A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Renal Dialysis Patients
Phase: PHASE2
Conditions: COVID-19
Sponsor: William B. Ershler, MD

Clinical Study Protocol: Ta1 to Prevent COVID-19 Infection in Elderly Renal Dialysis Patients  
 
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Clinical Study Protocol 
 
Protocol Title: 
A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in 
Elderly Renal Dialysis Patients  
Investigational Drug: 
ZADAXIN® (thymalfasin/Ta1) Lyophilisate for Solution for Injection 
Principal Investigator: 
William B. Ershler, MD 
Director, Benign Hematology 
Inova Schar Cancer Institute 
Inova Fairfax Hospital 
8081 Innovation Park Drive 
Fairfax, VA 22031 
 
Phone 571-472-1069 
Fax     571-472-1391 
william.ershler@inova.org 
Co-Investigators 
Franco Musio, MD 
Abdus Salam, MD, PhD 
Research Nurse 
TBA 
Trial Coordinator 
Musirah Khan, MD 
Pharmacist 
TBA 
Statistician 
Pramita Bagchi, PhD 
Jiayang Sun, PhD 
Consultants 
 
Allan L. Goldstein, PhD 
Cynthia Tuthill, PhD 
 
 
 
Date: 
17 April 2020 

Clinical Study Protocol: Ta1 to Prevent COVID-19 Infection in Elderly Renal Dialysis Patients 
 
  
 
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1 
INVESTIGATOR AGREEMENT SIGNATURE PAGE 
Protocol Title: A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Elderly 
Renal Dialysis Patients 
Original Protocol Issue Date: 17 April 2020 
I have read the attached protocol and appendices dated 5 April 2020 and agree to abide by all 
provisions set forth therein. I will provide copies of the protocol and other pertinent information 
to all individuals responsible to me who will assist with the study. 
I agree to comply with the International Conference on Harmonisation Tripartite Guideline on 
Good Clinical Practice and applicable FDA regulations/guidelines set forth in 21 Code of Federal 
Regulations Parts 11, 50, 54, 56, and 312. 
Before study initiation, during the study if there are changes that affect my financial disclosure 
status, and after the study is completed, I agree to ensure that Financial Disclosure Statements 
will be completed by: 
• 
Myself and dependent children 
• 
My Subinvestigators (including, if applicable, their spouses [or legal partners] and dependent 
children) 
                    17 April 2020 
_____________________________         _______________________ 
Signature of Principal Investigator         Date (DD MONTH YYYY) 
__________________________________________ 
William B. Ershler, MD 
 
 
 

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2 
PROTOCOL SYNOPSIS 
Product: 
ZADAXIN® (thymalfasin/Ta1) lyophilisate for solution for 
injection 
Title of Study: 
A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 
Infection in Elderly Renal Dialysis Patients 
Phase of Development: 
Pilot Study 
Background and Rationale: 
Ta1 is a naturally occurring peptide with immunomodulatory 
activities. ZADAXIN® Ta1 is a synthetic version currently 
approved for use in 37 countries; in particular it is approved 
in China hepatitis B and to enhance vaccine response. Ta1 
has also been studied in multiple clinical trials in the United 
States. Ta1 has been used clinically in pilot studies for 
treatment of SARS and other lung infections including acute 
respiratory disease (ARD) and chronic obstructive pulmonary 
disorder (COPD), as well as infections after bone marrow 
transplant. The beneficial clinical effects of Ta1 result from 
activation of toll-like receptor (TLR) 9 in dendritic and other 
immune system cells, resulting in augmentation of T helper 
(Th1) function, natural killer (NK) cell activity, and increased 
antibody responses to T-cell dependent antigens. Importantly, 
Ta1 also leads to an increase in IL-10 producing regulatory T 
cells, which create feedback inhibition of cytokine 
production, hence dampening immune response and 
preventing a pro-inflammatory cytokine storm. 
Based on post-marketing treatment experience of more than 
600,000 patients, Ta1 has been well tolerated. Ta1 has been 
administered to elderly subjects (up to 101 years old), 
children (as young as 13 months), and immunocompromised 
patients. The most common adverse events in previous 
clinical trials include injection-site pain (such as burning and 
itching) which was mild and lasted for less than 30 minutes, 
as well as fever, nausea, and flu-like symptoms which were 
mild to moderate in severity. Thus, while Ta1 is one of only a 
few immunomodulatory agents that have been approved for 
human use, it does not appear to induce most of the side 
effects and toxicities commonly associated with other 
biological response modifiers (BRMs) in this class, such as 
interferon and interleukin-2. 
The actual dose, frequency, and length of treatment with Ta1 
have differed depending upon the indication, ranging from 
1.6 mg twice a week for up to 12 months; 1.6 mg twice a day 

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for several weeks; 6.4 mg daily, 4 days a week, for 2 weeks 
out of every month up to 6 months in duration; and 16 mg 
twice a week for four weeks, with few adverse events 
observed. The proposal to evaluate Ta1 at a dose of 1.6 mg is 
based on previous studies which have shown an increase in 
dose above 1.6 mg to show little, if any, improvement in 
response. 
Patients with end-stage renal disease (ESRD) on 
hemodialysis, in addition to their intrinsic kidney disease and 
frequent burden of comorbidities, also have increased risk of 
exposure to communicable diseases as they are treated 
several times each week at hemodialysis centers with several 
other patients and clinic staff in attendance. The majority of 
patients are over 60 years of age and many are receiving 
immunosuppressive medications. Accordingly, ESRD 
patients are particularly susceptible to COVID-19 infection. 
Ta1 has been shown to be safely administered to 
hemodialysis patients on a similar schedule to that proposed 
below, and was efficacious in enhancing influenza vaccine 
responses [1]. 
Objectives: 
Primary Objective 
To demonstrate that Ta1 administered twice weekly for eight 
weeks to renal dialysis patients 60 years and older will reduce 
the incidence of COVID-19 infection compared with a 
similar population of patients who do not receive Ta1. 
Secondary Objectives 
1.    To demonstrate that renal dialysis patients treated with 
Ta1 who become infected with COVID-19 will have a milder 
course of infection in terms of hospitalization rate, 
requirement (length) for ICU stay, requirement for 
mechanical ventilation, and survival than renal dialysis 
patients not treated with Ta1. 
2.    To demonstrate a decrease in hospitalization rates in 
renal dialysis patients treated with Ta1 who are not infected 
with COVID-19 compared to those not treated with Ta1. 
Study Design: 
It is our hypothesis that a course of Ta1 administered to 
individuals at high risk for COVID-19 infection will reduce 
the rate of infection (primary objective) and severity of 
infection (secondary objective) with COVID-19, compared to 
untreated individuals in the same hemodialysis units with 

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comparable risk. The secondary objectives also include an 
evaluation of the need for hospitalization in those patients 
who do not become infected with COVID-19.  
Ideally, a randomized clinical trial with placebo control 
would be a preferred approach to address this hypothesis. 
However, the urgency of the current situation necessitates a 
simpler research design and implementation. Accordingly, 
we consider this a pilot study from which meaningful clinical 
data may rapidly be apparent.   
After screening, renal dialysis patients 60 years and older 
who meet the inclusion criteria will receive Ta1 (1.6 mg) 
administered subcutaneously (SC) twice weekly for eight 
weeks.  Individuals in the control arm will be followed on the 
identical protocol but will not receive twice weekly Ta1. 
After the treatment period, all subjects will be followed for 
efficacy outcomes for an additional 4 months.  
Sample Size: 
A total of up to 240 patients will be enrolled 
Countries: 
U.S. 
Study Period: 
 
Once FDA and IRB approval are obtained, the research team 
will promptly initiate the process of subject recruitment. 
Recruitment of all subjects will be completed in four months 
and the observation phase in one year. 
Diagnosis and Main Criteria 
for Inclusion: 
1. Age 60 or greater 
2. Signed informed consent 
3. End-stage renal disease (ESRD) who receive 
hemodialysis 2 or more times each week and are expected 
to continue on dialysis indefinitely. 
Main Exclusion Criteria:  
1. Patients on short-term hemodialysis, such as those with 
transient renal dysfunction associated with acute illness 
who are projected to have return in renal function 
2. Patients for whom renal transplantation is anticipated 
within the next six months 
3. Patients with an anticipated survival of less than 3 
months 
4. Patients with symptoms that might be attributable to 
COVID-19 infection (see Appendix 1 for symptom 
questionnaire) 
5. Patients who test positive for SARS-CoV2 

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6. Patients with active infectious disease requiring 
antibiotics  
7. Patients with hospitalization within the previous 3 
months for acute myocardial infarction or congestive 
heart failure 
8. Patients with advanced malignancy receiving cytotoxic 
chemotherapy 
9. Patients with a Karnofsky Performance Scale score of 
less than 60 
10. Patients with prior history of solid organ (kidney, liver, 
heart, lung, pancreas) or bone marrow transplant 
11. Patients with active autoimmune disease on 
immunosuppressive medication 
12. Patients receiving Plaquenil 
13. Participation in an investigational drug or device trial in 
previous 30 days 
14. History of allergy or intolerance to Ta1 
15. Any other medical or psychiatric condition that, in the 
opinion of the Investigator, would compromise patient 
safety or interfere with the objectives of the protocol or 
completion of the protocol treatment. 
Drug Formulation: 
Ta1 is contained, stored, and dispensed from individual 
tamper-proof glass vials with 1.6 mg Ta1 as a lyophilized 
cake containing 5% mannitol, buffered with phosphate to pH 
6.4-7.3. Vials are reconstituted with 1 mL of supplied diluent 
(sterile Water for Injection), prior to subcutaneous 
administration. 
Dose and Mode of 
Administration: 
Active arm: 1.6 mg Ta1 in 1 mL SC injection twice weekly 
after dialysis 
Duration of Treatment: 
8 weeks 
Reference Therapy, Dose 
and Mode of 
Administration: 
Control arm: standard care  
Duration of Treatment: 
8 weeks 
Randomization: 
Patients will be randomized 1:1 
Randomization will be stratified by site 
Efficacy Endpoints: 
Primary Efficacy Endpoint 

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The primary efficacy endpoint is reduction in documented 
infection with COVID-19. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
1. Need for hospitalization  
2. Hospital length of stay 
3. ICU admission  
4. ICU length of stay 
5. Mechanical ventilation 
6. Duration of mechanical ventilation 
7. Recovery time from COVID-19  
8. Change in any existing comorbidities (e.g., worsening 
congestive heart failure) or occurrence of newly 
diagnosed disease  
9. Incidence of non-COVID-19 infections (other respiratory, 
urinary tract, cellulitis, etc.)  
10. Change in T lymphocyte subsets (CD4, CD8)  
11. Mortality 
 
Safety Endpoints: 
Adverse events, vital signs, and laboratory parameters 
 

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3 
TABLE OF CONTENTS 
1 INVESTIGATOR AGREEMENT SIGNATURE PAGE .........................................................2 
2 PROTOCOL SYNOPSIS ..........................................................................................................3 
Primary Efficacy Endpoint .....................................................................................................6 
Secondary Efficacy Endpoints ...............................................................................................7 
3 TABLE OF CONTENTS ...........................................................................................................8 
4 ABBREVIATIONS .................................................................................................................10 
5 INTRODUCTION AND STUDY RATIONALE ...................................................................11 
5.1 Introduction .................................................................................................................11 
5.2 Background and Rationale ..........................................................................................11 
6 OBJECTIVES ..........................................................................................................................13 
6.1 Primary Objective .......................................................................................................13 
6.2 Secondary Objectives ..................................................................................................13 
7 STUDY DESIGN.....................................................................................................................13 
8 ENDPOINTS ...........................................................................................................................15 
8.1 Primary Endpoint ........................................................................................................15 
8.2 Secondary Efficacy Endpoints ....................................................................................15 
8.3 Safety Endpoints .........................................................................................................15 
9 STUDY POPULATION ..........................................................................................................16 
9.1 Sample Size .................................................................................................................16 
9.2 Inclusion Criteria .........................................................................................................16 
9.3 Exclusion Criteria ........................................................................................................16 
9.4 Removal of Subjects ....................................................................................................16 
10 STUDY TREATMENT .........................................................................................................17 
10.1 Treatment Plan ..........................................................................................................17 
10.2 Identity of Clinical Trial Material .............................................................................17 
10.3 Labeling and Packaging ............................................................................................18 
10.4 Study Drug Accountability ........................................................................................18 
10.5 Method of Assigning Subjects to Treatment .............................................................18 
10.6 Selection of Doses .....................................................................................................18 
10.7 Concomitant Therapy ................................................................................................19 
10.8 Standard of Care ........................................................................................................19 
11 ASSESSMENTS ....................................................................................................................19 
11.1 Efficacy Assessments ................................................................................................19 
11.2 Safety Assessments ...................................................................................................20 
12 STUDY PROCEDURES .......................................................................................................21 

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12.1 Schedule of Events ....................................................................................................21 
12.2 Screening ...................................................................................................................21 
12.3 Weekly Study Procedures (for 8 weeks) ...................................................................21 
12.4 Every Other Week Study Procedures (for 8 weeks) .................................................22 
12.5 Additional Blood Draws at Week 4, Week 8 ............................................................22 
12.6 Additional Procedures if respiratory infection symptoms are seen ...........................22 
12.7 Monthly Follow-up Visits (for 4 months) .................................................................22 
13 ADVERSE EVENT REPORTING ........................................................................................23 
13.1 Adverse Event Definition ..........................................................................................23 
13.2 Assessing Severity of Adverse Events ......................................................................23 
13.3 Assessing Relationship of Adverse Event to Study Treatment .................................24 
13.4 Recording of Adverse Events ....................................................................................24 
13.5 Adverse Event Recording Period ..............................................................................24 
13.6 Serious Adverse Event Definition .............................................................................24 
13.7 Serious Adverse Event Recording Period .................................................................25 
13.8 Regulatory Reporting of Adverse Events ..................................................................25 
13.9 Data Safety Monitoring Board (DSMB) ...................................................................25 
14 DATA MANAGEMENT .......................................................................................................25 
15 STATISTICAL ANALYSIS .................................................................................................25 
15.1 Sample size justification ............................................................................................25 
15.2 Data analysis plan ......................................................................................................27 
16 ETHICS..................................................................................................................................27 
16.1 Good Clinical Practice ..............................................................................................27 
16.2 Institutional Review Board ........................................................................................27 
16.3 Subject Information and Informed Consent ..............................................................28 
16.4 Financial Disclosure by Investigators .......................................................................28 
16.5 Archiving and Data Retention ...................................................................................28 
16.6 Confidentiality ...........................................................................................................28 
17 REFERENCES ......................................................................................................................29 
18 APPENDIX 1 .........................................................................................................................32 
 
 
 
 

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4 
ABBREVIATIONS 
Abbreviation 
Full Term 
ADL 
activities of daily living 
AE 
adverse event 
ARDS 
acute respiratory disease 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CMV 
cytomegalovirus  
COPD 
chronic obstructive pulmonary disorder 
CRF 
case report form 
CRP 
C-reactive protein 
CTM 
clinical trial material (i.e., ZADAXIN or placebo) 
ESRD 
end-stage renal disease 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation  
ICU 
intensive care unit 
IL 
interleukin 
IND 
investigational new drug 
IRB 
Institutional Review Board 
LDH 
lactate dehydrogenase 
mL 
milliliter 
mg 
milligram 
2019-nCoV 
2019 novel coronavirus 
NK 
natural killer 
NOEL 
no observable effect level 
SAE 
serious adverse event 
SARS 
severe actute respiratory syndome 
SC 
subcutaneous(ly) 
Ta1 
ZADAXIN thymalfasin, thymosin alpha 1 
Th1 
Th1-type T cell 
TLR 
Toll-like receptor 
WHO 
World Health Organization 

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5 
INTRODUCTION AND STUDY RATIONALE 
5.1 
Introduction  
In December of 2019 a cluster of unexplained pneumonia cases were reported in Wuhan, China. 
Shortly thereafter, the causative agent of this mysterious pneumonia was identified as a novel 
coronavirus [2]. On January 12, 2020 the World Health Organization (WHO) temporarily named 
this new virus the 2019 novel coronavirus (2019-nCoV) and later named it severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2).  In February 2020 the term COVID-19 was 
introduced as the name of the disease caused by SARS-CoV-2. The COVID-19 epidemic has 
now reached pandemic proportion and spread beyond China prominently throughout the world 
including Asia, Europe, United States and over 150 sovereign nations [3-5].  COVID-19 causes a 
respiratory illness characterized initially by sore throat, fever, cough and malaise but progressing 
in some patients to lower respiratory infection, respiratory failure and mortality [6]. COVID-19 
is highly contagious and it has been projected that as many as 40% of the entire United States 
population may become infected [7, 8]. One thing that has become increasingly clear is that older 
individuals, and particularly those with comorbidities and/or immunosuppression are at 
particularly high risk for adverse outcomes including requiring hospitalization, intensive care 
management, ventilatory support and mortality [9].    
With the current and rapidly expanding burden of infection in the United States there has been 
great emphasis on disease treatment as well as vaccine development. Indeed, already there are 
clinical trials of antivirals and/or antimalarials that are currently enrolling patients. Vaccines are 
also on the fast track for development but it has been projected that their availability will be at 
least 12-18 months from now.   
As we await the availability of an effective vaccine, we propose the investigation of an immune 
enhancing synthetic peptide with established safety and efficacy in a variety of clinical situations 
in the context of viral disease. This study should demonstrate feasibility and possibly provide 
evidence of efficacy. Further, our findings may be particularly valuable once a COVID-19 
vaccine is available.  At that time there may be efforts to enhance vaccine efficacy among at risk 
populations, such as in patients of advanced age or with comorbidities.  Thymalfsin (thymosin 
alpha 1 or Ta1), the subject for this research protocol, is also known to provide increased 
response to vaccines. In previously published Phase 2 clinical trials carried out in the United 
States in over 400 geriatric (66 to 99 years) and kidney dialysis patients, Ta1 was reported to 
safely and significantly increase antibody responses to the influenza vaccine and reduce 
symptoms of influenza following infection [1, 10, 11]. 
5.2 
Background and Rationale 
Ta1 is a naturally occurring peptide that has been evaluated for its immunomodulatory activities 
and related therapeutic potential in several conditions and diseases, including infectious disease 
and cancer. ZADAXIN® brand Ta1 is a synthetic version currently approved for use in 37 
countries; in particular it is approved in China hepatitis B and to enhance vaccine response. 
Notably, Ta1 has been used clinically in pilot studies for treatment of severe acute respiratory 
syndome (SARS) [12] and other lung infections including acute respiratory distress syndrome 

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(ARDS) [13] and chronic obstructive pulmonary disorder (COPD) [14], as well as infections 
after bone marrow transplant [15]. Larger clinical trials have shown significant efficacy for 
treatment of severe sepsis [16, 17] and hepatitis B [18], along with certain cancers such as 
melanoma, hepatocellular, and lung cancer [19]. Ta1 has also demonstrated improvement in 
response to vaccines in the elderly and in patients immunocompromised by renal disease. The 
beneficial clinical effects of Ta1 result from activation of toll-like receptor (TLR) 9 in dendritic 
and other immune system cells, resulting in augmentation of T helper (Th1) function, natural 
killer (NK) cell activity, and increased antibody responses to T-cell dependent antigens. 
Importantly, Ta1 also leads to an increase in IL-10 producing regulatory T cells, which create 
feedback inhibition of cytokine production, hence dampening immune response and preventing a 
pro-inflammatory cytokine storm. 
Based on post-marketing treatment experience of more than 600,000 patients, Ta1 has been well 
tolerated. Ta1 has been administered to elderly subjects (up to 101 years old), children (as young 
as 13 months), and immunocompromised patients. The most common adverse events in previous 
clinical trials include injection-site pain (such as burning and itching) which was mild and lasted 
for less than 30 minutes, as well as fever, nausea, and flu-like symptoms which were mild to 
moderate in severity. Thus, while Ta1 is one of only a few immunomodulatory agents that have 
been approved for human use, it does not appear to induce most of the side effects and toxicities 
commonly associated with other biological response modifiers (BRMs) in this class, such as 
interferon and interleukin-2. 
The actual dose, frequency, and length of treatment with Ta1 have differed depending upon the 
indication, ranging from 1.6 mg twice a week for up to 12 months; 1.6 mg twice a day for several 
weeks; 6.4 mg daily, 4 days a week, for 2 weeks out of every month up to 6 months in duration; 
and 16 mg twice a week for four weeks, with few adverse events observed. The proposal to 
evaluate Ta1 at a dose of 1.6 mg is based on previous studies which have shown an increase in 
dose above 1.6 mg to show little, if any, improvement in response. 
Patients with end-stage renal disease (ESRD) on hemodialysis, in addition to their intrinsic 
kidney disease and frequent burden of comorbidities [20], also have increased risk of exposure to 
communicable diseases as they are treated several times each week at hemodialysis centers with 
several other patients and clinic staff in attendance. The majority of patients are over 60 years of 
age and many are receiving immunosuppressive medications. Accordingly, ESRD patients are 
particularly susceptible to COVID-19 infection. Ta1 has been shown to be safely administered to 
hemodialysis patients on a similar schedule to the one proposed below, and was efficacious in 
enhancing (> 4fold) the antibody responses to the influenza vaccine in geriatric & renal dialysis 
patients [1].  
 
 
 
 

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6 
OBJECTIVES 
6.1 
Primary Objective 
Primary Objective 
To demonstrate that Ta1 administered twice weekly after dialysis for eight weeks to renal 
dialysis patients 60 years and older will reduce the incidence of COVID-19 infection over a six-
month period compared with a similar population of patients who do not receive Ta1. 
6.2 
Secondary Objectives 
Secondary Objectives: 
1.    To demonstrate that renal dialysis patients 60 years and older treated with Ta1 who become 
infected with COVID-19 will have a milder course of infection in terms of hospitalization rate, 
requirement for and length of ICU stay, requirement for mechanical ventilation, and survival 
than renal dialysis patients not treated with Ta1. 
2.    To demonstrate a decrease in hospitalization rates in renal dialysis patients treated with Ta1 
who are not infected with COVID-19 compared to those not treated with Ta1. 
7 
STUDY DESIGN 
It is our hypothesis that a course of Ta1 administered to individuals at high risk for COVID-19 
infection (hemodialysis patients 60 years and older) will reduce the rate of COVID-19 infection 
(primary objective) and severity of infection (secondary objective) with COVID-19, compared to 
untreated individuals in the same hemodialysis units with comparable risk. The secondary 
objectives also include an evaluation of the need for hospitalization in those patients who do not 
become infected with COVID-19.  
Ideally, a randomized clinical trial with placebo control would be a preferred approach to address 
this hypothesis. However, the urgency of the current situation necessitates a simpler research 
design and implementation. Accordingly, we consider this a pilot study from which meaningful 
clinical data may rapidly be apparent.   
After screening, renal dialysis patients 60 years and older who meet the inclusion criteria will 
receive Ta1 (1.6 mg) administered SC twice weekly for eight weeks.  Individuals in the control 
arm will be followed on the identical protocol but will not receive twice weekly Ta1. After the 
treatment period, all subjects will be followed for efficacy outcomes for an additional 4 months. 
The total duration of the trial will be 1 year, including the estimated time required for screening. 
A schema outlining the study design is presented in Figure 1. 
 
 

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Figure 1: 
Study Design Schema 
 
 
 
Hemodialysis patients 60 
years and older 
 
 
 
 
 
Screening:  confirmation of 
eligibility (evaluation of 
inclusion/exclusion criteria 
and confirmation via 
clinical coordinating center) 
 
 
 
 
 
Randomization (1:1) 
 
 
 
 
Ta1 (1.6 mg SC twice weeky) 
Clinical and laboratory assessments 
at 2 week intervals  
8 weeks 
 
 
No Ta1 treatment 
Clinical and laboratory assessments 
at 2 week intervals  
8 weeks 
 
 
 
 
Clinical and laboratory 
assessments once a month 
for 4 months 
 
 
 
 

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8 
ENDPOINTS 
8.1 
Primary Endpoint 
The primary efficacy endpoint is reduction in documented infection with COVID-19. This is 
defined as clinical suspicion (presence of symptoms of respiratory infection; see Appendix 1 for 
questionnaire) and laboratory confirmation of COVID-19 infection.   
8.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
1. Need for hospitalization 
• This is defined by documentation in the case report form (CRF) of physician 
referral to hospital for admission 
2. Hospital length of stay 
• The number of overnight stays in the hospital, entered into the CRF 
3. ICU admission 
• Documentation in the CRF of physician recommendation for ICU transfer.  
4. ICU length of stay 
• The number of overnight stays in the ICU 
5. Mechanical ventilation 
• Documentation in the CRF of administration of mechanical respiratory assistance 
and length of time such assistance required 
6. Duraton of mechanical ventilation 
• Documented in the CRF by physician 
7. Recovery time from COVID-19  
• Defined as testing negative, plus the time for full recovery as determined by 
physician 
• Documented in the CRF by physician 
8. Change in any existing comorbidities (e.g., worsening congestive heart failure) or newly 
diagnosed disease 
• Documented in the CRF by physician 
9. Incidence of secondary non-COVID-19 infections (relapses, superinfections and new 
infections).  
• Documented in the CRF by physician 
10. Change in T lymphocyte subsets (CD4, CD8) 
• Samples taken at enrollment, at 8 weeks and at 6 months, or at time of hospital 
admission if that is required 
11. Mortality 
• COVID-19 related, or non-COVID-19 related; documented in the CRF by 
physician. 
8.3 
Safety Endpoints 
The safety endpoints include adverse events (AEs), vital signs and laboratory parameters. 

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9 
STUDY POPULATION 
9.1 
Sample Size 
A total of up to 240 patients will be enrolled. Dr. Musio (Co-Investigator) is a member of 
Nephrology Associates of Northern Virginia. This group manages over 700 hemodialysis 
patients at several sites in or near Fairfax Va. Three of these sites will participate in this research 
project. Members of the Neprhology Associates of Northern Virginia have reviewed the 
proposed research and have endorsed participation.  
9.2 
Inclusion Criteria  
1. Age 60 years or greater 
2. Signed informed consent 
3. Patients with ESRD, receiving hemodialysis 2 or more times each week and expected to 
continue on dialysis indefinitely. 
9.3 
Exclusion Criteria 
1. Patients on short-term hemodialysis, such as those with transient renal dysfunction 
associated with acute illness who are projected to have return in renal function 
2. Patients for whom renal transplantation is anticipated within the next six months 
3. Patients with an anticipated survival of less than 3 months 
4. Patients with symptoms that might be attributable to COVID-19 infection (see Appendix 
1 for symptom questionnaire) 
5. Patients who test positive for SARS-CoV2 
6. Patients with active infectious disease requiring antibiotics  
7. Patients with hospitalization within the previous 3 months for acute myocardial infarction 
or congestive heart failure 
8. Patients with advanced malignancy receiving cytotoxic chemotherapy 
9. Patients with a Karnofsky Performance Scale score of less than 60 
10. Patientswith prior history of solid organ (kidney, liver, heart, lung, pancreas) or bone 
marrow transplant 
11. Patients with active autoimmune disease on immunosuppressive medication 
12. Patients receiving Plaquenil 
13. Patients who have participated in an investigational drug or device trial in the previous 30 
days 
14. Patients with a history of allergy or intolerance to Ta1 
15. Patients with any other medical or psychiatric condition that, in the opinion of the 
Investigator, would compromise patient safety or interfere with the objectives of the 
protocol or completion of the protocol treatment. 
9.4 
Removal of Subjects  
In accordance with the Declaration of Helsinki, subjects have the right to withdraw from the 
study at any time for any reason. The Investigators (used throughout this protocol to refer to 
primary investigator or co-investigator) also have the right to withdraw subjects from the study. 
Subjects may be removed from the study for the following reasons: 

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• Adverse events (AEs) 
• At the request of the Investigator  
• Subject is unwilling or unable to comply with study protocol (noncompliance) 
• Termination of the study. 
If the reason for removal of a subject from the study is an AE, the specific event and any related 
test results will be recorded on the CRF. The subject will be followed until the AE resolves, 
becomes chronic, or the subject is lost to follow up. If a subject dies, the date of the last dose of 
clinical trial material (CTM) and all observations collected up to the time of study termination 
will be recorded on the CRF as will be the reason for death.  
If a subject or the Investigator chooses to discontinue CTM, the Investigator will inquire whether 
the subject will agree to participate in remaining study evaluations. 
If a subject is removed from the study at the request of the Investigator, the date of the last dose 
of CTM and all observations collected up to the time of termination will be recorded on the CRF 
along with the reason for termination, and scheduled safety evaluations and follow-up 
examinations will be conducted, if possible.  
The date that a subject discontinues and the reason for discontinuation will be recorded in the 
CRF. Subjects who discontinue after randomization will not be replaced. If a subject withdraws 
consent from the study during treatment, follow-up visit study procedures should be conducted, 
as possible. 
 
10 STUDY TREATMENT 
10.1 Treatment Plan 
For those in the treatment arm, Ta1 at a dose of 1.6 mg will be administered SC in 1 mL of 
diluent upon completion of dialysis treatment twice weekly (separated by at least 2 full days 
without Ta1 injection) after dialysis for a total of 8 weeks.  Control patients will not receive 
injection injections. 
Subjects who report respiratory illness symptoms (see Appendix 1 for symptom questionnaire) at 
the designated inventory times (Table 1) or in the interval between those designated times will be 
tested for COVID-19 virus.  If the COVID-19 assay is positive, this will complete the treatment 
phase of the research protocol for that individual. However, the subject will remain on study with 
continuation of the designated assessments to assess severity of disease (e.g., need for 
hospitalization, ICU management, mechanical ventilation, mortality). 
10.2 Identity of Clinical Trial Material 
Ta1 clinical trial material (CTM) will be generously provided for this study by SciClone, Inc 
(China). Ta1 is contained, stored, and dispensed from individual tamper-proof glass vials with 
1.6 mg Ta1 as a lyophilized cake containing 5% mannitol, buffered with phosphate to pH 6.4 -
7.3. Vials are reconstituted with 1 mL of supplied diluent (sterile Water for Injection), prior to 
subcutaneous (SC) administration. 

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10.3 Labeling and Packaging 
ZADAXIN lyophilisate for solution for injection is a sterile, white to off-white lyophilized 
powder, containing Ta1 manufactured by solid-phase peptide synthesis.  
The CTM intended for investigational use will be stored in a locked area with limited access, 
refrigerated between 2°C and 8°C. 
10.4 Study Drug Accountability 
The Investigator or designed site personnel are responsible for ensuring adequate accountability 
of all used and unused CTM. This includes acknowledgement of receipt of each shipment of 
CTM (quantity and condition), and documentation of dispensing, returns, and destruction of 
CTM. Dispensing records will document quantities of CTM received. Quantities dispensed will 
be documented, including date dispensed, subject identification number, and the initials of the 
person dispensing the CTM. Study drug accountability records must be readily available for 
inspection by regulatory authorities at any time. 
The Investigator will not allow CTM to be given to any subject not enrolled into the treatment 
arm of the study or any unauthorized person. 
10.5 Method of Assigning Subjects to Treatment  
Subjects who meet all inclusion and exclusion criteria will be centrally randomized 1:1 to receive 
either no treatment or 1.6 mg Ta1 in 1 mL doses to be delivered twice weekly after dialysis (with 
treatment days separated by at least 2 full days without Ta1 injection), via SC injection for 8 
weeks, in accordance with a computer-generated randomization schedule prepared by the Inova 
Biostatistical core.  
Randomization will be stratified by dialysis site. 
10.6 Selection of Doses 
For those randomized to the treatment arm, Ta1 will be administered SC at doses of 1.6 mg twice 
weekly after dialysis for 8 weeks, similar to the dose and regimen used in many previous clinical 
trials and in commercial use in China.  
This dose is supported by safety studies which show that Ta1 is well tolerated; in particular, no 
safety signals were seen in studies which enrolled subjects with: acute respiratory disease due to 
cytomegalovirus (CMV) or pneumonia, chronic obstructive pulmonary disease, severe lung 
infections, ESRD requiring hemodialysis, chronic infections (hepatitis B, hepatitis C, 
HIV/AIDS), cancer and those being treated with chemotherapy, or elderly subjects. 
Pharmacokinetic studies show that there is no accumulation of Ta1 and the T1/2 is 2 hours.  
The proposal to evaluate a single dose rather than dose escalation is based on previous studies 
which have shown that doses above 1.6 mg showed show little, if any, improvement in response, 
and the mechanism of action of Ta1 (immune modulation rather than directly targeted therapy) 
suggests that the optimal dose should be equivalent no matter which indication is being 
investigated. 

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Support for the safety of the proposed dosing regimen is also seen in the nonclinical safety 
studies, which showed no adverse effects in rodents (mice and rats) at doses up to 20 mg/kg/day 
for acute dosing or 6 mg/kg/day for 6 months with repeat dosing; and no adverse effects were 
seen in marmosets dosed at 1 mg/kg/day for 6 months of repeat dosing. Conservatively, the 
marmoset no adverse effect level (NOEL) of 1 mg/kg/day represents a 50–fold safety margin 
over dosing of 1.6 mg.  
10.7 Concomitant Therapy 
Any concomitant therapy used from the time a subject signs an ICF through the 6-month end of 
study visit will be recorded on the CRF. In addition, for any serious adverse events (SAEs) that 
require medication for treatment, those medications will be recorded on the concomitant 
medications page. The medication name, dose, route of administration, start and stop dates and 
indication for use will be recorded.  
There are no prohibited medications for this study protocol. 
10.8 Standard of Care 
The Investigator will follow routine standard of care for elderly renal dialysis patients.  
The Investigator or any physician member of the Nephrology Associats of Northern Virginia 
may prescribe any concomitant medication or supportive therapy deemed necessary to provide 
adequate standard of care. 
Subjects who have been determined to have received investigational products (exclusion criteria 
#6) either 30 days prior to their initiation of the study, or during the course of the study, will not 
be removed from the study; however, this fact will be recorded. 
11 ASSESSMENTS 
11.1 Efficacy Assessments 
Clinical and laboratory evaluations of each participating subject will occur at two-week intervals. 
This will include initial medical history and physical examination (Investigator), a brief 
interview, symptom inventory and examination (vital sign, physical exam; see Appendix 1 for 
symptom questionnaire) twice weekly during the study period (research nurse), and serial 
laboratory evaluations obtained every 2 weeks during the treatment phase and then monthly for a 
total of 6 months.  
All clinical and laboratory data will be entered on the subject’s CRF with data entered at times 
indicated in Table 1 and secured in a cloud-based secure archive. The clinical data will include a 
symptom inventory, change in medical status (infection or non-infection), hospitalizations, 
intensive care unit admission, requirement for mechanical ventilation (respirator or 
extracorporeal membrane oxygenation [ECMO]), length of stay in the hospital and in the ICU, 
and survival. If subjects report respiratory symptoms (see Appendix 1 for symptom 
questionnaire), they will be tested for SARS-CoV2 and influenza. If these tests are negative, a 
full respiratory viral infection panel will be run. 

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In addition to screening for SARS-CoV2, routine complete blood count (CBC), and standard 
chemistry evaluations, additional markers of infection including procalcitonin, C-reactive protein 
(CRP), and lactate dehydrogenase (LDH) will be followed. Further, T lymphocyte subsets CD4 
and CD8 will be determined by flow cytometry at enrollment, at eight weeks and upon 
completion of the six-month project. 
Aliquots of serum will be cryopreserved for all subjects to assess COVID-19 antibody 
throughout the course of this study once the methodologies have been worked out and the assays 
are commercially available. It is anticipated that these serum samples will all be run upon 
completion of the trial. 
Subjects who report respiratory illness symptoms (see Appendix 1 for symptom questionnaire) at 
the designated inventory times (Table 1) or in the interval between those designated times will be 
tested for COVID-19 virus. If the COVID-19 assay is positive, this will complete the treatment 
phase of the research protocol for that individual. However, the subject will remain on study with 
continuation of the designated assessments to assess severity of disease (e.g., need for 
hospitalization, ICU management, mechanical ventilation, mortality). 
In addition to infection with COVID-19, the following assessments will be collected and 
recorded at intervals in Table 1:  
• Need for hospitalization  
• Hospital length of stay 
• ICU admission  
• ICU length of stay 
• Mechanical ventilation 
• Mortality 
• Incidence of secondary infections 
• CD4, CD8, CD4/CD8. 
Assessment for secondary infections will be documented in the CRF. Sites will be required to 
record all infections occurring from the time of enrollment until completion of the study 6 
months after enrollment.  Data will include the site of the infection, the evidence of infection, the 
organism cultured, and the antimicrobial susceptibility data.  
The study will use the Inova Central Laboratory for conducting all laboratory investigations 
included in this study. 
11.2 Safety Assessments 
Safety will be assessed by collecting, recording AEs and reviewing all adverse events in a timely 
fashion.  The investigators, study nurse and clinical trials specialist will meet weekly (Safety 
Meeting) for this purpose, or as needed if a serious adverse event is recognized that requires 
immediate attention.   
Each enrolled subject will be briefly examined at two week intervals. Included in that exam will 
be vital signs, examination of the head, eyes, ears nose and throat and auscultation of the chest. 

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Routine clinical labs which include complete blood count with white blood cell differential and 
comprehensive metabolic panel (sodium, potassium, chloride, carbon dioxide, glucose, blood 
urea nitrogen, creatinine calcium, total protein, albumin, total protein, aspartate amino 
transaminase, alanine amino transaminase) will be reviewed for each research subject at two 
week intervals.  These data will be reviewed at the weekly Safety Meeting. 
The Investigator will assess all abnormal clinical laboratory results for clinical significance in a 
timely fashion. A notation of clinically significant or not clinically significant, with initials and 
date, will be documented on the respective laboratory report next to any abnormal value. An 
abnormal laboratory value of clinical significance will be considered and documented as an AE 
if, in the opinion of the Investigator, it is clinically significant and not considered part of the 
underlying clinical condition. 
Investigators will classify adverse events and laboratory findings as mild, moderate, or severe 
based on the perceived clinical significance of the event and laboratory finding in the patient. 
The Investigator will follow proper AE and SAE reporting procedures. 
12 STUDY PROCEDURES 
12.1 Schedule of Events 
A schedule of study procedures is outlined in Table 1. 
12.2 Screening  
Once FDA and IRB approval are obtained, the research team will promptly initiate the process of 
subject recruitment.  Recruitment of all subjects will be completed in four months and the 
observation phase in one year.  Posters and leaflets will be prepared for distribution at the study 
sites.  Interested individuals will be directed by site personnel to discuss the study with any of 
our research staff and informed consent will be obtained by the Investigator or research nurse. 
The following screening observations and procedures will be completed prior to randomization: 
• Obtain a signed Health Insurance Portability and Accountability Act (HIPAA) 
authorization 
• Assess a subject against the inclusion/exclusion criteria 
• Obtain a signed IRB-approved informed consent (ICF) 
• Perform physical exam and obtain medical history 
• Assess performance status (Karnofsky Performance Scale) 
• Take a nasopharyngeal swab to test for SARS-CoV2 
• Draw blood sample for: 
o Complete blood count (CBC) and standard chemistry surveys 
o Nonspecific markers of infection (procalcitonin, CRP, and LDH) 
o CD4, CD8 (flow cytometry) 
o Serum cryopreservation for future serologic assay once it is available. 
12.3 Weekly Study Procedures (for 8 weeks) 
The following observations and procedures will be conducted: 

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• Record abbreviated physical exam, height, weight, viral signs 
• Record respiratory virus symptoms (see Appendix 1 for questionnaire) 
• Record comorbidity signs and symptoms 
• Record any concomitant medications 
• Record AEs and SAEs  
• Record secondary infections 
• Administer dose of Ta1 (or no treatment) after dialysis (twice per week, with at least 
two full days between treatments). 
12.4 Every Other Week Study Procedures (for 8 weeks) 
The following observations and procedures will be conducted: 
• Record any concomitant medications 
• Record AEs and SAEs  
• Record secondary infections 
• Draw blood sample for serology 
o Routine complete blood count (CBC) and standard chemistry surveys 
o Serum cryopreservation for future serologic assay once it is available.  
12.5 Additional Blood Draws at Week 4, Week 8 
• Draw blood sample for serology 
o Nonspecific markers of infection (procalcitonin, CRP, LDH) 
o CD4, CD8 (flow cytometry). 
12.6 Additional Procedures if respiratory infection symptoms are seen 
• Take nasopharyngeal swabs for analysis 
o SARS-CoV2 and influenza assay 
o If SARS-CoV2 and influenza assay are negative: full respiratory virus panel.  
12.7 Monthly Follow-up Visits (for 4 months) 
The following observations and procedures will be conducted: 
• Record vital signs, including temperature, systolic and diastolic blood pressures, heart 
rate, and respiration rate 
• Record respiratory virus symptoms (see Appendix 1 for questionnaire) 
• Record any concomitant medications 
• Record AEs and SAEs  
• Record secondary infections 
• Draw blood sample for serology  
o Routine complete blood count (CBC) and standard chemistry surveys 
o CD4, CD8 (flow cytometry) 
o Serum cryopreservation for future serologic assay once it is available. 

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13 ADVERSE EVENT REPORTING 
Throughout the study, AEs will be recorded onto the CRF regardless of whether or not the AEs 
are considered study treatment-related. All AEs with onset dates after the date the subject signed 
the ICF through the second week 8 visit will be recorded as an AE on the CRF. Conditions 
existing prior to signing the ICF will be recorded as part of the subject’s medical history. All 
SAEs with onset dates after the subject signs the ICF through the second week 8 visit must be 
recorded following the guidelines in Sections 13.4 and 13.8.  To avoid confusion, AEs will be 
recorded in standard medical terminology.  
The Investigator is responsible for assessing the relationship of AEs to CTM (see Section 13.3). 
13.1 Adverse Event Definition 
An adverse event is any untoward medical occurrence in a subject administered an 
investigational product and which does not necessarily have a causal relationship with this 
treatment. An AE can be any unfavorable and unintended sign (for example, an abnormal 
laboratory finding), symptom or disease temporally associated with the use of an investigational 
product, whether or not considered related to this investigational product. This includes an event 
that emerges during treatment having been absent pre-treatment or an event that worsens relative 
to the pretreatment state. Recurrent symptoms of a chronic preexisting condition are not 
considered AEs, unless they occur in a worse or unexpected pattern during CTM administration.  
13.2 Assessing Severity of Adverse Events 
The severity of AEs will be designated by the investigator as mild (Grade 1), moderate 
(Grade 2), severe (Grade 3), life-threatening (Grade 4), or fatal (Grade 5),  
Adverse Event Severity 
Grade 
Definition 
Mild –  
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
Moderate – 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)1 
Severe –  
Grade 3 
Severe or medically significant, but not immediately life threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL2 
Life-threatening – 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Death –  
Grade 5 
Death related to AE 
1Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
2Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not being 
bedridden. 

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13.3 Assessing Relationship of Adverse Event to Study Treatment 
All AEs will be categorized by the Investigator with respect to their possible relationship to 
study treatment. The relationship between study treatment and the AE may be considered related 
or not related. The criteria for each category are listed below: 
• Related: When there is a reasonable possibility that the study treatment caused the 
reported AE 
• Not related: When there is no reasonable possibility that the study treatment caused 
the reported AE. 
13.4 Recording of Adverse Events 
All AEs with onset dates after the subject signed the ICF through the 6-month visit will be 
recorded on the CRF. All AEs must be recorded on the appropriate CRF, regardless of their 
severity or relationship to the CTM.  All AEs that meet the seriousness criteria (Section 13.6) 
will be recorded as an SAE.  
All clinical events are to be recorded, including both observed (such as any reaction at injection 
sites) and volunteered problems, complaints, or symptoms. The need to capture this information 
does not depend upon the clinical event’s association with the use of the CTM. Adverse events 
resulting from concurrent illnesses, reactions to concurrent medications, or clinically significant 
progression of disease states are also to be recorded. 
13.5 Adverse Event Recording Period 
AEs will be collected and recorded on the CRF from the time the ICF is signed by the subject 
through the 6-month follow-up visit.  
13.6 Serious Adverse Event Definition 
A serious adverse event (SAE) is defined as any AE occurring at any dose regardless of 
relationship to CTM that results in any of the following outcomes: 
• Death 
• Is life-threatening  
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Other significant medical events. 
In addition, all AEs assessed by the investigator with severity of Grade 4 or Grade 5 should be 
reported as SAEs. An important medical event that may not result in death, be life-threatening or 
require hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, it may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed above. 
Complications that occur during hospitalization are AEs. If a complication prolongs a 
hospitalization, it is an SAE. 

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As used in this study, the term inpatient hospitalization is defined as formal admission to a 
hospital for medical reasons or evaluation in the Emergency Department of a hospital even if not 
admitted. 
When an SAE occurs in a subject receiving a product as a concomitant medication, the SAE 
must be processed and reported. 
13.7 Serious Adverse Event Recording Period 
The Investigator will collect and record SAEs from the time the subject signs the ICF through the 
6-month follow-up visit.  
13.8 Regulatory Reporting of Adverse Events 
The Investigator will determine whether the SAE must be reported to the FDA within 7 or 
15 days, and if so, will report the event to the FDA. The Investigator will report all SAEs to their 
IRB, as required. Adverse events will be reported to regulatory authorities in compliance with 
local and regional law and established guidance. The format of the reports will be dictated by 
local and regional requirements.  
13.9 Data Safety Monitoring Board (DSMB) 
Acknowledging the inherent vulnerability of our study population (older hemodialysis patients), 
a DSMB will be established with a mission to ensure that the interests of the patients entered in 
the trial are being well served (i.e., the risk-benefit ratio is appropriate) and that the scientific 
integrity of the trial is maintained from trial initiation to completion [21]. The DSMB will be 
comprised of three independent physicians with expertise in nephrology, geriatric medicine and 
infectious disease as well as one independent biostatistican. The committee will meet at trial 
initiation and quarterly for the one-year duration of the study. 
The study will be stopped if the DSMB believes that the number or severity of treatment-related 
adverse events suggests that it is in the best interests of the patients to do so. 
14 DATA MANAGEMENT 
Data will be entered onto the CRFs. The Investigator should ensure the accuracy, completeness 
and timeliness of the data recorded on the CRFs. 
15 STATISTICAL ANALYSIS 
15.1 Sample size justification 
It has been speculated that infection rates may be as high as 40% in the general population and 
for those over the age of 60 years, particularly those with underlying comorbidities, the rate may 
be higher. Further, patients who receive dialysis two or three times weekly at dialysis centers are 
more likely to be exposed to virus than the general elderly population. In as much as there are no 
existing data demonstrating the effects of Ta1 in prevention of COVID-19 infection, in this pilot 
project we have elected to sample 240 subjects, anticipating that 40 subjects will drop off study 
for any of a number of reasons. That will leave ~200 enrolled subjects with complete data 
availability. We justify the choice of sample size below. 

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Each sample size calculation depends on the type of endpoints, the variability of data, analysis 
methods used, and the minimal difference (or effect size) that we wish to be able to detect 
between the treatment (with Zadaxin) or control (without Zadaxin) groups. There are four types 
of endpoints for this study, dichotomous (e.g., infection of COVID19, the primary endpoint; ICU 
admission; or mortality), polytomous (e.g., health changes: no change, moderate, severe 
changes), counts (e.g., occurrence of non-COVID-19 infections), or continuous outcome 
variables (e.g., CD4, CD8, CD4/CD8, length of hospital stay, recovery time from COVID19). 
For a dichotomous outcome, a suitable model is a logistic regression with the treatment status 
(treated or not treated with Zadaxin) as the primary covariate, demographic information (age, 
gender, race), health/medical information (e.g., Karnofsky score, co-morbidity, and other 
biomarkers) and environmental information (treatment center, among others) as other relevant 
covariates. Assume the infection rate for the control group is about 0.40 and with a significance 
level of 0.05 (unless specified otherwise), if we use a simple logistic regression, a sample of size 
200 will be able to detect a change at least at 0.185 in the infection rates between the treatment 
and control groups with a power of 80%. If we have a bigger sample size, say 234, we would be 
able to detect a change with a minimal difference of 0.17 with the same power or a minimum 
difference of 0.185 with a power of 86.5%. Using more comprehensive procedures (below) or if 
the actual difference is (much) larger than the minimal difference, we will have a (much) higher 
power than 80%  to detect the actual difference. If we make a conservative adjustment for 
multiple comparisons incorporating other covariates after a pre-screening step, at an adjusted 
significance level 0.005, a sample of size 205 will provide 80% power for detecting a change of 
at least as large as 0.23. Using a multiple logistic regression model that takes into account the 
correlation among the various covariates, say if the correlation is 0.2, we can detect a minimal 
difference at 0.202 with a sample size of 200. If the correlation is 0.5, the minimum detectable 
difference would be 0.25. The highly correlated covariates that lead to multicollinearity will 
indicate the need for removal of redundant covariates in modeling the endpoint, and the removal 
will lead to more degrees of freedom in our study and the same power in detecting the even 
smaller difference. We will use all the sample we have and incorporate censored data or treat 
missing information with survival or a more comprehensive model than the logistic regression; 
thus, we expect to be able to detect a smaller minimal difference or have a much higher power to 
detect the actual difference in the infection rates than given above.  
For a continuous endpoint, with a sample size of 201, using the simplest testing procedure (with 
a possible transformation of the endpoint variable), we will be able to detect an effect size at 
least at 0.35 between the treatment and control groups with a power of 80%. Since we will use a 
general linear model to delineate the effects or variations due to covariates/factors, we expect to 
be able to detect a smaller minimal effect size or a higher power to detect the actual difference 
that is bigger than the minimal effect size. In a very conservative sense, comparing a polytomous 
response between treatment and control can be viewed as a multiple testing problem of 
comparing proportions for each of the categories. For response variables with three categories, if 
the proportion of a certain category is approximately 0.3, a sample of size 202 will enable us to 
detect a minimal change of 0.19 with a power of 80%. We emphasize that this calculation is very 
conservative, and we expect have much better performance, both in terms of detection of smaller 
departure and having better power. For the ordinal polytomus outcome, we are interested in 

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identifying if the treatment improves the proportion of different categories of the outcome than 
that of control. Assume that the response has 3 categories with equal proportion in the overall 
population (averaged over control and treatment). With a sample size of 200 we can detect a 
minimal improvement of size 0.725 in the overall odds ratio with 80% power. The count 
variables can be modeled as continuous with appropriate transformation and the sample size 
justification will be similar to that of a continuous response.  
15.2 Data analysis plan 
The primary goal of the analysis is to study the effect of the treatment on the outcome variables, 
in consideration of other covariates, including the demographic information and medical history 
of the participants and dialysis centers, which can potentially interact with the treatment. First, 
we will do an exploratory analysis of all the covariates altogether and stratified in the treatment 
and control group. We will study the effect of each of these covariates separately and together on 
the outcome. In the comprehensive study of all factors, we will build several models, including 
both parametric and tree-based models. We will also consider relevant interaction between the 
independent variables in the model. For the parametric models, we will use logistic regression 
for the binary outcomes, general linear regression (after a possible transformation of some 
covariates) for the continuous outcomes, Poisson regression with an over-dispersion test or a 
general log-linear model, for count outcomes, and a multinomial regression for the categorical 
variables with more than two categories. We will assess the fitted models based on model 
diagnostics and goodness-of-fit/prediction measures, such as adjusted R2, AIC, BIC, and cross-
validation. A follow-up analysis will be done based on the results obtained from the various 
regression models. All the significant first-order and interaction effects will be further analyzed 
to understand the nature of the effect, and possibly considering further models stratified by 
relevant covariates. 
Interim analyses will be done at least in the interval of 1, 3, and 6 months for the purpose of 
monitoring, presentations to the monitoring board,  and any remedies (as needed) to ensure the 
quality of the study and safeguard the study population. 
16 ETHICS 
16.1 Good Clinical Practice 
The Investigator will ensure that this study is conducted in full compliance with the principles of 
the Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and South 
Africa), ICH guidelines, in particular ICH GCP E6, and with the laws and regulations of the 
United States. Because this study is conducted under a U.S. IND, the Investigator will ensure 
adherence to the basic principles of Good Clinical Practice, as outlined, for example, in 21 CFR 
§312.50 and 312.56. 
16.2 Institutional Review Board 
The protocol and ICF for this study must be reviewed and approved by an appropriate IRB 
before subjects are randomized into the study. It is the responsibility of the Investigator to assure 
that all aspects of the institutional review are conducted in accordance with the requirements of 
all regulatory authorities.  

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16.3 Subject Information and Informed Consent 
In accordance with regulatory and local ethics committee requirements, before study procedures 
are performed, subjects will be informed about the study and required to sign the IRB-approved 
ICF along with authorization to collect protected health information under HIPAA. This form 
will be signed after adequate explanation of the aims, methods, objective and potential hazards of 
the study and prior to undertaking any study-related procedures. Informed consent will be 
obtained according to the applicable IRB requirements. No subject is to be screened or treated 
until an ICF has been obtained. The signed ICF will be retained with the study records. Each 
subject will also be given a copy of his or her signed ICF at the screening visit.  
16.4 Financial Disclosure by Investigators  
Since this is a “covered” clinical trial, the Investigator will ensure that 21 CFR §54 is adhered to. 
A “covered” clinical trial is any study of a study drug or device in humans submitted in a 
marketing application or reclassification petition subject to this part that the applicant or the FDA 
relies on to establish that the product is effective (including studies that show equivalence to an 
effective product) or that make a significant contribution to the demonstration of safety. This 
requires that Investigators (inclusive of family members) provide documentation of their 
financial interest or proprietary interests in the study drug being studied. This documentation 
must be provided prior to the participation of the Investigator.  
16.5 Archiving and Data Retention 
According to 21 CFR §312.57, an Investigator shall retain adequate records for the study 
including copies of each subject’s CRFs, medical records, laboratory reports, ICFs, study drug 
accountability records, safety reports, information regarding subjects who were withdrawn and 
any other pertinent data. All records are to be retained by the Investigator for a period of 2 years 
following the date a marketing application is approved for the study drug for the indication for 
which it is being investigated or if no application is to be filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and the FDA is 
notified. The records will be available for copying and inspection if requested by regulatory 
authorities.  
If the responsible Investigator retires, relocates or for other reasons withdraws from the 
responsibility of keeping records, custody must be transferred to a person who will accept the 
responsibility.  
16.6 Confidentiality 
The Investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties.  
The Investigator must keep a screening log showing names and addresses for all screened 
subjects and all subjects randomized into the trial. 
 

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17 REFERENCES 
1. 
Shen, S.Y., et al., eds. Age-dependent enhancement of influenza vaccine response by 
thymosin in chronic hemodialysis patients. Biomedical Advances in Aging ‘88, ed. A.L. 
Goldstein. 1990, Plenum Medical Publishers. 523-530. 
2. 
Zhou, P., et al., A pneumonia outbreak associated with a new coronavirus of probable bat 
origin. Nature, 2020. 579(7798): p. 270-273. 
3. 
Sun, P., et al., Understanding of COVID-19 based on current evidence. J Med Virol, 2020. 
4. 
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278-280. 
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Huang, C., et al., Clinical features of patients infected with 2019 novel coronavirus in 
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Tang, B., et al., Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for 
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375-84. 
11. Gravenstein, S., et al., Augmentation of influenza antibody response in elderly men by 
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18. Naylor, P.H. and M.G. Mutchnick, Immunotherapy for hepatitis B in the direct acting 
antiviral era: Reevaluating the thymosin alpha1 efficacy trials in the light of a combination 
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19. Costantini, C., et al., A Reappraisal of Thymosin Alpha1 in Cancer Therapy. Front Oncol, 
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Soc Nephrol, 2017. 12(5): p. 854-863. 
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Table 1: Study Schedule 
 
PROCEDURE 
 
1SCREEN 
 
STUDY ACTIVITIES 
 
W1 
W2 
W3 
W4 
W5 
W6 
W7 
W8 
M3 
M4 
M5 
M6 
Informed Consent 
● 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria Reviewed 
● 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
● 
 
 
 
 
 
 
 
 
 
 
 
 
2Physical examination 
● 
 
 
 
 
 
 
 
 
 
 
 
● 
Abbreviated PE, height, 
weight, vital signs 
 
! 
! 
! 
! 
! 
! 
! 
! 
! 
! 
! 
! 
4Respiratory virus 
symptom inventory (see 
Appendix 1) 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
SARS-CoV2 assay 
● 
 
● 
 
● 
 
● 
 
● 
● 
● 
● 
● 
3Clinical and research 
blood draws  
● 
 
● 
 
● 
 
● 
 
● 
● 
● 
● 
● 
Lymphocyte Subsets 
(CD4, CD8); markers of 
infection (procalcitonin, 
CRP, LDH) 
● 
 
 
 
● 
 
 
 
● 
 
 
 
 
Secondary infections  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
5Comorbidity inventory 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
6 SARS-CoV2 and 
influenza assays; if 
negative: respiratory 
virus panel  
 
-- conducted if signs of infection are seen -- 
 
 
 
 
Record AEs, SAEs 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record Concomitant 
Therapies/Procedures 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
6Ta1 administration 
 
®  ® 
®  ® 
®  ® 
®  ® 
®  ® 
®  ® 
®  ® 
®  ® 
 
 
 
 
Subject Compensation  
 
 
● 
 
● 
 
● 
 
● 
 
● 
 
● 
1Screening and enrollment to be completed no more than 14 days prior to initiation of study. 
2Full physical exam to be performed either at screening or on Day 1 and again at completion of study. 
3Clinical and research labs – please refer to the Study Procedures section (Serum will be cryopreserved until completion of study and 
assays run once serologic assay is available for COVID-19) 
4Respiratory virus symptom inventory to include the description of cough, fever, shortness of breath, malaise, sore throat occurring 
over the prior week. If any are present, the information will be brought to the attention of PI or CoI. 
5Signs and symptoms correlating with pre-existing or newly developed comorbidities will be inventoried. 
6Ta1 will be administered twice weekly on dialysis days immediately upon completion of dialysis, with at least two full days between 
treatments. 
 
 
 

 
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Page 32 of 32 
 
 
 
 
18 APPENDIX 1 
Respiratory Symptom Inventory 
 
Symptom 
Screen W1 W2 W3 W4 W5 W6 W7 W8 M3 M4 M5 M6 
Cough 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever >100.4 
 
 
 
 
 
 
 
 
 
 
 
 
 
Shortness of 
breath 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sore throat 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gastrointestinal 
symptoms 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malaise 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
 
 
 
 
 
 
 
 
 
 
 
 
 
Muscle pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
Loss of taste 
and/or smell 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
(describe)