-SARS-Cov2 test before admission. 
 
3.3 Endpoints 
Primary Endpoint 
To evaluate the adverse events occurring from Day 1 to Day 5 (including vital signs, physical 
findings, clinical laboratory, and electrocardiogram (ECG) results) as characterized by type, 
frequency, severity [as graded by the National Cancer Institute Common Terminology Criteria 


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for Adverse Events [CTCAE] version 5.0], timing, seriousness, and relationship to study therapy 
after administration of 200 mg QD, 200 mg BID and 400 mg BID for continuously 5 days to 
healthy subjects. 
Secondary Endpoint 
Changes in blood chemistry and other health assessments from Day 1, Day 3, Day 5, and Day 6 
morning. 
3.4 Data Monitoring Committee (DMC) 
Throughout the trial, all safety and tolerability data will be reviewed and monitored by an independent 
DMC. The composition and functions of the DMC will be governed by a charter, which will be 
described elsewhere. 
A DMC safety listing and table based on frozen cleaned data will be conducted by QPS-Qualitix. The 
DMC safety listing and table will be generated based on this SAP mock listing and table. (Refer to 
Appendix A and Appendix B)  
4. GENERAL STATISTICAL ISSUES  
In general, all summaries will be displayed by treatment group and overall, and if applicable. Unless 
otherwise noted, all summaries will be descriptive in nature and will include number of subjects (N) 
and number of events (E) if applicable. 
4.1 Continuous endpoints 
Descriptive statistics including number of observations, mean, median, standard deviation, minimum 
and maximum will be presented for the raw data as well as change from baseline. The mean and 
median will be presented with one more decimal than the original data; standard deviation will be 
presented with two more decimal than the original data; minimum and maximum values will be 
presented with the same precision as the original data. For the calculation of baseline corrected values, 
baseline is defined as the last information collected before dosing for each parameter. 
4.2 Categorical endpoints 
The count and percentages will be used to summarize the categorical data. Percentages with float will 
be presented with 2 decimals; percentages with divisible number will be presented with 0 decimal. 


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4.3 Sample size estimation 
A total of 30 subjects will be assigned sequentially into 3 cohorts in this study. The sample size is 
based on clinical judgment. No statistical power calculation is used to establish the sample size for 
this proof-of-concept study. 
5. DATA HANDLING PROCEDURES 
5.1 Coding System 
Medical coding includes AE coding, medical history coding and concomitant medication coding. AE 
coding and medical history will be coded by Medical Dictionary for Regulatory Activities (MedDRA) 
Version 25.1 or higher and concomitant medication will be coded by WHODrug Global, B3, 
September 2022 or the most updated version. The latest version before database lock (DBL) will be 
adopted for final analysis. 
5.2 Missing Data Handling 
For data listings, all raw data will be reported/ displayed exactly as provided. No imputation will be 
performed on missing data. All analyses will be performed on data available at the time point 
considered. In summary tables, the number of subjects without missing data will be presented unless 
otherwise specified. In calculations of percentages, subjects with missing data will not be considered 
in numerator of denominator unless otherwise specified. 
6. ANALYSIS OF STUDY POPULATIONS 
Intent-to-treat (ITT) Population  
The ITT population is defined as all assigned subjects who received at least one dose of study drug. 
This population will be used as the primary analysis population for analysis of the primary and 
secondary endpoints. 
Per-protocol (PP) Population 
The PP population is defined as the set of subjects who meet the ITT population requirements and are 
not associated with any major protocol violations. This population will be identified before the 
database lock. This population will be used as the supportive analysis population for analysis of the 
primary and secondary endpoints. 
Safety Population 


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The Safety population is defined as any subject receiving at least one dose of CX-4945. This 
population will be used for the analysis of safety parameters. 
Because of primary/secondary endpoint equals to safety endpoint. If the subjects included in three 
populations are the same, all analysis tables will only be presented by safety population with a 
footnote explaining that all populations are the same. Otherwise, it will be analyzed by three 
populations. 
7. DISPOSITION OF PATIENTS AND STUDY COMPLETION 
Data on date of visit will be listed in Listing 16.2.1.1. Data on the completion status and primary 
reason for study discontinuation will be listed in Listing 16.2.1.2. The subject disposition and 
completion status will be summarized by treatment group in Table 14.1.1. The subject eligibility will 
be listed in Listing 16.2.1.3. All minor and major protocol deviation(s) will be listed in Listing 16.2.2. 
All subjects who excluded from ITT, PP and safety population will be listed in Listing 16.2.3. 
8. DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS 
8.1 Demographics and Baseline Characteristics 
Subject demographics will be listed in Listing 16.2.4.1. Subject height, weight and body mass index 
(BMI) collected at screening will be listed in Listing 16.2.4.7. Demographics and baseline 
characteristics including height, weight, BMI, medical history, prior and concomitant 
medications/therapies will be analyzed with descriptive statistics and summarized for ITT, PP and 
safety population by treatment group in Table 14.1.2. 
8.2 Medical History 
Medical history will be coded by MedDRA version 25.1 or higher and listed by subject in Listing 
16.2.4.2. 
8.3 Concomitant Medication 
All concomitant medications will be coded by WHODrug Global, B3, September 2022 or the most 
updated version and listed in Listing 16.2.4.3 and be summarized by treatment group using the coded 
term and preferred name in Table 14.1.3. Concomitant non-medication therapies will be listed in 
Listing 16.2.4.4. 


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8.4 Anti-SARS-Cov2 
Subject anti-SARS-Cov2 test collected on Day 1 will be listed in Listing 16.2.4.5. 
8.5 Serology 
Clinical laboratory analyses serology test collected at Screening will be listed in Listing 16.2.4.6. 
9. EXTENT OF EXPOSURE AND DRUG COMPLIANCE 
9.1 Study Drug Administration  
The information of date and time of study drug administration will be listed in Listing 16.2.5. 
10. SAFETY ANALYSIS 
10.1 Adverse Events 
All AEs recorded in the eCRF (electronic Case Report Form) will be coded using the MedDRA 25.1 
or higher and listed in Listing 16.2.7. 
AE study day and duration will be added in the AE listings. The following calculations and derivations 
will be used, making the most conservative judgment. 
➢ 
For study day of AE as “XX” or “Prior”:  
 
Study day = AE onset date - date of prior administration + 1. 
 
If AE onset date is prior to date of first administration, then the study day will be “Prior”.  
 
If onset date is unknown, study day will be missing.  
➢ 
For duration of AE as “XXDXXHXXM”:  
 
Duration = resolution date and time of the event minus onset date and time of the event.  
 
If onset or resolution time unknown, then the duration will be calculated based on resolution 
date and onset date only, and plus 1.  
 
If onset or resolution date is unknown, duration will be missing. 
Treatment Emergent AE’s (TEAE) are defined as events with an onset on or after the first treatment.  
As defined in the eCRF, all AEs will be assigned a severity of: Grade 1 (Mild), Grade 2 (Moderate), 
Grade 3 (Severe or medically significant but not immediately life-threatening), Grade 4 (Life-
threatening consequences) or Grade 5 (Death related to AE). All AEs will be classified as either 


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related or unrelated to study drug. A study drug-related AE is defined as any TEAE that is assessed 
to have ‘Possibly Related’, ‘Probably Related’ or ‘Definitely Related’ relationship to study drug. An 
AE not related to study drug is defined as any AE that is assessed as ‘Unrelated’ or ‘Unlikely Related’ 
to study drug. 
Frequency counts will be tabulated and displayed by the MedDRA primary system organ class (SOC) 
and preferred term (PT) by group and overall.  
A general summary of all TEAEs and serious TEAEs will be provided in Table 14.3.1.1. This 
summary will present the event numbers, subject numbers, and subject percentages according to the 
following categories: 
⚫ 
Subject with Any TEAE 
⚫ 
Subject with Any TESAE 
⚫ 
Subject with Any Drug-Related TEAE 
⚫ 
Severity 
⚫ 
Was This a SAE? 
⚫ 
Action Taken with Study Drug 
⚫ 
Treatment Required 
⚫ 
Relationship to Study Drug 
⚫ 
Outcome 
Other summary tables for TEAEs will include: 
⚫ 
Table 14.3.1.2: Treatment-Emergent Adverse Events - MedDRA 
⚫ 
Table 14.3.1.3: Treatment-Emergent Adverse Events - MedDRA (Preferred Term over XX % 
in Any Treatment Group) 
⚫ 
Table 14.3.1.4: Treatment-Emergent Adverse Events by Severity - MedDRA 
⚫ 
Table 14.3.1.5: Treatment-Emergent Adverse Events by Relationship to Study Drug - 
MedDRA 
⚫ 
Table 14.3.1.6: Treatment-Emergent Adverse Events by Action Taken with Study Drug - 
MedDRA 
⚫ 
Table 14.3.1.7: Treatment-Emergent Serious Adverse Events by Severity - MedDRA 
⚫ 
Table 14.3.1.8: Treatment-Emergent Serious Adverse Events by Relationship to Study Drug - 
MedDRA 
⚫ 
Table 14.3.1.9: Treatment-Emergent Serious Adverse Events by Action Taken with Study Drug 
- MedDRA 
⚫ 
Table 14.3.2.1: Listing of Subjects with Treatment-Emergent Serious Adverse Events 


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⚫ 
Table 14.3.2.2: Listing of Subjects with Treatment-Emergent Adverse Events Leading to 
Premature Discontinuation 
⚫ 
Table 14.3.2.3: Listing of Subjects with Treatment-Emergent Adverse Events Leading to Death 
10.2 Clinical Laboratory Tests 
Clinical laboratory analyses including hematology, blood biochemistry, urinalysis, microscopic exam, 
coagulation and serum/urine pregnancy test will be listed in Listing 16.2.8.1 through Listing 16.2.8.6. 
All abnormal laboratory values and evaluation flags ‘NCS’ (not clinically significant) or ‘CS’ 
(clinically significant) will be listed in Table 14.3.4.  
The observed results and the mean change from baseline of hematology, blood biochemistry, 
urinalysis and coagulation will be summarized by each testing parameter, each visit and group in 
Table 14.3.5.1 through Table 14.3.5.4. The shift tables of hematology, blood biochemistry and 
urinalysis will be provided by each testing parameter, post baseline visit and group in Table 14.3.5.5 
through Table 14.3.5.8.  
For any laboratory results reported as “<limit of quantification (<LLOQ)”, the numeric value used 
for summary will be the half of LOQ value. For results reported as “>limit of quantification 
(>ULOQ)”, the numeric value used for summary will be the LOQ value plus one unit of the minimum 
digits of the parameter. For example, if the results is “> 2”, the numeric value will be 2 plus 1 which 
is 3; if the results is “< 0.5”, the numeric value will be half of 0.5 which is 0.25. 
10.3 Vital Signs  
Vital signs will be listed in Listing 16.4.1. The observed vital signs and the mean change from baseline 
over each visit will be analyzed with descriptive statistics and summarized by group in Table 14.3.6. 
10.4 12-Lead Electrocardiogram (ECG) 
12-lead ECG will be listed in Listing 16.4.2. The observed 12-lead ECG and the mean change from 
baseline over each visit will be analyzed with descriptive statistics and summarized by group in Table 
14.3.7. 
10.5 Physical Examination 
Physical examination will be listed in Listing 16.4.3. The counts and percentage of physical 
examination will be summary by group in Table 14.3.8. 


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11. COMPUTER METHODS 
All statistical analyses will be conducted using SAS® software, Version 9.4 of the SAS System for 
Windows 10. Copyright© 2016 SAS Institute Inc. SAS and all other SAS Institute Inc. product or 
service names are registered trademarks or trademarks of SAS Institute Inc., Cary, NC, USA. 
APPENDIX A TABLE OF CONTENTS OF LISTING 
Section 
Title 
Included 
in DMC 
Listing 16.2.1.1 
Subject Disposition (Date of Visit) 
V 
Listing 16.2.1.2 
Subject Disposition (Completion Status) 
V 
Listing 16.2.1.3 
Subject Eligibility 
 
Listing 16.2.2 
Protocol Deviation List 
V 
Listing 16.2.3 
Subjects Excluded from Analysis 
 
Listing 16.2.4.1 
Individual Subject Demographics 
V 
Listing 16.2.4.2 
Medical History 
 
Listing 16.2.4.3 
Prior and Concomitant Medications 
V 
Listing 16.2.4.4 
Non Medication Therapy 
V 
Listing 16.2.4.5 
Clinical Laboratory Tests - Anti-SARS-Cov2 
V 
Listing 16.2.4.6 
Clinical Laboratory Tests - Serology 
V 
Listing 16.2.4.7 
Individual Subject Height and Weigh 
 
Listing 16.2.5 
Study Drug Administration 
V 
Listing 16.2.7 
Individual Subject Adverse Events 
V 
Listing 16.2.8.1 
Clinical Laboratory Tests - Hematology 
V 
Listing 16.2.8.2 
Clinical Laboratory Tests - Blood Biochemistry 
V 
Listing 16.2.8.3 
Clinical Laboratory Tests - Urinalysis 
V 
Listing 16.2.8.4 
Clinical Laboratory Tests - Microscopic Exam 
V 
Listing 16.2.8.5 
Clinical Laboratory Tests - Coagulation 
V 
Listing 16.2.8.6 
Clinical Laboratory Tests - Serum/Urine Pregnancy Test 
V 
Listing 16.4.1 
Individual Subject Vital Signs 
V 
Listing 16.4.2 
Individual Subject 12-Lead Electrocardiogram (ECG) 
V 
Listing 16.4.3 
Individual Subject Physical Examination 
V 
 
APPENDIX B TABLE OF CONTENTS OF TABLE 


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Section 
Title 
Included 
in DMC 
Table 14.1.1 
Summary of Subject Disposition 
V 
Table 14.1.2 
Summary of Subjects Demographics and Baseline Characteristics 
V 
Table 14.1.3 
Summary of Prior and Concomitant Medications - WHODrug 
 
Table 14.3.1.1 
Treatment-Emergent Adverse Events 
V 
Table 14.3.1.2 
Treatment-Emergent Adverse Events - MedDRA 
V 
Table 14.3.1.3 
Treatment-Emergent Adverse Events - MedDRA (Preferred Term 
over 10 % in Any Treatment Group) 
V 
Table 14.3.1.4 
Treatment-Emergent Adverse Events by Severity - MedDRA 
V 
Table 14.3.1.5 
Treatment-Emergent Adverse Events by Relationship to Study 
Drug - MedDRA 
V 
Table 14.3.1.6 
Treatment-Emergent Adverse Events by Action Taken with Study 
Drug - MedDRA 
V 
Table 14.3.1.7 
Treatment-Emergent Serious Adverse Events by Severity - 
MedDRA 
V 
Table 14.3.1.8 
Treatment-Emergent Serious Adverse Events by Relationship to 
Study Drug - MedDRA 
V 
Table 14.3.1.9 
Treatment-Emergent Serious Adverse Events by Action Taken 
with Study Drug - MedDRA 
V 
Table 14.3.2.1 
Listing of Subjects with Treatment-Emergent Serious Adverse 
Events 
V 
Table 14.3.2.2 
Listing of Subjects with Treatment-Emergent Adverse Events 
Leading to Premature Discontinuation 
V 
Table 14.3.2.3 
Listing of Subjects with Treatment-Emergent Adverse Events 
Leading to Death 
V 
Table 14.3.4 
Abnormal Laboratory Values 
V 
Table 14.3.5.1 
Laboratory Values Over Time - Hematology 
V 
Table 14.3.5.2 
Laboratory Values Over Time - Blood Biochemistry 
V 
Table 14.3.5.3 
Laboratory Values Over Time - Urinalysis 
V 
Table 14.3.5.4 
Laboratory Values Over Time - Coagulation 
V 
Table 14.3.5.5 
Individual Subject Changes (Shift Table) - Hematology 
V 
Table 14.3.5.6 
Individual Subject Changes (Shift Table) - Blood Biochemistry 
V 
Table 14.3.5.7 
Individual Subject Changes (Shift Table) – Urinalysis 
V 
Table 14.3.5.8 
Individual Subject Changes (Shift Table) - Coagulation 
V 


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Table 14.3.6 
Summary of Vital Signs 
V 
Table 14.3.7 
Summary of 12-Lead Electrocardiogram (ECG) 
V 
Table 14.3.8 
Summary of Physical Examination 
V