Conditions: Coronavirus Disease 2019
Keywords: SARS-CoV-2 Cytokines Spleen Tyrosine Kinase ARDS
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 59
Healthy volunteers: no

Brief summary:
Background:

COVID-19 is a new disease caused by SARS-CoV-2 that was identified in 2019. Some people who get sick with COVID-19 become ill requiring hospitalization. There are some medicines that may help with recovery. Researchers want to see if a drug called fostamatinib may help people who are hospitalized with COVID-19.

Objective:

To learn if fostamatinib is safe in patients who are hospitalized with COVID-19 and gain earlier insight into whether it improves outcomes.

Eligibility:

Adults age 18 and older who are hospitalized with COVID-19.

Design:

Participants will be screened with a physical exam, including vital signs and weight. They will have a blood test and chest x-ray. They will have a COVID-19 test as a swab of either the back of the throat or the back of the nose. They will take a pregnancy test if needed.

Participants will be randomly assigned, to take either fostamatinib pills or a placebo twice daily for up to 14 days in addition to standard of care for COVID-19. If they can swallow, they will take the pills by mouth with water. If they cannot swallow or are on mechanical ventilation, the pills will be crushed, mixed with water, and given through a tube placed through the nostril, or placed in the mouth, down the esophagus, and into the stomach. Blood samples will be taken daily. Participants will return to the Clinical Center for safety follow-up visits. At these visits, they will have a physical exam and blood tests. If they cannot visit the Clinical Center, they will be contacted by phone or have a telehealth visit.

Participation will last for about two months

Detailed description:
Coronavirus Disease 2019 (COVID-19) is the disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS) in a subset of patients with a known high mortality rate. Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock along with endothelial dysfunction and subsequently micro and macrovascular thrombosis.

Much of the underlying pathology of SARS-CoV-2 is thought to be secondary to a dysregulated immune response and more recently a hypercoagulable state leading to immunothrombosis. Currently, two therapies have shown efficacy in large multicenter trials for the treatment of COVID-19, one of which is an antiviral (remdesivir) and the other is an immunosuppressant corticosteroid meant to dampen the immune response (dexamethasone).

Spleen tyrosine kinase (SYK) is a cytoplasmic tyrosine kinase involved in the intracellular signaling pathways of many different immune cells. In this pilot study we propose to use fostamatinib (an SYK inhibitor) as a targeted therapy for the immunological complications of hospitalized patients with COVID-19. The biological mechanisms by which SYK inhibition may improve outcomes in patients with COVID-19 include the inhibition of pro-inflammatory cytokines by monocytes and macrophages, decreased production of neutrophil extracellular traps (NETs) by neutrophils, and inhibition of platelet aggregation; three pathways that are mediated through Fc receptors (FcR) recognition of antigen-antibody complexes or activation of c-type lectin receptors (CLEC).

This is a randomized, double-blind, placebo-controlled trial of fostamatinib for the treatment of hospitalized patients with COVID-19.

We will randomly assign fostamatinib or matched placebo (1:1) to 60 eligible COVID-19 patients who are a 5 to 7 on the 8-point scale (requiring supplemental oxygen via nasal canula or noninvasive ventilation, requiring mechanical ventilation or extracorporeal membrane oxygenation).

Arms:
arm 1: fostamatinib in combination with standard of care (SOC) for the treatment of COVID-19 arm 2: Placebo in combination with standard of care (SOC) for the treatment of COVID-19

Interventions: intervention 1: Placebo intervention 2: fostamatinib
Intervention descriptions: intervention 1: Placebo tablets to match fostamatinib 100 mg and 150 mg will be provided. intervention 2: The study intervention is fostamatinib, an inhibitor of spleen tyrosine kinase that will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses. Subjects will receive standard of care and be randomized to receive fostamatinib or matching placebo.

Protocol document:
Prot_SAP_001.pdf: 
Abbreviated Title: Fostamatinib for COVID 
Version Date: 09/17/2020 
 
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Abbreviated Title: Fostamatinib for COVID 
Protocol #: 000110 
IND #: 152131 
Version Date: 09/17/2020 
 
Title: A Phase II Study Evaluating Fostamatinib for Hospitalized Adults with COVID-19 
 
 
NIH Principal Investigator: 
Jeffrey R. Strich, MD, MHS 
Clinical Center, Critical Care Medicine Department 
Building 10, Rm 2C-145 
9000 Rockville Pike 
Bethesda, MD 20892 
Phone: 301-496-9320 
E-mail: jeffrey.strich@nih.gov 
 
Investigational Agent: 
Drug Name: 
Fostamatinib 
IND Number: 
152131 
Sponsor: 
NHLBI OCD 
Manufacturer: 
Rigel Pharmaceuticals  
 
Coordinating Center: National Heart, Lung, and Blood Institute, Office of the Clinical Director 
Responsible Data Safety Monitoring Board (DSMB): NHLBI Lung DSMB 
 
 


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TABLE OF CONTENTS  
TABLE OF CONTENTS ................................................................................................................ 2 
STATEMENT OF COMPLIANCE ................................................................................................ 6 
1 
PROTOCOL SUMMARY ...................................................................................................... 7 
1.1 
Synopsis ........................................................................................................................... 7 
1.2 
Schema ............................................................................................................................. 9 
1.3 
Schedule of Activities (SOA) ......................................................................................... 10 
2 
INTRODUCTION ................................................................................................................ 12 
2.1 
Study Rationale .............................................................................................................. 12 
2.2 
Background .................................................................................................................... 12 
2.3 
Risk/Benefit Assessment ................................................................................................ 14 
2.3.1 
Known Potential Risks ............................................................................................ 14 
2.3.2 
Known Potential Benefits ....................................................................................... 15 
2.3.3 
Assessment of Potential Risks and Benefits ........................................................... 15 
3 
OBJECTIVES AND ENDPOINTS ...................................................................................... 15 
4 
STUDY DESIGN.................................................................................................................. 18 
4.1 
Overall Design ................................................................................................................ 18 
4.2 
Justification for Dose ..................................................................................................... 19 
5 
STUDY POPULATION ....................................................................................................... 20 
5.1 
Inclusion Criteria ............................................................................................................ 20 
5.2 
Exclusion Criteria ........................................................................................................... 20 
5.3 
Inclusion of Vulnerable Participants .............................................................................. 21 
5.4 
Lifestyle Considerations ................................................................................................. 21 
5.5 
Screen Failures ............................................................................................................... 21 
5.6 
Strategies for Recruitment .............................................................................................. 21 
5.6.1 
Costs ........................................................................................................................ 22 
5.6.2 
Compensation ......................................................................................................... 22 
6 
STUDY INTERVENTION ................................................................................................... 23 
6.1 
Study Interventions(s) Administration ........................................................................... 23 
6.1.1 
Study Intervention Description ............................................................................... 23 
6.1.2 
Dosing and Administration ..................................................................................... 23 
6.2 
Preparation/Handling/Storage/Accountability ............................................................... 25 


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6.2.1 
Acquisition and Accountability .............................................................................. 25 
6.2.2 
Formulation, Appearance, Packaging, and Labeling .............................................. 26 
6.2.3 
Product Storage and Stability.................................................................................. 26 
6.2.4 
Preparation .............................................................................................................. 26 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................... 26 
6.4 
Study Intervention Compliance ...................................................................................... 27 
6.5 
Concomitant Therapy ..................................................................................................... 27 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................................... 28 
7.1 
Discontinuation of Study Intervention ........................................................................... 28 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................... 29 
7.3 
Lost to Follow-up ........................................................................................................... 29 
8 
STUDY ASSESSMENTS AND PROCEDURES ................................................................ 29 
8.1 
Screening Procedures ..................................................................................................... 29 
8.1.1 
Screening activities performed prior to obtaining informed consent ...................... 29 
8.1.2 
Screening activities performed after a consent for screening has been signed ....... 30 
8.2 
Efficacy Assessments ..................................................................................................... 30 
8.2.1 
Clinical Evaluations ................................................................................................ 30 
8.2.2 
Biospecimen Evaluations ........................................................................................ 30 
8.2.3 
Correlative Studies for Research Studies ................................................................ 32 
8.2.4 
Samples for Genetic/Genomic Analysis ................................................................. 33 
8.3 
Safety and Other Assessments ....................................................................................... 33 
8.4 
Adverse Events and Serious Adverse Events. ................................................................ 34 
8.4.1 
Definition of Adverse Event ................................................................................... 34 
8.4.2 
Definition of Serious Adverse Events (SAE) ......................................................... 34 
8.4.3 
Classification of an Adverse Event ......................................................................... 34 
8.4.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 36 
8.4.5 
Adverse Event Reporting ........................................................................................ 36 
8.4.6 
Serious Adverse Event Reporting ........................................................................... 37 
8.4.7 
Events of Special Interest........................................................................................ 38 
8.4.8 
Reporting of Pregnancy .......................................................................................... 38 
8.5 
Unanticipated Problems ................................................................................................. 38 


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8.5.1 
Definition of Unanticipated Problems (UP) ........................................................... 38 
8.5.2 
Unanticipated Problem Reporting ........................................................................... 38 
8.5.3 
NIH Intramural IRB Reporting of IND Safety Reports .......................................... 38 
9 
STATISTICAL CONSIDERATIONS.................................................................................. 39 
9.1 
Sample Size Determination ............................................................................................ 39 
9.2 
Populations for Analyses ................................................................................................ 39 
9.2.1 
Evaluable for toxicity .............................................................................................. 39 
9.2.2 
Evaluable for primary analysis ............................................................................... 39 
All randomized patients who heave received any study drug or placebo will be included in 
the primary outcome analysis ............................................................................................... 39 
9.3 
Statistical Analyses ........................................................................................................ 39 
9.3.1 
General Approach ................................................................................................... 39 
9.3.2 
Analysis of the Primary Endpoints ......................................................................... 39 
9.3.3 
Analysis of the Secondary Endpoint(s) ................................................................... 39 
9.3.4 
Safety Analyses ....................................................................................................... 40 
9.3.5 
Baseline Descriptive Statistics ................................................................................ 41 
9.3.6 
Planned Interim Analyses ....................................................................................... 41 
9.3.7 
Sub-Group Analyses ............................................................................................... 41 
9.3.8 
Tabulation of individual Participant Data ............................................................... 41 
9.3.9 
Exploratory Analyses .............................................................................................. 41 
10 REGULATORY AND OPERATIONAL CONSIDERATIONS ......................................... 41 
10.1 
Informed Consent Process .......................................................................................... 41 
10.1.1 Consent Procedures and Documentation ................................................................ 41 
10.1.2 Participation of Subjects who are/become Decisionally Impaired ......................... 42 
10.2 
Study Discontinuation and Closure ............................................................................ 42 
10.3 
Confidentiality and Privacy ........................................................................................ 42 
10.4 
Future use of Stored Specimens and Data .................................................................. 43 
10.5 
Safety Oversight ......................................................................................................... 43 
10.6 
Clinical Monitoring .................................................................................................... 44 
10.7 
Quality Assurance and Quality Control...................................................................... 44 
10.8 
Data Handling and Record Keeping ........................................................................... 45 
10.8.1 Data Collection and Management Responsibilities ................................................ 45 


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10.8.2 Study Records Retention ......................................................................................... 45 
10.9 
Protocol Deviations .................................................................................................... 45 
10.9.1 NIH Definition of Protocol Deviation .................................................................... 45 
10.10 
Publication and Data Sharing Policy .......................................................................... 46 
10.10.1 Human Data Sharing Plan ....................................................................................... 46 
10.10.2 Genomic Data Sharing Plan .................................................................................... 46 
10.11 
Collaborative Agreements .......................................................................................... 46 
10.11.1 Agreement Type ...................................................................................................... 46 
10.12 
Conflict of Interest Policy........................................................................................... 46 
11 ABBREVIATIONS .............................................................................................................. 47 
12 REFERENCES ..................................................................................................................... 48 
 
 
 


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STATEMENT OF COMPLIANCE 
Each engaged institution must have a current Federal-Wide Assurance (FWA) issued by the 
Office for Human Research Protections (OHRP) and must provide this protocol and the 
associated informed consent documents and recruitment materials for review and approval by an 
appropriate Institutional Review Board (IRB) or Ethics Committee (EC) registered with OHRP. 
Any amendments to the protocol or consent materials must also be approved before 
implementation.  
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 


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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
Title: 
A Phase II Study Evaluating Fostamatinib for Hospitalized 
Adults with COVID-19 
Study Description: 
This is a randomized, double-blind, placebo-controlled trial of 
fostamatinib for the treatment of hospitalized patients with COVID-
19.  
 
We will randomly assign fostamatinib or matched placebo (1:1) to  
approximately 60 eligible COVID-19 patients who are a 5 to 7 on the 
8-point scale (requiring supplemental oxygen via nasal canula or 
non-invasive ventilation, requiring mechanical ventilation or 
extracorporeal membrane oxygenation). 
 
Objectives: 
 
The primary objective of this study is to evaluate the safety of 
fostamatinib for the treatment of hospitalized patients with COVID-
19.  
 
Secondary objective will be to assess the early efficacy and clinically 
relevant endpoints of disease course  
 
Exploratory objective will be to study the host immunological 
response to COVID-19 and potential mechanism of action of 
fostamatinib 
Endpoints: 
The primary endpoint is cumulative incidence of SAEs through day 
29. 
Secondary endpoints are: 
1. Time to recovery: day of recovery is defined as the first day 
on which the subject satisfies one of the following three 
categories by Day 29: 
Ordinal scale 3: hospitalized, not requiring supplemental 
oxygen-no longer requiring ongoing medical care; 
Ordinal scale 2: non-hospitalized, limitations on activities 
and/or requiring home oxygen 
Ordinal scale 1: non-hospitalized, no limitations on activities 
2. Number of days free of mechanical ventilation [patients with 
baseline ordinal scale 5-6 only] 
3. 14-day and 28-day mortality 
4. Grade 3 and 4 AE through day 60. 
5. Days of hospitalization 
6. Ordinal scale at day 15 and day 29 


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7. Change in CRP, IL-6, d-dimer, ferritin, fibrinogen, absolute 
lymphocyte count, absolute neutrophil count, and platelet 
count from baseline [day 3, 5, 8, 11, 15, 29] 
8. Number of days in the ICU [entire hospitalization] 
9. Relative change in PaO2/FiO2 or SpO2/FiO2 ratio 
10. Change in SOFA score from baseline (day 1) [day 3, 5, 8, 11, 
15, 29] 
11. Number of days on oxygen (Including nasal canula, non-
invasive, and mechanical ventilation) 
12. Days free of renal failure [entire hospitalization]  
13. Clinically relevant deep vein thrombosis (DVT) or pulmonary 
embolism (PE) [entire hospitalization] 
Study Population: 
This trial is intended to enroll hospitalized patients with COVID-19, 
who are at least 18-years old requiring supplemental oxygen via nasal 
canula or non-invasive mechanical ventilation (5 or 6 on the 8-point 
scale) or on mechanical ventilation or ECMO (7 on the 8-point 
scale). 
Phase: 
Phase 2 
Description of 
Sites/Facilities  
Enrolling  
Participants: 
This will be a multicenter study.  Enrollment will take place at the 
NIH Clinical Center and Inova health system hospitals with the 
potential of expanding to a 3rd site. We will enroll a total of 
approximately 60 evaluable patients . The study will be conducted 
exclusively in the United States. 
 
Description of Study 
Intervention: 
The study intervention is fostamatinib, an inhibitor of spleen tyrosine 
kinase that will be administered orally at a dose of 150 mg twice 
daily for 14 days or 28 doses. Subjects will receive standard of care 
and be randomized to receive fostamatinib or matching placebo. 
 
Study Duration: 
This study will enroll over 2-3 months and it will take another 1 
month for data analysis. 
 
Participant 
Duration: 
An individual subject will complete the study in a maximum of 60 
days, from screening at Day -1 or 1 to follow-up through Day 60 ± 3 
days.  
 
 
 


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1.2 
SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hospitalized with 
COVID-19 
Recruitment/Screening 
Randomization 
Fostamatinib Arm 
+ 
Standard of Care 
Placebo Arm 
+ 
Standard of Care 
Study Blood Draws 
Capture Clinical Data 
Study Blood Draws 
Capture Clinical Data 
Survival and Adverse 
Event Follow Up 
Survival and Adverse 
Event Follow Up 
Study days 1-14 
Study days 15-60 
Study day -1 


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10  
 
 
1.3 
 
SCHEDULE OF ACTIVITIES (SOA)L 
Study Day 
-1 
1h 
2 
3 
4 
5d,
f 
6 
7 
8d,
f 
9 
10 
11d,
f 
12 
13 
14 
15c,d,f 
Daily until day 
15 if 
discharged on 
study drug or 
daily if in 
hospital until 
day 60  
22c,d,f 
29c,d,f 
60 c,d,f  
Informed Consent 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 Test 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
Xb 
Xb   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xk 
X 
X 
X 
Vital signsa 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
xi 
xi 
xi 
xi 
xi 
Physical Exam/Review of 
symptoms 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI Measurement  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ordinal Score 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SOFA Score  
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
X 
X 
 


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11  
 
Chest x-ray 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety labs: CBC, BMP, 
LFTsj 
X 
x 
 
x 
 
x 
 
 
x 
 
 
x 
 
 
 
xi 
 
xi 
xi 
xi 
Study drug  
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
Research bloods 
 
xe 
 
xe 
 
xe 
 
 
xe 
 
 
xe 
 
 
 
xe,i 
 
xe,i 
xe,i 
xe,i 
Oropharyngeal swab for viral 
RNA 
 
xe 
 
xe 
 
xe 
 
 
xe 
 
 
xe 
 
 
 
xe,i 
 
xe,i 
xe,i 
xe,i 
a) Vital signs include temperature, systolic blood pressure, heart rate, respiratory rate, and O2 saturation 
b) Can be done on day prior or day of enrollment, except SARS-CoV-2 test which can be done up to 7 days prior. 
c) If still in hospital phone visit not required. If discharged assess for adverse events, clinical status on ordinal scale, readmission, 
and mortalityCan be performed while in hospital, done as outpatient visit, or via telehealth if subject unable to travel for any 
reason. 
d) Can be performed +/- 2 days from scheduled visit 
e) Outpatient visit can be +/- 3 days from scheduled visit for days 5, 8, 11, 15, 22, 29, 60 as applictable 
f) Following discharge patients only required to return for day 15, 22, 29, and 60 follow up visits unless they are discharged on 
study drug in which they will receive daily phone calls and will be required to have safety labs drawn as scheduled on days 3, 
5, 8, 11 as applicable 
g) Day 1 is the first day of study drug 
h) Outpatient visits on day 5, 8, 11,15, 22, 29, and 60 visits are prefered as in-person visits but may be done via telehealth and 
there is no need for vital signs or scheduled sample collection when telehealth is utilized unless outpatient labs can be 
requested via outside source (example Quest)Subjects with LFTS above 3x the ULN at enrollment will have LFTs checked 
daily during the hosplitalization phase of the study.  
i) Outpatient adverse event monitoring will be performed via phone call 
j) Inpatient assesments will be done at the initial site of patient enrollment (NIH Clinical Center or Inova Health Systems.) After 
patient discharge, all outpatient assesments will be done at NIH Clinical Center, however laboratory can be done at non-NIH 
facility of patients who a having a telephone assessment.


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2 
 INTRODUCTION 
2.1 
STUDY RATIONALE 
Coronavirus Disaease-19 (COVID-19) is caused by the severe acute respiratory syndrome 
coronavirus-2 (SARS-CoV-2) and is associated with significant mortality. Currently, two 
therapies have shown efficacy in large multicenter trials for the treatment of COVID-19, one of 
which is an antiviral (remdesivir) and the other is an immunosuppressant corticosteroid meant to 
dampen the immune response (dexamethasone). This study is designed to evaluate the safety and 
early efficacy of fostamatinib in addition to standard of care for hospitalized patients with 
COVID-19. 
2.2 
BACKGROUND  
COVID-19 first described in Wuhan, China in December of 2019 and subsequently has resulted 
in a global pandemic with an excess of 3 million infections and over 130,000 deaths as of early 
July 2020 in the United States. SARS-CoV-2 primarily infects the upper and lower respiratory 
tract and can lead to acute respiratory distress syndrome (ARDS) in a subset of patients with a 
known high mortality rate. Additionally, some patients develop other organ dysfunction 
including myocardial injury, acute kidney injury, shock along with endothelial dysfunction and 
subsequently micro and macrovascular thrombosis (Berlin, Gulick & Martinez, 2020).  Much of 
the underlying pathology of SARS-CoV-2 is thought to be secondary to a dysregulated immune 
response and more recently a hypercoagulable state leading to immunothrombosis (Rapkiewicz 
et al., 2020). 
Currently, two therapies have shown efficacy in large multicenter trials for the treatment of 
COVID-19, one of which is an antiviral (remdesivir) (Beigel, 2020) and the other is an 
immunosuppressant corticosteroid meant to dampen the immune response (dexamethasone) 
("Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report", 2020). 
Meanwhile many other immunomodulators are under investigation that may provide a much 
more targeted mechanism of action than broad acting steroids, which in some patients may 
actually worsen outcomes.  
Spleen tyrosine kinase (SYK) is a cytoplasmic tyrosine kinase involved in the intracellular 
signaling pathways of many different immune cells. In this pilot study we propose to use 
fostamatinib (a SYK inhibitor) as a targeted therapy for the immunological complications of 
hospitalized patients with COVID-19. The biological mechanisms by which SYK inhibition may 
improve outcomes in patients with COVID-19 include the inhibition of pro-inflammatory 
cytokines by monocytes and macrophages, decreased production of neutrophil extracellular traps 
(NETs) by neutrophils, and inhibition of platelet aggregation; three pathways that are mediated 
through Fc receptors (FcR) recognition of antigen-antibody complexes or activation of c-type 
lectin receptors (CLEC) (Hoepel et al., 2020). 
It is noted that a primary driver of SYK signaling is through the FcγRIIA which is driven by 
immune antigen-antibody complex. It is becoming increasing clear that there is an exuberant 
antibody response in patients with severe disease compared to those with less severe disease, a 
response that may be driven by viral load. By blocking this immune response, it is possible that 
fostamatinib may improve outcomes of patients with COVID-19. More specifically, in 


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monocytes and macrophages SYK is known to mediate the pro-inflammatory process through 
the production of pro-inflammatory cytokines such as IL-6. The production of pro-inflammatory 
cytokines has been reversed with the inhibition of SYK in MERS-CoV infected macrophages 
(Zhao et al., 2019). A recent study also found that anti-Spike IgG from serum of severely ill 
COVID-19 patients induces a hyperinflammatory response by human macrophages including 
elevated levels of IL-1β, IL-6, IL-8, TNF, and IL-10, a response that can be counteracted by 
SYK inhibition with fostamatinib. Furthermore, this study found that anti-Spike IgG is able to 
break down pulmonary endothelial barriers and induce microvascular thrombosis as evidenced 
by increase platelet adhesion and expression of von Willebrand’s factor (Zhao et al., 2019). 
In addition to the inhibition of the hyperinflammatory response from stimulated macrophages 
SYK inhibition of neutrophils and platelets may lead to decreased immunothrombosis resulting 
in less organ dysfunction in many patients with COVID-19 who become critically ill.  In 
neutrophils SYK inhibition can lead to decreased production of neutrophil extracellular traps 
(NETs) which are known to be a driver of microthrombosis in heparin-induced 
thrombocytopenia, a process that is provoked by antigen-antibody complex stimulation of the Fc 
receptor (Zhao et al., 2019).  In platelets SYK in known to inhibit multiple pathways associated 
with platelet aggregation including FcγRIIA activation by immune complex, GPVI activation by 
collagen, and CLEC-2 activation by rhodocytin, all while not affecting ADP mediated platelet 
aggregation. By decreasing NET production and inhibiting platelet aggregation, SYK inhibition 
may lead to decreased immunothrombosis potentially decreasing organ dysfunction in patients 
with COVID-19 and ultimately improving outcomes.  
Lastly, fostamatinib was identified in a screen of 3,373 compounds in different stages of 
development to reduce mucin-1 (MUC1) expression, a membrane bound molecule expressed on 
the apical surfaces of epithelial cells and a marker associated with increased severity of ARDS. 
In this study fostamatinib reduced MUC1 expression in lung epithelial cells in a mouse model of 
acute lung injury, providing additional rational for why it may be advantageous in patients with 
COVID-19 ARDS (Alimova et al. 2020). 
Fostamatinib is FDA approved in the US for the treatment of thrombocytopenia in adult patients 
with chronic immune thrombocytopenia (ITP) who have had insufficient response to a previous 
treatment and additionally, there is extensive experience with this drug in patients with 
rheumatoid arthritis (Weinblatt et al., 2008). Previous clinical reports support the clinical use of 
fostamatinib by showing it decreases interleukin-6 level in rheumatoid arthritis patient. Also, 
animal models using lipopolysaccharide induced inflammation have demonstrated that 
fostamatinib decreases acute lung injury and acute kidney injury (Al-Harbi et al., 2019) (Nadeem 
et al., 2019), making fostamatinib a candidate for the treatment of COVID-19. To date 
fostamatinib has not been used for the treatment of COVID-19. In light of overlapping toxicity 
between fostamatinib and other treatment modalities along with the clinical presentation of 
COVID-19 that can have significant overlap with the toxicities of fostamatinib we seek to 
perform a double blinded placebo control randomized clinical trial to test primarily safety of this 
drug in this hospitalized population.  


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2.3 
RISK/BENEFIT ASSESSMENT 
2.3.1 Known Potential Risks 
Potential Risks of Fostamatinib: 
Fostamatinib is FDA approved for the treatment of thrombocytopenia in adult patients 
with chronic immune thrombocytopenia (ITP) who have had an insufficient response 
to a previous treatment (FDA label 2020). To date, over 4,800 patients have received 
fostamatinib as part of randomized controlled and open label trials across a variety of 
disease states including rheumatoid arthritis, ITP, autoimmune hemolytic anemia, and 
oncologic diseases. It has a consistent safety profile and the most common adverse 
reactions (≥5% and more than placebo) are diarrhea, hypertension, nausea, respiratory 
infection, dizziness, ALT/AST increased, rash, abdominal pain, fatigue, chest pain and 
neutropenia. Warnings and precautions included in the US product label include 
hypertension, elevated liver function tests, diarrhea, neutropenia, and embryo-fetal 
toxicity. 
Hypertension 
Hypertensive crisis occurred in 1% of patients and patients with pre-
existing hypertension may be more susceptible 
Hepatotoxicity 
AST/ALT levels more than 3x the upper limited of normal occurs in 
9% of patients  
Diarrhea 
Occurred in 31% of patients treated with severe diarrhea occurring 
in 1% 
Neutropenia 
Occurred in 6% of patients with febrile neutropenia occurring in 1% 
Embyro-fetal toxicity 
Based on findings from animal studies and mechanism of action 
fostamatinib can cause fetal harm.  
Concomitant use with strong CYP3A4 inhibitors with fostamatinib will increase exposure to 
R406 that may result in increased risk of adverse reactions while concomitant use of strong 
CYP3A4 inducers reduces exposure to R406. Fostamatinib may increase the concertation of 
some CYP3A4 substrate drugs, some BCRP substrate drugs (ex. rosuvastatin), and some P-
glycoprotein substrate drugs (eg. Digoxin). 
It is not expected that there will be additive or synergistic adverse events with the addition of 
fostamatinib with standard of care except for remdesivir, which can cause increase in AST/ALT. 
In addition to the fostamatinib adverse reactions listed above, the major potential risks of this 
study relate to the underlying disease (COVID-19) which has a high associated mortality in 
hospitalized patients. All subjects will be asked to provide personal identifiable information 
(PII). While every effort will be made to keep PII confidential, there is a chance PII may be 
obtained by unauthorized personnel. Electronic files will be password protected and all files will 
be locked in a cabinet or maintained in a locked room at the participating clinical site. Any 
publication will not have identifying information.  


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2.3.2 Known Potential Benefits 
Fostamatinib may or may not improve the clinical outcome of individuals with COVID-19. 
However, there is benefit to society for their participation and insights may be gained about the 
therapeutic intervention under study. Additionally, individuals may benefit from a shortened 
disease course if fostamatinib is successful in this clinical trial.  
2.3.3 Assessment of Potential Risks and Benefits 
Fostamatinib has a consistent safety profile and adverse events are clearly documented. 
Currently the only immunomodulating therapy that has proven benefit in patients with COVID-
19 is dexamethasone which improved mortality from 24.6% to 21.6% (RR 0.80, 95% CI 0.74-
0.92, p=<0.001) when compared to usual care in patients with COVID-19. This improvement in 
mortality was more dramatic in patients who required mechanical ventilation where mortality 
improved from 40.7% to 29.0%, resulting in a need to treat 8 patients to show benefit in one. 
However, the high mortality rate in the control group compared to usual care in the United 
States, the multiple randomizations permitted, and lack of remdesivir as part of usual care make 
interpreting the results of this study for patients in the United States difficult. Furthermore, the 
mechanism of action by which dexamethasone would improve outcomes is not known as steroids 
have indiscriminate broad ranging effects on immunosuppression.  Fostamatinib has many 
potential advantages over steroids including a targeted mechanism of action that inhibits multiple 
pathways in the pathogenesis of COVID-19 including decreasing Fc receptor signaling on 
neutrophils, monocytes and macrophages and CLEC receptors on neutrophils and platelets. 
Through these mechanisms we hypothesize that fostamatinib will decrease the 
immunodysregulation associated with COVID-19 along with the NETosis and inflammatory 
driven immunothrombosis that precedes much of the organ failure.  
 
3 
OBJECTIVES AND ENDPOINTS 
The primary objective of this study is to evaluate the safety of fostamatinib for the treatment of 
hospitalized patients with COVID-19.   
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
To 
assess 
the 
safey 
of 
fostamatinib in hospitalized 
patients with COVID-19 
Cumulative incidence of SAEs 
through day 29. 
 
This endpoint was 
chosen to evaluate the 
safety of fostamatinib 
for the treatment of 
hospitalized patients 
with COVID-19. 
Secondary 
 
 


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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
To assess the effect of 
fostamatinib on clinically relevant 
endpoints of disease course  
1. Time to recovery by day 29: 
day of recovery is defined as 
the first day on which the 
subject satisfies one of the 
following three categories: 
Ordinal scale 3: hospitalized, 
not requiring supplemental 
oxygen-no longer requiring 
ongoing medical care;     
Ordinal scale 2: non-
hospitalized, limitations on 
activities and/or requiring home 
oxygen;                            
Ordinal scale 1: non-
hospitalized, no limitations on 
activities 
2. Number of days free of 
mechanical ventilation [patients  
with baseline ordinal scale 5-6 
only] 
3. Mortality at day 14 and 28 
4. Grade 3 and 4 AE through 
day 60 
5. Days of hospitalization 
6. Ordinal scale at day 15 and day 
29 
7. Change in CRP, IL-6, ferritin, 
d-dimer, fibrinogen, absolute 
lymphocyte count, absolute 
neutrophil count, and platelet 
count from baseline [day 3, 5, 
8, 11, 15, 29] 
8. Number of days in the ICU 
[entire hospitalization] 
9. Relative change in PaO2/FiO2 
or SpO2/FiO2 ratio 
10. Change in SOFA score from 
baseline (day 1) [day 3, 5, 8, 11, 
15, 29] 
11. Number of days on oxygen 
(Including nasal canula, HFNC, 
non-invasive, and mechanical 
ventilation) 
12. Days free of renal failure [entire 
hospitalization]  
Each of the secondary 
clinical endpoints were 
deemed to be clinically 
relevant indicates for 
improved or worsening 
disease course  


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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
a. Renal failure defined as 
i. Increase in serum 
creatinine by ≥0.3mg/dL 
within 48 hours or 
ii. Increase in serum 
creatinine by ≥1.5 times 
baseline which is known 
or presumed to have 
occurred within the prior 
seven days, or 
13. Clinically relevant deep vein 
thrombosis (DVT) or 
pulmonary embolism (PE) 
[entire hospitalization] 
 
Tertiary/Exploratory  
 
 
1) To study the host 
immunological response to 
COVID-19 and potential 
mechanism of action of 
fostamatinib. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
As an exploratory endpoint we will 
study the immune mechanism by which 
fostamatinib improves outcomes in 
patients with COVID-19. 
1. Characterization of plasma 
biomarkers of immune 
activation 
2. Measure platelet-leukocyte 
aggregates 
3. Measure leukocyte activation 
assays 
4. Measure plasma cytokine and 
chemokine levels 
5. Evaluate the coagulation 
cascade 
6. Measurement of immune 
antigen-antibody complexes  
7. Measure thromboelastography 
(TEG) 
8. Measure biomarkers of 
endothelial dysfunction 
9. Characterize leukocyte 
extracellular traps 
10. SARS-CoV-2 viability via 
cell culture from 
oropharyngeal samples 
These exploratory 
endpoints are relevant 
ex vivo and in vitro 
analysis that will help 
determine disease and 
mechanisms of action 
while on fostamatinib 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
 
11. Detection of viral antigen 
blood and oropharyngeal 
samples  
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
We intend to study fostamatinib for the treatment of hospitalized patients with COVID-19.  
• This will be a multicenter, randomized, double-blind, placebo-controlled, phase 2  
trial with the objective to evaluate the safety of fostamatinib compared to 
matching placebo in COVID-19 patients who are hospitalized with a 5, 6, or 7 on 
the 8-point ordinal scale.  
• The NHLBI will be the Coordinating Center for this multicenter study. All 
participating sites will enroll and treat subjects as described below.  Research labs 
for exploratory endpoints will be processed at participating sites or shipped to the 
NIH Clinical Center for processing. 
• All study participants will receive standard of care throught the entire study and 
then will be randomizd to 150 mg of fostamatinib twice a day or placebo for 14 
days (total 28 doses). 
• Subjects will be assessed daily while hospitalized and followed until day 60. If 
patients improve and are discharged prior to day 14 the study drug will be 
continued until day 14 as an outpatient. Patients who are discharged on study drug 
will receive a phone call daily to assess for adverse events and will have safety 
labs drawn on days 3, 5 8, 11 as applicable (outpatient third party lab aquisition 
may be utilized as needed). We will make every effort to bring back discharged 
patients for outpatient visits on days 15, 22, 29, and 60 to include laboratory 
draws. In patients who are unable to follow-up, they will receive a telephone visit 
as a follow up.  
• Day 1 of study is the first day of study drug and patients will be followed until 
day 60. 
 
8-point ordinal scale for secondary endpoint of efficacy and stratification (World Health 
Organization 2020) 
Scale 
Description 
8 
Death 
7 
Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane 
oxygenation (ECMO) 


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6 
Hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices 
5 
Hospitalized, requiring any supplemental oxygen 
4 
Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care 
(COVID-19–related or other medical conditions) 
3 
Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical 
care (used if hospitalization was extended for infection-control reasons) 
2 
Not hospitalized, limitation of activities, home oxygen requirement, or both 
1 
Not hospitalized, no limitations of activities 
Standard of Care: 
For the purposes of this study standard of care is defined primarily as remdesivir as an antiviral 
intended to decrease viral load and dexamethasone a broad-spectrum anti-inflammatory intended 
to dampen the immune response to SARS-CoV-2. However, it is noted that in the middle of a 
pandemic evidence for and against specific therapies for the treatment of COVID-19 continue to 
evolve and therefore standard of care may change throughout this study. At the current time once 
enrolled, use of any biologic therapy outside of local standard of care are prohibited. This 
includes monoclonal antibodies targeting cytokines (e.g., TNF inhibitors; interleukin-1[IL-1], IL-
6 [tocilizumab or sarilumab]), or T-cells (e.g., abatacept); monoclonal antibodies targeting B-
cells (e.g., rituximab in the last 6 months, and including any targeting multiple cell lines 
including B-cells); JAK inhibitor(s) other than baricitinib (e.g., imatibib, genfinitib); and 
interferon, plasma, or immunoglobulin (IgG) therapies for COVID-19 are not permitted. 
However, if patient has a clinical deterioration while on fostamatinib rescue therapies above 
including convalescent plasma may be considered. Additionally, if a specific site has a change in 
their standard of care outside of remdesivir and dexamethasone these medications will be 
permitted.  
This study is randomized placebo-controlled study. All patients will receive standard of care 
described above. 
4.2 
JUSTIFICATION FOR DOSE 
The dose of 150 mg twice daily is based on the safety and efficacy of fostamatinib from others 
trials. For chronic immune thrombocytopenia fostamatinib is initially started at a dose of 100 mg 
twice daily and up titrated to a maximum dose of 150 mg twice daily to achieve the goal of 
platelets above 50x109/L while utilizing lowest possible dose to achieve that goal. Because the 
treatment duration of fostamatinib in this study may be only 14 days and we are interested in 
inhibition of the dysregulated immune response, we will start the study drug at the higher dose of 
150 mg twice daily. 
 


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5 
STUDY POPULATION 
Subject Inclusion and Exclusion Criteria will be reviewed as appropriate by a member of the 
study team. If there is any uncertainty, the PI should make the decision on whether a potential 
subject is eligible for study enrollment. There is no exclusion for receipt of SARS-CoV-2 
vaccine (experimental or licensed).  
5.1 
INCLUSION CRITERIA 
1. Patient must be hospitalized, or had their inpatient stay extended, for COVID-19. 
2. Age ≥18 years 
3. Subject (or legally authorized representative) provides informed consent prior to 
initiation of any study procedures. 
4. Subject (or legally authorized representative) understands and agrees to comply with 
planned study procedures. 
5. Females of childbearing potential must agree to be abstinent or use a medical acceptable 
form of contraception from the time of enrollment through 30 days after last day of study 
drug 
6. Laboratory confirmed SARS-CoV-2 RT-PCR test within 7 days of enrollment 
7. Illness of any duration with SpO2 of less than 94% on room air requiring supplemental 
oxygen via nasal canula or non-invasive mechanical ventilation, or mechanical 
ventilation or ECMO (5 to 7 on the 8-point scale) 
5.2 
EXCLUSION CRITERIA 
1. ALT or AST > 5 times the upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and 
total bilirubin > 2 × ULN. 
Estimated glomerular filtration rate (eGFR) <30ml/min  
2. Pregnancy or breast feeding 
3. Anticipated discharge in the next 72 hours 
4. Allergy to study medication 
5. Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood 
pressure >100mmHg) 
6. Shock or hypotension at the time of enrollment 
7. Neutrophil count <1000/µL 
8. Concern for bacterial or fungal sepsis 
9. Received immunomodulatory treatment within 30 days prior to enrollment e.g., Bruton’s 
tyrosine kinase/phosphoinositide 3 kinase/Janus kinase inhibitor or cytokine-targeting 
biologic therapy (anti-TNF, IL-6), or B-cell depleting antibody in the prior 6 months 
(rituximab, other anti-CD20 mAb) 
10. Received a live vaccine the last 4 weeks 
11. Those who were cognitively impaired or mentally disabled prior to COVID diagnosis 
1.1 
INCLUSION OF VULNERABLE PARTICIPANTS 
 
12. Participation in another clinical trial for the treatment of COVID-19. 


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5.3 
INCLUSION OF VULNERABLE PARTICIPANTS 
Certain human subjects are categorized as vulnerable populations and require special treatment 
with respect to safeguards of their well-being. For this clinical trial, examples include intubated 
individuals who are sedated. When it is determined that a potential research subject is 
cognitively impaired, federal and institutional regulations permit researchers to obtain consent 
from a legally authorized representative (LAR). The study team will obtain consent from these 
vulnerable subjects using an IRB-approved protocol- specific process for consent using a LAR.  
For subjects for whom a LAR gave consent, during the course of the study, if the subject regains 
the capacity to consent, informed consent must be obtained from the subject and the subject 
offered the ability to leave the study if desired.  
It is particularly important to include patients who may be sedated while on mechanical 
ventilation or extracorporeal membrane oxygenation because they are they patients who have 
suffered the most severe complications of this disease.  
5.4 
LIFESTYLE CONSIDERATIONS 
Study participant should refrain from drinking alcohol while taking study drug. 
Once discharged, subjects of child bearing potential should avoid pregnancy through abstinence 
or use of at least one contraceptive until 30 days after last day of study drug. 
5.5 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently assigned to the study intervention or entered in the study because the 
participants did not meet the trial eligibility or withdrew consent. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants, to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this trial (screen failure) may be 
rescreened once. Rescreened participants should be assigned the same participant number as for 
the initial screening. 
 
5.6 
STRATEGIES FOR RECRUITMENT  
This is a multi-site study and subjects will be enrolled at the NIH Clinical Center, Inova Fairfax 
and Alexandria hospitals. Hospitalized participants will be recruited from within NIH and from 
the Inova hospitals.  
A written strategic recruitment plan will be authored by the NHLBI Patient Recruitment Office 
(PRO) and ongoing regular recruitment-focused meetings will be held with the PRO and study 
staff and partners to ensure the study is meeting enrollment projections. If enrollment projections 


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are not being met, a strategy to boost enrollment will be implemented, and may include local 
news media coverage and live social media events. 
Source of participants include inpatient hospital setting, outpatient clinics, and general public. 
The participants may also be recruited via self-referral, from in-patient services of regional 
hospitals and from outpatient settings.  
Participants may be recruited through the use of: 
• Flyers, documents/info cards, etc. for in-hospital use with patients and family;  
• Recruitment advertisements and writeups placed in the NIH Record, NIH websites, the 
Clinical Center News; 
• ResearchMatch.org; 
• Newspaper writeups (print and digital) in local newspapers or outlets;  
• NIH email listservs; 
• Media interviews with investigators;  
• NIH social media on Facebook and/or Twitter; 
• ClinicalTrials.gov, Clinical Center “Search the Studies” website, NHLBI website, and 
NIH CC study recruitment page facilitated by CC communications office;  
• Paid, targeted advertising, including digital social media ads, to local public population 
may be done led by the NHLBI digital communications specialist.  
• A letter to physicians about the study may be provided to area ICUs and hospitalist 
groups.  
• Hospital partners will be provided with written study materials, and in-service sessions 
by the study PI to educate and inform about the study. 
There are no restrictions based on gender, race or ethnicity, or non-English speaking subjects. 
All advertising/recruitment language will be IRB reviewed/approved prior to posting/using. 
Recruitment materials may be translated from English into other languages, including Spanish. 
Anticipated accrual rate is approximately 25 patients per month. 
5.6.1 Costs 
There are no costs associated to this study for subjects treated at the NIH. 
By virtue of NHLBI sponsorship of clinical research protocols, enrolling sites qualify for Centers 
for Medicare and Medicaid Services (CMS) coverage of associated routine costs of medical care 
under the CMS Clinical Trial Policy (CTP). This policy is detailed at 
https://www.cms.gov/Medicare/Coverage/ClinicalTrialPolicies/index.html.  According to this 
policy, CMS is explicitly authorized to provide payment for routine patient care costs and costs 
due to medical complications associated with participation in clinical trials.  
5.6.2 Compensation 
Study subjects will be compensated for outpatient phlebotomy and follow up visits that occur at 
the NIH as follows: 
• $50 for each blood draw; 


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• $20 for your first hour, and $10 for each subsequent hour spent at NIH Clinical Center 
during the follow up visit. 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTIONS(S) ADMINISTRATION 
All patients will be randomized to receive fostamatinib or matching placebo. All patients will 
receive standard of care.  
6.1.1 Study Intervention Description 
Patients hospitalized with COVID-19 on oxygen will receive fostamatinib at a dose of 150 mg 
twice daily for 14 days or placebo. Patients who are discharged prior to completing a 14 day 
course will continue therapy as an outpatient. 
Fostamatinib is a spleen tyrosine kinase inhibitor that is currently FDA approved for the 
treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) 
who have had an insufficient response to a previous treatment.  
The use of fostamatinib for the proposed indication is investigational and the study will be 
conducted under FDA IND # 152131. 
Fostamatinib is a prodrug with an active metabolite, R406, which is known to inhibit Fc-
activating receptors and B-cell receptors. R406 is protein bound and has a half-life of 15 hours, 
with 80% of excretion occurring in feces and 20% excreted in urine. 
Concomitant use with strong CYP3A4 inhibitors with fostamatinib will increase exposure to 
R406 that may result in increased risk of adverse reactions while concomitant use of strong 
CYP3A4 inducers reduces exposure to R406. Fostamatinib may increase the concertation of 
some CYP3A4 substrate drugs, some BCRP substrate drugs (ex. rosuvastatin), and some P-
glycoprotein substrate drugs (eg. Digoxin). 
6.1.2 Dosing and Administration 
All patients will start fostamatinib or matched placebo at a dose of 150 mg orally twice daily for 
a total of 14 days (28 scheduled doses) to be swallowed as an oral tablet. If necessary, tablets can 
be crushed until granular with an approximate particle size <2 mm, added to approximately 10 
mL of water, and stirred to mix before administration through the orogastric or nasogastric tube. 
Dose modifications based on adverse reactions are described in section 6.1.2.3 
6.1.2.1 Dose Escalation 
N/A 
6.1.2.2 Dose Limiting Toxicity 
N/A 
6.1.2.3 Dose Modifications 
Adverse Reaction 
Recommended action  
Hypertension 
 


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Stage 1: systolic between 130-139 or diastolic 
between 80-89 mmHg 
Initiate or increase antihypertensive 
medication for patients with increased risk of 
cardiovascular risk, and adjust as needed. No 
dose modification to study drug required.  
Stage 2: systolic at least 140 or diastolic at 
least 90 mmHg 
Initiate or increase antihypertensive 
medication and adjust as needed until BP 
control. No dose modification to study drug 
required. 
Hypertensive crisis: systolic over 180 and or 
diastolic over 120 mmHg 
Discontinue study drug until blood pressure is 
below systolic blood pressure of 160 and 
diastolic less than 100 mmHg. When 
restarting study drug dose should be reduced 
to 100 mg twice daily or matching placebo for 
the remainder of the study 
Hepatotoxicity 
 
Increase in AST/ALT by x3 from level at the 
time of enrollment  
Stop study drug and recheck liver function 
tests the next day. May restart when 
AST/ALT have returned to less than 3x 
baseline. When restarting study drug dose 
should be reduced to 100 mg twice daily or 
matching placebo for the remainder of the 
study*  
Increase in AST/ALT to 3X ULN and total 
BL (bilirubin) greater than 2 x upper limit of 
normal (ULN) 
Stop fostamatinib and recheck liver function 
tests the next day. May restart when 
AST/ALT have returned to less than 3x ULN 
and total BL has returned to less than 2x 
upper ULN. When restarting study drug dose 
should be reduced to 100 mg twice daily or 
matching placebo for the remainder of the 
study* 
Elevated unconjugated (indirect) BL in 
absence of other LFT abnormalities  
 
Continue study drug with frequent monitoring 
since isolated increase in unconjugated 
(indirect) bilirubin may be due to UGT1A1 
inhibition  
Diarrhea 
 
Diarrhea 
Manage diarrhea using supportive measures 
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antidiarrheal medication) early after the onset 
until symptoms resolve. 
If symptoms become severe (grade 3) or 
above), temporarily stop study until 
symptoms resolve to mild (grade 1). When 
restarting study drug dose should be reduced 
to 100 mg twice daily or matching placebo for 
the remainder of the study 
Neutropenia 
 
Neutropenia 
If absolute neutrophil count decreases (ANC 
less than 1.0x10^9/L) discontinue 
fostamatinib. When ANC returns to above 
1.0x10^9/L, restart study drug. When 
restarting study drug dose should be reduced 
to 100 mg twice daily or matching placebo for 
the remainder of the study 
*Parameters and laboratory abnormalities must resolve within 3 days to restart the study drug.   
6.1.2.4 Drug Administration 
Study drug may be taken with or without food. In the case of a missed dose of study drug 
subjects should take their next dose at its regularly scheduled time. For patients able to swallow 
medication should be taken orally. For patients who are unable to swallow, on mechanical 
ventilation or on EMCO drug should be crushed and provided via nasogastric or orogastric 
access. Tablets should be crushed until granular with an approximate particle size <2 mm, added 
to approximately 10 mL of water, and stirred to mix before administration through the orogastric 
or nasogastric tube 
If a subject is discharged from the hospital and then readmitted prior to Day 14, they may be 
given the remainder of the same study product up until day 14 that they were taking as an 
outpatient already. If the subject did not withdraw his/her consent to participate in the study, 
there is no need to reconsent upon readmission to the study hospital. The study team will need to 
notify the study pharmacist of the readmission. No study medication should be given past Day 14 
(total 28 doses).  
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY  
6.2.1 Acquisition and Accountability 
Investigational product (IP) will be shipped to the site either directly from Rigel 
Pharmaceuticals, or from other regional or local drug repositories. All other supplies should be 
provided by the site. Multiple lots of IP may be supplied.  


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Study products received at the sites will be open label unless specified in the protocol-specific 
pharmacy manual. Drug preparation will be performed by the participating site’s unblinded 
research pharmacist on the same day of administration to the subject.  
The site PI is responsible for study product distribution and disposition and has ultimate 
responsibility for study product accountability. The site PI may delegate to the participating 
site’s research pharmacist responsibility for study product accountability. The participating site’s 
research pharmacist will be responsible for maintaining complete records and documentation of 
study product receipt, accountability, dispensation, storage conditions, and final disposition of 
the study product(s).  
6.2.2 Formulation, Appearance, Packaging, and Labeling 
Fostamatinib will be provided by Rigel Pharmaceuticals and stored in the pharmacy of each 
participating hospital.  The drug product consists of 2 strengths of orange film-coated, plain, 
bioconvex tablets. The 150 mg tablet is oval and the 100 mg tablet is round.  The tablets are 
supplied in white opaque high-density polyethylene bottles capped with white 
polypropylene child resistant closures with foil induction seals. Placebo tablets to match 
fostamatinib 100 mg and 150 mg will be provided by Rigel. 
 
6.2.3 Product Storage and Stability 
Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 
30°C (59°F to 86°F). Do not remove desiccants.  
6.2.4 Preparation 
For patients who are unable to take oral medication tablets should be crushed until granular with 
an approximate particle size <2 mm, added to approximately 10 mL of water, and stirred to mix 
before administration through the orogastric or nasogastric tube 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
6.3.1  Randomization 
The study will randomize subjects 1:1 to placebo or fostamatinib.  Once a subject has completed 
the screening and baseline period and evaluation for inclusion/exclusion criteria, the 
randomization process will begin.  The site investigator or designee will obtain the randomized 
assignment for that subject from the data coordinating center.  Randomization will be stratified 
by site and severity of illness at enrollment. Severity of illness will be stratified into ordinal scale 
5 and 6 (supplemental oxygen via nasal canula or non-invasive ventilation), mechanical 
ventilation, and ECMO.  
6.3.2  Blinding and Masking Procedures 
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The fostamatinib and matched placebo is blinded.  Fostamatinib and placebo tablets are identical 
in appearance. 
Unblinding of the study will occur after all subjects enrolled have reached the end of study, and 
these visits are monitored and data is cleaned, or if the DSMB recommends unblinding. 
If AEs occur and investigators are concerned about the treatment allocation, the treatment can be 
discontinued. If a Serious Adverse Event occurs, that is thought to be related to the study drug, 
and the treating clinician believes that knowledge of the treatment arm may change the therapy 
provided to the patient, the individual subject can be unblinded 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
During the inpatient phase of the study each dose of study product will be administered by a 
member of the clinical care team who is qualified and licensed to administer the study product. 
Administration, date, and time will be entered into the appropriate case report form (CRF).  
If a patient is discharged prior to day 14, study drug supply will be given to the patient to be 
taken at home up until day 14, for a total of 28 doses. The participant compliance will be 
monitored by pill counts at the day 15 visit. If this visit takes place remotely via telehealth, the 
investigator will observe the research subject counting the remaining pills. The quantity of taken 
drug,  date, and time will be entered into the appropriate case report form (CRF). 
 
 
6.5 
CONCOMITANT THERAPY 
For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported in the CRF are 
concomitant prescription medications, over-the-counter medications and supplements used for 
the treatment of COVID-19.  
For patients that are eligible for the study, other therapy received prior to enrollment with any 
other experimental treatment or off-label use of marketed medications that are intended as 
specific treatment for COVID-19 or the SARS-CoV-2 infection not identified in the exclusion 
criteria are permitted but must be discontinued on enrollment.  
In patients who have clinical deterioration while on fostamatinib any rescue or investigational 
therapy that a provider thinks may benefit a patient may be administered (e.g. tocilizumab and 
convalescent plasma). Administration of these drugs will be tracked via the CRF.  
Venous thromboembolism (VTE) prophylaxis is recommended for all patients unless there is a 
major contraindication such as active bleeding events or history of heparin-induced thrombosis.  
Concomitant medications will be assessed only from 7 days prior to enrollment through 
discharge. Report all prescription medications taken during this time period.  


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Do not report vitamins, herbal supplements, or topical medications. Do not report over-the- 
counter cold medicines and antipyretics that the subject reportedly took at home prior to 
hospitalization.  
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL  
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Study product administration for any given subject may be stopped for SAEs, clinically 
significant adverse events, severe laboratory abnormalities, or any other medical conditions that 
indicate to the Investigator that continued dosing is not in the best interest of the patient.  
See section 6.1.2.3 for information on dosing modifications or discontinuation rules based on 
laboratory abnormalities or other adverse events. 
Subjects who have the study product stopped for a safety related issues will not continue with 
dosing. In addition, subjects who have an allergic reaction that is temporally associated with 
study product administration and the PI believes it to be related to study product will not receive 
any more study product.  
In addition, a subject in this clinical study may discontinue study drug at their request for any 
reason. Every effort should be made to encourage subjects to remain in the study for the duration 
of their planned outcome assessments. Subjects should be educated on the continued scientific 
importance of their data, even if they discontinue study drug.  
Unless the subject withdraws consent, those who discontinue study drug early will remain in the 
study. The reason for subject discontinuation of study drug should be documented in the CRF.  
Discontinuation from the study drug does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study protocol.  If a 
clinically significant finding is identified (including, but not limited to changes from baseline) 
after enrollment, the investigator or qualified designee will determine if any change in participant 
management is needed. Any new clinically relevant finding will be reported as an adverse event 
(AE). 
The data to be collected at the time of study intervention discontinuation will include the 
following: 
• Reason for discontinuation 
• Date of last study drug administration  
• Any adverse event  
• Patients will be followed for clinical data required for the duration of the study  
Participants are free to withdraw from participation in the study at any time upon request. 
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• Disease progression which requires discontinuation of the study intervention 
• 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 
• Positive pregnancy test 
• Participant unable to receive study drug 
• Lost to Follow Up 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request.  
Subjects who withdraw from this study or are lost to follow-up after signing the informed 
consent form and administration of the study product, will not be replaced. The reason for 
subject withdrawal from the study will be recorded on the appropriate CRF. 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for a scheduled visit 
and is unable to be contacted by the study site staff.  
The following actions must be taken to maximize study subject retention and prevent missing 
data if a participant fails to return to the clinic for a required study visit: 
• The site will attempt to contact the participant and reschedule the missed visit within 2 
days of the visit and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain if the participant wishes to and/or should continue in 
the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls). 
These contact attempts should be documented in the participant’s medical record or study 
file.  
• Should the participant continue to be unreachable, the clinical team will try to ascertain 
vital status through vital record search; and the participant will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
SCREENING PROCEDURES 
8.1.1 Screening activities performed prior to obtaining informed consent 
Minimal risk activities that may be performed before the subject has signed a consent include the 
following:  
• Review of existing medical records to include H&P, laboratory studies, etc.   
• Review of existing MRI, x-ray, or CT images. 
• Review of SARS CoV-2 test results. 


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8.1.2 Screening activities performed after a consent for screening has been signed 
The following activities will be performed only after the subject has signed the consent this 
study.  
• Physical examination 
• Pregnancy test (for female subjects of childbearing age) 
• Clinical labs (CBC, liver enzymes panel, chemistry panel), if not available 
• X-ray, if not available 
The overall eligibility of the subject to receive the study drug will be assessed once all screening 
values are available and completion of an eligibility checklist. 
8.2 
EFFICACY ASSESSMENTS 
For all baseline assessments and follow-up visits, refer to the Schedule of Assessments (SOA) 
for procedure to be done, and details below for each assessment.  
Inpatient assesments will be done at the initial site of patient enrollment (NIH Clinical Center or 
Inova Health Systems.) After patient discharge, all outpatient assesments will be done at NIH 
Clinical Center either in person or remotely using NIH approved TeleMedicine software and 
approved NIH TeleMedicine guidance. 
The subject’s clinical status will be captured on each study day while hospitalized up until and 
including Day 60. If a subject is discharged prior to Day 15, clinical status is captured on Day 
5,8,11, 15, 22, 29, and 60 if the subject returns for an in-person clinic visit or by phone or 
telehealth if an in-person visit is not possible. Clinical status will also be captured on Day 22 
during a phone or telehealth visit. Clinical status is defined by secondary outcomes.  
8.2.1  Clinical Evaluations 
Physical examination: A baseline physical examination will be performed prior to initial study 
product administration on Day 1. The baseline physical examination can be one that is conducted 
from screening to Day 1. Post-baseline physical examinations will be done only when needed to 
evaluate possible adverse event(s) (i.e. any new signs or symptoms). No routine physical exam is 
needed for study visits after Day 1.  
Radiographic or other imaging assessments. Chest x-ray are to be done at day 1 and repeated 
as clinically indicated.  
8.2.2 Biospecimen Evaluations 
Research bloods will be sent from Inova hospitals to the NIH for processing in either the clinical 
laboratory -or  in a NHLBI research lab.  
The amount of blood that may be drawn from subjects for research purposes shall not exceed 
10.5 mL/kg or 550 mL, whichever is smaller, over any eight-week period. 
 


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Test/assay 
Volume 
blood 
(approx.) 
Type of tube 
Frequency**** 
Location of 
specimen analysis 
Routine*  
• 
CBC 
 
• 
BMP 
• 
Hepatic 
 
3 mL 
 
4 mL 
 
EDTA tube 
(lavender) 
 
Lithium Heparin 
tube (light green)  
 
 
Baseline (prior to 
enrollment) 
D1-entire 
hospitalization, 
D15, D22, D29, 
D60 if outpatient 
 
Clinical Lab 
At participating 
sites 
Research* 
• 
PT 
• 
PTT 
• 
INR 
• 
Fibrinogen 
• 
D-dimer  
• Von Willebrand 
factor 
 
3 ml  x2 
 
 
Sod Citrate (BLU) 
x2 
 
 
 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
 
NIH Clinical Lab 
 
 
 
 
Research* 
• 
P-selectin 
• Thrombomoduli
n 
 
3 ml   
 
 
 
Sod Citrate (BLU)  
 
 
 
 
 
 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
 
NIH Clinical Lab 
 
 
 
 
 
Research* 
• 
IL-6 
3mL 
EDTA (lavender) 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
NIH Clinical Lab 
Research* 
• 
Ferritin 
• 
CRP 
4 mL 
Lithium Heparin 
tube (light green) 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
NIH Clinical Lab 
Research (exploratory) 
• 
Serum tube 
8 mL 
Serum Separator 
Red top tube 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
NHLBI Research 
lab (Childs) 


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*Residual bloods from clinical care can be transferred to the NHLBI research lab for storage.  
**TEG (thromboelastography) to be performed at NIH site only. 
***Only one of either RNA collections via Paxgene tubes or cell free DNA collection via Shreck 
tubes will be performed at the discretion of the principal investigator a decision that will be made 
for each individual patient.  
****Day 1 labs should be drawn prior to first study drug administration.  
***** SARS-CoV-2 testing done for research purposes. This test will not be used for diagnostic 
purposes.. 
In addition to the research blood requested above, we will request residual blood from clinical 
labs for research purposes, as available for research purposes. 
8.2.3 Correlative Studies for Research Studies 
As an exploratory endpoint, we will study the immune mechanism by which fostamatinib 
improves outcomes in patients with COVID-19. 
1. Characterization of plasma biomarkers of immune activation 
2. Measure platelet-leukocyte aggregates 
Research (exploratory) 
• 
Plasma  
 
 
• 
PBMC 
 
2 mL 
 
 
9 ml 
 
Sod Citrate (BLU) 
 
 
Sodium Heparin 
Green top 
 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
 
NHLBI Research 
lab (Childs) 
Research (exploratory) 
• 
TEG** 
 
3mL 
 
Sodium Citrate  
 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
 
NIH Site and 
Clinical Lab only 
 
Research (exploratory) 
• 
RNA*** 
 
5mL 
 
Paxgene 
 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
 
NHLBI Research 
lab (Childs) 
Research (exploratory) 
• 
Cell free DNA*** 
5mL 
Shreck tube 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
NHLBI Research 
Lab (Agbor-
Enoh) 
Research (exploratory) 
• 
SARS-CoV-2 
test***** 
OP swab 
Oropharyngeal 
swab 
D1, 3, 5, 8, 11, 
15, 22, 29, 60 
 
NIH Clinical 
Center Lab 


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3. Measure leukocyte activation assays 
4. Measure plasma cytokine and chemokine levels 
5. Evaluate the coagulation cascade 
6. Measurement of immune antigen-antibody complexes  
7. Measurement of thromboelastography (TEG) 
8. Measure biomarkers of endothelial dysfunction 
9. Characterize leukocyte extracellular traps 
10. SARS-CoV-2 viability via cell culture from oropharyngeal samples 
11. Detection of viral antigen blood and oropharyngeal samples  
8.2.4 Samples for Genetic/Genomic Analysis 
There are no genetic/genomic analyses planned on any of the samples. If a decision is 
made to perform DNA or RNA sequencing on any of the samples, the protocol will be 
amended with a GDSP and ICF updated to reflect this. 
8.2.4.1 Description of how privacy and confidentiality of medical information/biological 
specimens will be maximized 
N/A 
8.2.4.2 Management of Results 
N/A 
8.2.4.3 Genetic counseling 
N/A 
8.3 
 SAFETY AND OTHER ASSESSMENTS 
Physical examination A targeted physical examination will be performed at baseline prior to 
initial study product administration on Day 1. The baseline physical examination can be one that 
is conducted from screening to Day 1. Post-baseline physical examinations will be done only 
when needed to evaluate possible adverse event(s) (i.e. any new signs or symptoms). No routine 
physical exam is needed for study visits after Day 1. Targeted physical exam constitutes 
assessment of vital signs, neurological, cardiac, and pulmonary exam. 
Vital signs:  
Vital signs will be done daily and include temperature, systolic blood pressure, heart rate, 
respiratory rate, and O2 saturation. 
Radiographic or other imaging assessments:  
Chest x-ray will be done on enrollment. 
Assessment of adverse events: 
Assessment of adverse events will be performed daily by the study team and as clinically 
indicated. Adverse events that have not resolved after completion of study drug administration 
will be followed until day 60. 
Subjects with LFTS above 3x the ULN at enrollment will have LFTs checked daily during the 
hosplitalization phase of the study.  


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Subjects who are discharged on study drug will receive a daily phone call until day 15 to assess 
for adverse events and will have safety labs drawn as per the schedule safety labs schedule on 
days 3, 5, 8, 11, and 15 as applicable.  
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS.   
8.4.1 Definition of Adverse Event 
An advers event (AE) is any untoward medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or 
disease, temporally associated with the subject’s participation in research, whether or not 
considered related to the subject’s participation in the research. In the context of FDA-required 
reporting, an AE means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related 
 (21 CFR 312.32 (a)). 
8.4.2 Definition of Serious Adverse Events (SAE) 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of 
either the investigator or sponsor, it results in any of the following outcomes: death, a life-
threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or a congenital anomaly/birth defect. Important medical events that may not result in 
death, be life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse. 
8.4.3 Classification of an Adverse Event 
8.4.3.1 Severity of Event 
This study will utilize the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 
v5.0) for toxicity and adverse event reporting.  A copy of the CTCAE v5.0 can be downloaded 
from the https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
AEs will be recorded, verified, and followed until satisfactory resolution (return to baseline or, if 
event was not present prior to study drug initiation, grade 1 or lower).   
Severity definitions found in the CTCAE v5.0 will be used for grading the severity (intensity) of 
AEs: 
1) Mild (Grade 1):  Asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
2) Moderate (Grade 2):  Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL* 


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3) Severe (Grade 3):  Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**. 
4) Life- threatening (Grade 4):  Life-threatening consequences; urgent intervention 
indicated. 
5) Death (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. 
 
8.4.3.2 Relationship to Study Intervention 
All adverse events (AEs) must have their relationship to study intervention assessed by the 
investigator or designee who examines and evaluates the participant based on temporal 
relationship and his/her clinical judgment. The degree of certainty about causality will be graded 
using the categories below. In a clinical trial, the study product must always be suspect.  
• Definitely Related – There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs in a plausible time relationship to study intervention 
administration and cannot be explained by concurrent disease or other drugs or 
chemicals. The response to withdrawal of the study intervention (dechallenge) should be 
clinically plausible. The event must be pharmacologically or phenomenologically 
definitive, with use of a satisfactory rechallenge procedure if necessary. 
• Probably Related – There is evidence to suggest a causal relationship, and the influence 
of other factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time after administration of the study intervention, is 
unlikely to be attributed to concurrent disease or other drugs or chemicals, and follows a 
clinically reasonable response on withdrawal (dechallenge). Rechallenge information is 
not required to fulfill this definition. 
• Possibly Related – There is some evidence to suggest a causal relationship (e.g., the 
event occurred within a reasonable time after administration of the trial medication). 
However, other factors may have contributed to the event (e.g., the participant’s clinical 
condition, other concomitant events). Although an AE may rate only as “possibly related” 
soon after discovery, it can be flagged as requiring more information and later be 
upgraded to “probably related” or “definitely related”, as appropriate. 
• Unlikely to be related – A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study intervention administration makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time after 
administration of the study intervention) and in which other drugs or chemicals or 


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underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments). 
• Not Related – The AE is completely independent of study intervention administration, 
and/or evidence exists that the event is definitely related to another etiology. There must 
be an alternative, definitive etiology documented by the clinician.] 
 
8.4.3.3 Expectedness  
The site principal investigator will be responsible for determining whether an adverse event (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 risk information previously described for the 
study intervention in the package insert or investigator’s brochure. 
8.4.4 Time Period and Frequency for Event Assessment and Follow-Up 
For this study, all grade 3 and 4 AE, clinically significant laboratory abnormalities, and all SAEs 
occurring from the time the informed consent is signed through the Day 60 visit will be 
documented, recorded, and reported in an NHLBI-approved research database. All other AEs 
will be collected in the subject’s medical records. 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a study participant presenting for medical care, or upon review by a 
study monitor. 
All reportable AEs including local and systemic reactions not meeting the criteria for SAEs will 
be captured on the appropriate CRF. Information to be collected includes event description, time 
of onset, clinician’s assessment of severity, relationship to study product (assessed only by those 
with the training and authority to make a diagnosis), and time of resolution/stabilization of the 
event. All AEs occurring while on study must be documented appropriately regardless of 
relationship. All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened and until 
participant receives the first dose of study drug will be considered as baseline and not reported as 
an AE. AE occurrence will be assessed as any change from baseline in any medical condition 
that results in worsening in severity and/or frequency of the medical condition, whether or not 
considered related to study medication. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
8.4.5 Adverse Event Reporting  
Information on AEs will be recorded on the appropriate CRF. All clearly related signs, 
symptoms, and results of diagnostic procedures performed because of an AE should be grouped 
together and recorded as a single diagnosis. If the AE is a laboratory abnormality that is part of a 


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clinical condition or syndrome, it should be recorded as the syndrome or diagnosis rather than 
the individual laboratory abnormality. Each AE will also be described in terms of duration (start 
and stop date), severity, association with the study product, action(s) taken, and outcome.  
Disease related events are still being determined as COVID-19 is a new disease however we 
know that COVID-19 can lead to: (Berlin, Gulick & Martinez, 2020) 
• Thromboembolism (Deep venous thrombosis, pulmonary emboli) 
• Cardiac (myocarditis, cardiogenic shock, takotsubo cardiomyopathy) 
• Renal (acute kidney injury, proteinuria) 
• Neurological (ageusia, myalgia, anosmia, stroke, headache) 
• Gastrointestinal (diarrhea, weight loss, anorexia)  
Due to the overlap of expected GI symptoms in subjects receiving fostamatinib, GI symptoms 
are highly likely to have at least a possible attribution to the study drug. 
8.4.6 Serious Adverse Event Reporting  
The study investigator will report any SAE to the Data Coordinating Center (DCC)/study 
sponsor (NHLBI) no later than 72 hrs after the investigator becomes aware of the SAE, whether 
or not considered study-intervention related, including those listed in the protocol or package 
insert and must include an assessment of whether there is a reasonable possibility that the study 
intervention caused the event.  
All SAEs will be followed until satisfactory resolution or until the site investigator deems the 
event to be chronic or the participant is stable. Other supporting documentation of the event may 
be requested by the Data Coordinating Center (DCC)/study sponsor and should be provided as 
soon as possible. 
SAEs from all sites will be reported to the IRB of record (NIH intramural IRB) in accordance 
with the Policy 801. The sites should report SAE locally in accordance with institutional 
requirements. 
IND safety reports will be submitted to FDA by the IND sponsor in accordance with 21 CFR 
312. 
Data Coordinating Center (DCC)/study sponsor (NHLBI) will provide Rigel with copies of all 
IND Safety Reports concurrently with their submission to the FDA. The IND Safety Reports 
should be sent to the following email or fax: 
Email: clinsafety@rigel.com 
Fax: +1.650.745.0971 
The site may contact Rigel Drug Safety at the above fax/e-mail with questions regarding 
reporting of SAEs. 
Reports to the NHLBI Clinical Director 
Data Coordinating Center (DCC)/study sponsor (NHLBI) will refer to NHLBI DIR Policy to 
determine Clinical Director reporting requirements and timelines. 


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Reports to the DSMB 
The NHLBI Lung DSMB as the independent data safety monitoring commitee will review and 
approve the protocol before the enrollment.  SAEs that meet the definition of an Unanticipated 
Problem will be submitted to the DSMB within 7 days of the investigator being notified of the 
event.  DSMB will have access to safety data upon request any time. The monitoring plan will be 
developed and approved by the DSMB before enrollment. Additionally, the DSMB will be 
available for ad hoc reviews for AE/SAE, or safety concerns. The study will not stop enrollment 
awaiting these DSMB reviews, though the DSMB may recommend temporary or permanent 
stopping of enrollment based on their safety reviews.   
 
8.4.7 Events of Special Interest  
N/A 
8.4.8 Reporting of Pregnancy  
Pregnancy is not an AE. However, any pregnancy that occurs during study participation should 
be reported to the Sponsor on the appropriate CRF. Pregnancy should be followed to outcome.  
8.5 
UNANTICIPATED PROBLEMS 
8.5.1 Definition of Unanticipated Problems (UP) 
Any incident, experience, or outcome that meets all of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; and 
• Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• Suggests that the research places participants or others (which many include research 
staff, family members or other individuals not directly participating in the research) at a 
greater risk of harm (including physical, psychological, economic, or social harm) than 
was previously known or expected. 
8.5.2  Unanticipated Problem Reporting  
The investigator will report unanticipated problems (UPs) to the NIH Institutional Review Board 
(IRB) as per Policy 801. 
8.5.3 NIH Intramural IRB Reporting of IND Safety Reports 
Only IND Safety Reports that meet the definition of an unanticipated problem will need to be 
reported to the NIH Intramural IRB. 


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9 
STATISTICAL CONSIDERATIONS 
9.1 
SAMPLE SIZE DETERMINATION 
This study plans to enroll approximately 60 eligible subjects, randomized in a 1:1 ratio to 
fostamatinib or placebo.  
The primary outcome of the study is cumulative incidence of SAEs through day 29.  Because of 
data on safety of the fostamatinib in combination with standard of care is unavailable, the sample 
size is determined by the feasibility to assess the activity and safety of the study treatment in a 
diverse group of hospitalized adults.  As background standards of supportive care may 
evolve/improve over time as more is learned about successful management of COVID-19, 
comparisons of safety will be based on data from concurrently randomized subjects between 
fostamatinib and placebo arm.  Randomization is essential to evaluate the safety and early 
efficacy of fostamatinib, which may lead to generalizable evidence of future confirmative 
studies.   
9.2 
POPULATIONS FOR ANALYSES 
9.2.1 Evaluable for toxicity  
All randomized patients will be evaluated for toxicity from the time of their first treatment with 
study drug.  
9.2.2 Evaluable for primary analysis  
All randomized patients who heave received any study drug or placebo will be included in 
the primary outcome analysis 
9.3 
STATISTICAL ANALYSES 
9.3.1 General Approach 
Descriptive statistics will be used to summarize baseline characteristics and severity of illness.  
For continuous measures, the mean (standard deviation) or median (interquartile range) will be 
presented. For categorical variables, the frequency and the percentage in each category will be 
presented. All randomized patients receiving any study drug or placebo on study will be included 
in the safety analysis.   
9.3.2 Analysis of the Primary Endpoints 
Primary endpoint analysis will include descriptive statistics on the incidence of serious adverse 
events by the study arm.  The difference in the percentages of SAEs between the treatment arms 
will be assessed by Fisher’s exact test. 
9.3.3 Analysis of the Secondary Endpoint(s) 
To determine a subject’s clinical status using the ordinal scale: On Day 1, report their clinical 
status at enrollment (start of study drug). On Day 2, report the period from enrollment to 
midnight on Day 1. On Day 3 through Day 11, or until discharged, and on Days 15, 22 and 29, 
provide the worst clinical assessment for the previous day (i.e., midnight to midnight; 00:00 – 


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23:59 (24-hr clock)). For example, on study Day 3 when completing the form, the worse clinical 
outcome measure of Day 2 is captured with the worst being death followed by ECMO, 
mechanical ventilation, etc. The Day 2 measurement is assessed as occurring anytime in that 24-
hour period (00:00 to 23:59).  
Secondary endpoints will be evaluated as follows: 
1) The time to recovery by Day 29,  it will be estimated by median and 95% confidence interval 
by study arm. The cumulative recovery rate will be estimated by the Kaplan-Meier method.  The 
comparison between two treatment arms will be assessed by the log-rank test. The recovery ratio 
and hazard ratios will be based on the Cox model.  The analysis will be stratified by disease 
severity at enrollment. 
The time to recovery will be evaluate and censored up until Day 29.  It is defined as the elapsed 
time in days from the day 1 to the earliest day at which a subject reaches recovery (having 1-3 of 
the 8-point ordinal scale).  Any subjects that are lost to follow-up prior to an observed recovery 
will be censored at the day of their last observed assessment. Subjects who complete follow-up 
but do not experience recovery will be censored at Day 29.  All deaths within Day 29 (and prior 
to recovery) will be considered censored at Day 29.  Analysis will be based on intention to treat 
including all randomized patients. Patients who have received at least four doses of study drug 
will be considered  in a sensitivity analysis for this secondary outcome.  
2) Duration of events (e.g., mechanical ventilation or days in the ICU) will be summarized with 
median and interquartile rage by the study arms and compared between the treatment arms by 
Wilcoxon’s rank sum test or log-rank test.  
3) Binary events (e.g., need for intubation) will be summarized as percentages and 95% 
confidence intervals by the study arms and compared between the treatment arms by Fisher’s 
exact test. 
4) Mortality rate and the time to event endpoints will be estimated by Kaplan-Meier method and 
95% confidence intervals by study arm and compared between the treatment arms by log-rank 
test. 
5) Longitudinal measurements of each biomarker variables will be plotted over time. The mean 
and percent change from baseline for each variable will be estimated and compared to study arm 
using appropriate parametric or nonparametric tests and regression modeling.  
9.3.4 Safety Analyses 
The planned analyses will also include descriptive statistics on the incidence and severity of 
adverse events.  The proportions of serious adverse events (SAEs) will be summarized using 
sample proportions and confidence intervals for binomial distributions.  Safety will be 
summarized using descriptive statistics to assess the difference between the two study arms. 
Summaries will be produced for all adverse events (AEs), related AEs (those considered by the 
Investigator as related to study treatment), SAEs, AEs leading to treatment discontinuation, and 
AEs Grade ≥3 in severity. Individual subject listings will be provided for any deaths, SAEs, AEs 
leading to interruption and AEs leading to treatment discontinuation for the fostamatinib arm 
compared to the placebo arm.  


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9.3.5 Baseline Descriptive Statistics 
Baseline characteristics will be summarized by treatment arm. For continuous measures the 
mean and standard deviation will be summarized. Categorical variables will be described by the 
proportion in each category (with the corresponding sample size numbers).  
9.3.6 Planned Interim Analyses 
Interim safety analysis will be performed as requested by the by the NHLBI appointed, 
independent DSMB. Stopping guidelines will be evaluated if excess deaths or SAEs occur in the 
fostamatinib arm compared to the placebo arm. The number of interim montoring looks and the 
stopping boundary based on the differences in the mortality rate and SAE between the two study 
arms will be developed and approved by the DSMB before the study enrollment.  DCC will 
monitor the stopping boundary to alert DSMB if the stopping boundary is reached and have 
DSMB make further evaluation and recommendation about stopping the study due to safety 
reasons. 
 
9.3.7 Sub-Group Analyses 
The following subgroups analysis will be performed. 
• Symptoms duration >10 and ≤10 days 
• Baseline disease severity 
• Race (White, Black, Asian) 
• Age (18 to <40, 40 to <66, ≥65) 
• Sex (male and female) 
• Concomitant therapies (e.g. treatment with and without remedesivir, steroids 
(dexamethasone, prednisone, hydrocortisone, methylprednisolone), convalescent plasma, 
tocilizumab or other immunomodulators intended for the treatment of COVID-19 
• Therapy with anti-coagulation by dose 
9.3.8 Tabulation of individual Participant Data 
Individual participant data may be listed by severity, measures received and time points in future 
study communications or publications.  
9.3.9 Exploratory Analyses 
Exploratory correlative analysis will be performed to study the longitudinal changes of 
biomarkers with time to recovery and treatment response, and the immune mechanism by which 
fostamatinib improves outcomes in patients with COVID-19.   
10 REGULATORY AND OPERATIONAL CONSIDERATIONS 
10.1 INFORMED CONSENT PROCESS 
10.1.1 Consent Procedures and Documentation 
Informed consent shall be documented using the current IRB-approved consent form. The 
investigational nature and objectives of this trial, the procedures and treatments involved, and 


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their attendant risks and discomforts and potential benefits will be carefully explained in person 
to the patient, and a signed informed consent document will be obtained by the PI or any person 
authorized to consent. 
When consent is obtained, the consent document(s) must be signed and dated by the subject, and 
the person obtaining consent. Telephone or any institution-approved electronic consent process 
can be used.The original, signed informed consent document will be placed in the medical 
record, and the subject will receive a signed copy of the informed consent document. 
Documentation of informed consent and the signed consent form will be maintained per 
institution requirements. 
10.1.2 Participation of Subjects who are/become Decisionally Impaired 
Subjects unable to consent due to complications from COVID may be enrolled in this study at 
participating/enrolling sites. The process for determining capacity and obtaining legally effective 
consent will be determined by applicable regulations and local policies. At the NIH the PI or AI 
will contact the NIH Ability to Consent Assessment Team (ACAT) for evaluation as needed for 
the following: an independent assessment of whether an individual has the capacity to provide 
consent; assistance in identifying and assessing an appropriate surrogate when indicated; and/or 
an assessment of the capacity to appoint a surrogate. For those subjects that become 
incapacitated and do not have pre-determined substitute decision maker, the procedures 
described in NIH HRPP SOP 14E for appointing a surrogate decision maker for adult subjects 
who are (a) decisionally impaired, and (b) who do not have a legal guardian or durable power of 
attorney, will be followed. 
 
10.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigator, the Investigational New Drug (IND) sponsor and regulatory authorities.  If the study 
is prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform 
study participants, the Institutional Review Board (IRB), and sponsor and will provide the 
reason(s) for the termination or suspension.  Study participants will be contacted, as applicable, 
and be informed of changes to study visit schedule. 
 Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Data that are not sufficiently complete and/or evaluable 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
10.3 CONFIDENTIALITY AND PRIVACY 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 


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participants. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical 
records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor requirements. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the NHLBI OCD. This will not include the 
participant’s contact or identifying information. Rather, individual participants and their research 
data will be identified by a unique study identification number. The study data entry and study 
management systems used by clinical sites will be secured and password protected. At the end of 
the study, all study databases will be de-identified and archived at the NHLBI OCD. 
To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve 
the research objectives and promote participation in studies by helping assure confidentiality and 
privacy to participants. 
10.4 FUTURE USE OF STORED SPECIMENS AND DATA 
We may share specimens and data with other researchers for future use. 
Following analyses of biospecimens for primary research purposes as described in the protocol, 
remaining samples suitable for future research will be stored in manner that conforms with DIR 
policy (such as BSI) or in a publicly accessible research biospecimen repository following IRB 
approval.  Biospecimens may be destroyed only when permitted by the clinical director and 
approved by the IRB.  Any future research use of identifiable biospecimens not defined in the 
research protocol will occur only after IRB review and approval. 
10.5 SAFETY OVERSIGHT 
Safety oversight will be under the direction of a Data and Safety Monitoring Board (DSMB) 
composed of individuals with the appropriate expertise, including pulmonary and critical care 
medicine. Members of the DSMB should be independent from the study conduct and free of 
conflict of interest, or measures should be in place to minimize perceived conflict of interest.  


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The monitoring plan for interim safety and efficacy data will be developed and approved by 
DSMB before study enrollment. The unblinded statistical team will prepare these closed reports 
for DSMB review and recommendations. Analyses will be presented with blinded codes for 
treatment arms to protect against the possibility that the DSMB report may fall into the wrong 
hands. If there is a pattern of unexpected AEs and safety concerns, the DSMB will be asked to 
review unblinded safety data in an ad hoc meeting.  The DMSB will operate under the rules of an 
approved charter that will be written and reviewed at the organizational meeting of the DSMB. 
At this time, each data element that the DSMB needs to assess will be clearly defined. The 
DSMB will provide its input and recommendations to Dr. Richard Childs, who is the sponsor’s 
authorized representative for the NHLBI Office of the Clinical Director 
10.6 CLINICAL MONITORING 
As per ICH-GCP 5.18 and FDA 21 CFR 312.5 clinical protocols are required to be adequately 
monitored by the study sponsor. The monitoring of this study will be conducted by Clinical  
Research Associates (CRAs)/Monitors employed by an independent contract organization 
working under an agreement with NHLBI to monitor aspects of the study in accordance with the 
appropriate regulations and the approved protocol. The objectives of a monitoring visit will be: 1) 
to verify the existence of signed informed consent form (ICF) and documentation of the ICF 
process for each monitored subject; 2) to verify the prompt and accurate recording of all monitored 
data points, and prompt reporting of all SAEs; UPs, and deviations, 3) to compare abstracted 
information with individual subjects’ records and source documents (subject’s charts, laboratory 
analyses and test results, physicians’ progress notes, nurses’ notes, and any other relevant original 
subject information); and 4) to help ensure investigators are in compliance with the protocol and 
with the appropriate regulations. The monitors also will inspect the clinical site regulatory files to 
ensure that regulatory requirements (Office for Human Research Protections-OHRP) and 
applicable guidelines (ICH-GCP) are being followed.  During the monitoring visits, the 
investigator (and/or designee) and other study personnel will be available to discuss the study 
progress and monitoring visit. 
The investigator (and/or designee) will make study documents (e.g., consent forms and pertinent 
hospital or clinical records) readily available for inspection by the local IRB, the site monitors, and 
the NHLBI staff for confirmation of the study data. 
10.7 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  An individualized quality management 
plan will be developed to describe a site’s quality management. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted and data are generated and biological specimens are collected, 
documented (recorded), and reported in compliance with the protocol, International Conference 
on Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements 
(e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)).  


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The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. 
 
10.8 DATA HANDLING AND RECORD KEEPING 
10.8.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.   
Hardcopies of the study visit worksheets will be provided for use as source document worksheets 
for recording data for each participant enrolled in the study.  Data recorded in the electronic case 
report form (eCRF) derived from source documents should be consistent with the data recorded 
on the source documents.  
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into <specify name of data capture 
system>, a 21 CFR Part 11-compliant data capture system provided by the <specify Data 
Coordinating Center>. The data system includes password protection and internal quality checks, 
such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
10.8.2 Study Records Retention 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an International Conference on Harmonisation (ICH) region and until 
there are no pending or contemplated marketing applications in an ICH region or until at least 2 
years have elapsed since the formal discontinuation of clinical development of the study 
intervention, or as per the NIH Intramural Records Retention Schedule. No records will be 
destroyed without the written consent of the sponsor. It is the responsibility of the sponsor to 
inform the investigator when these documents no longer need to be retained. 
 
10.9 PROTOCOL DEVIATIONS 
It is the responsibility of the investigator to use continuous vigilance to identify and report 
deviations to the NIH Institutional Review Board as per Policy 801.  All deviations must be 
addressed in study source documents, reported to Dr. Jeffrey Strich, and Dr. Richard Childs, 
Sponsor’s authorized representative. The investigator is responsible for knowing and adhering to 
the reviewing IRB requirements. 
10.9.1 NIH Definition of Protocol Deviation 
A protocol deviation is any changed, divergence, or departure from the IRB-approved research 
protocol.  


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• Major deviations: Deviations from the IRB approved protocol that have, or may have the 
potential to, negatively impact the rights, welfare or safety of the subject, or to 
substantially negatively impact the scientific integrity or validity of the study. 
• Minor deviations: Deviations that do not have the potential to negatively impact the 
rights, safety or welfare of subjects or others, or the scientific integrity or validity of the 
study. 
10.10 PUBLICATION AND DATA SHARING POLICY 
10.10.1Human Data Sharing Plan 
This study will be conducted in accordance with the following publication and data sharing 
policies and regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of 
NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results 
Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and 
results information from this trial will be submitted to ClinicalTrials.gov. In addition, every 
attempt will be made to publish results in peer-reviewed journals.  Data from this study may be 
requested from other researchers after the completion of the primary endpoint by contacting Dr. 
Richard Childs, who is the accountable investigator. 
10.10.2Genomic Data Sharing Plan 
N/A 
10.11 COLLABORATIVE AGREEMENTS  
10.11.1Agreement Type 
A Clinical Research and Development Agreement (CRADA) between NHLBI and Rigel 
Pharmaceutics for the conduct of this study is being executed. 
Transfers that are associated with correlative studies conducted under an approved 
protocol: Investigators in the NIH intramural program will participate in this multi-site clinical 
trials the coordinating center. Human materials will be transferred from external sites to the 
intramural program for correlative studies that are part of the approved protocol. The tests 
conducted under the correlative studies, and each institution participating in the clinical study are 
bound by the terms of their Protocol and their obligations under the statutes and regulations.  
 
10.12 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 


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required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial.  The study leadership in conjunction with NHLBI has 
established policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported dualities of interest. 
 
11 ABBREVIATIONS 
 
ACTT 
Adaptive COVID Treatment Trials 
AE 
Adverse Event 
ARDS 
Acute respiratory distress syndrome 
CFR 
Code of Federal Regulations 
CONSORT 
Consolidated Standards of Reporting Trials 
CRADA 
Clinical Research and Development Agreement 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DSMB 
Data Safety Monitoring Board 
DVT 
Deep Vein Thrombosis 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
NETs 
Neutrophil Extracellular Traps 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
NHLBI 
National Heart, Lung, and Blood Institute 
OCD 
Office of the Clinical Director 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
PRO 
Patient Recruitment Office 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus-2 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
SYK 
Spleen Tyrosine Kinase 
UP 
Unanticipated Problem 


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US 
United States 
 
12 REFERENCES  
Al-Harbi, N., Nadeem, A., Ahmad, S., Alanazi, M., Aldossari, A., & Alasmari, F. (2019). 
Amelioration of sepsis-induced acute kidney injury through inhibition of inflammatory 
cytokines and oxidative stress in dendritic cells and neutrophils respectively in mice: Role of 
spleen tyrosine kinase signaling. Biochimie, 158, 102-110. doi: 10.1016/j.biochi.2018.12.014 
 
Alimova M. et al. A High Content Screen for Mucin-1-Reducing Compounds Identifies 
Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the 
COVID-19 pandemic (2020). Retrieved 22 July 2020, from 
https://www.biorxiv.org/content/10.1101/2020.06.30.180380v1.full.pdf 
 
Beigel, J., Tomashek, K., Dodd, L., Mehta, A., Zingman, B., Kalil, A., et al. (2020). 
Remdesivir for the Treatment of Covid-19 — Preliminary Report. New England Journal Of 
Medicine. doi: 10.1056/nejmc2022236 
 
Berlin, D., Gulick, R., & Martinez, F. (2020). Severe Covid-19. New England Journal Of 
Medicine. doi: 10.1056/nejmcp2009575 
 
Fostamatinib FDA label (2020). Retrieved 22 July 2020, from 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209299lbl.pdf 
 
Hoepel, W., Chen, H., Allahverdiyeva, S., Manz, X., Aman, J., & Bonta, P. et al. (2020). 
Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-
inflammatory responses. Retrieved 22 July 2020, from 
https://www.biorxiv.org/content/10.1101/2020.07.13.190140v1  
 
Nadeem, A., Ahmad, S., Al-Harbi, N., Al-Harbi, M., Ibrahim, K., & Kundu, S. et al. (2019). 
Inhibition of spleen tyrosine kinase signaling protects against acute lung injury through 
blockade of NADPH oxidase and IL-17A in neutrophils and γδ T cells respectively in 
mice. International Immunopharmacology, 68, 39-47. doi: 10.1016/j.intimp.2018.12.062 
 
Rapkiewicz, A., Mai, X., Carsons, S., Pittaluga, S., Kleiner, D., & Berger, J. et al. (2020). 
Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy 
in COVID-19: A case series. Eclinicalmedicine, 100434. doi: 10.1016/j.eclinm.2020.100434 
 


Abbreviated Title: Fostamatinib for COVID 
Version Date: 09/17/2020 
 
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The RECOVERY Collaborative Group (2020). Dexamethasone in Hospitalized Patients with 
Covid-19 — Preliminary Report. New England Journal Of Medicine. doi: 
10.1056/nejmoa2021436 
 
Weinblatt, M., Kavanaugh, A., Burgos-Vargas, R., Dikranian, A., Medrano-Ramirez, G., & 
Morales-Torres, J. et al. (2008). Treatment of rheumatoid arthritis with a syk kinase inhibitor: 
A twelve-week, randomized, placebo-controlled trial. Arthritis & Rheumatism, 58(11), 3309-
3318. doi: 10.1002/art.23992 
 
World Health Organization 2020.  WHO R&D Blueprint,  novel Coronavirus COVID-19 
Therapeutic Trial Synopsis.  Retrieved August 27, 2020, from 
https://www.who.int/publications/i/item/covid-19-therapeutic-trial-synopsis 
 
Zhao, X., Chu, H., Wong, B., Chiu, M., Wang, D., & Li, C. et al. (2019). Activation of C-
Type Lectin Receptor and (RIG)-I-Like Receptors Contributes to Proinflammatory Response 
in Middle East Respiratory Syndrome Coronavirus-Infected Macrophages. The Journal Of 
Infectious Diseases. doi: 10.1093/infdis/jiz483 

ICF_000.pdf: 
 
 
 
Title: A Phase II Study Evaluating Fostamatinib for Hospitalized Adults with COVID-19  
NCT: 04579393 
Document Date: 02/05/2021 


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
Page 1 of 13
CC ICF template v. 05.05.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR:  Jeffrey R. Strich, MD
STUDY TITLE: A Phase II Study Evaluating Fostamatinib for Hospitalized Adults with COVID-
19
STUDY SITE: NIH Clinical Center
Cohort: Affected patient
Consent Version:  02/05/2021
WHO DO YOU CONTACT ABOUT THIS STUDY? 
Jeffrey Strich, MD: strichj@niaid.nih.gov; 301-496-9320 
Jennifer Kyte, RN, DNP, ACNS-BC: jennifer.kyte@nih.gov; 301-827-0367
KEY INFORMATION ABOUT THIS RESEARCH 
This consent form describes a research study and is designed to help you decide if you would 
like to be a part of the research study.  
You are being asked to take part in a research study at the National Institutes of Health (NIH). 
This section provides the information we believe is most helpful and important to you in making 
your decision about participating in this study. Additional information that may help you decide 
can be found in other sections of the document. Taking part in research at the NIH is your choice.
The purpose of this research study is to find out whether a drug called fostamatinib is safe for 
patients seriously ill with COVID-19, and if this drug can improve the patients’ health. 
Fostamatinib has not been approved to treat COVID-19. However, the use of fostamatinib is 
approved to treat immune thrombocytopenia (bleeding disorder). We are testing it in this 
research study to see if fostamatinib can improve patients’ health when they are seriously sick 
with COVID-19.
While in a hospital, you will be treated for COVID-19 in accordance with the current medical 
standard of care. Your doctors will decide what the best treatment options for you are. Joining 
this study will not affect your standard COVID-19 treatment. 
If you decide to take part in this study, in addition to your standard COVID-19 treatment you 
will be taking either fostamatinib pills or placebo (“dummy” pills). Also, as part of this study, 
you will undergo frequent blood tests to check your health and how your body responds to the 
research treatment.  Your involvement is expected to last for about two months.
Known side effects of fostamatinib include diarrhea, high blood pressure, nausea, respiratory 
infection, dizziness, increased liver enzymes, rash, abdominal pain, fatigue, chest pain, and low 
blood counts.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
Page 2 of 13
CC ICF template v. 05.05.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
The remaining document will now describe the research study in more detail.  This information 
should be considered before you make your choice. Members of the study team will talk with you 
about the information in this document. Some people have personal, religious, or ethical beliefs 
that may limit the kinds of medical or research treatments they would want to receive (such as 
blood transfusions). Take the time you need to ask any questions and discuss this study with NIH 
staff, and with your family, friends, and personal health care providers.
If the individual being asked to participate in this research study is not able to give consent for 
themselves, you, as the Legally Authorized Representative, will be their decision-maker and you 
are being asked to give permission for this person to be in this study. For the remainder of this 
document, the term “you” refers to you as the decision-maker and/or the individual being asked to 
participate in this research. 
IT IS YOUR CHOICE TO TAKE PART IN THE STUDY
You may choose not to take part in this study for any reason. If you join this study, you may change 
your mind and stop participating in the study at any time and for any reason. In either case, you 
will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you 
must be taking part in a study or are being considered for a study. If you do choose to leave the 
study, please inform your study team to ensure a safe withdrawal from the research.  
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to find out whether a drug called fostamatinib is safe and if 
it can improve patients’ health when they are seriously ill with COVID-19.
COVID-19 is a new disease caused by a virus that was just identified in 2019. Some people who 
become sick with COVID-19 become seriously ill and must be hospitalized. There are some 
medicines that may assist patient’s recovery. There are no medicines that cure the disease. Some 
hospitalized patients die even after all treatment options have been given.
Early data suggest that a drug called fostamatinib may help patients with COVID-19. This study 
will test fostamatinib in adults that are hospitalized with COVID-19. 
We want to compare the effect of giving fostamatinib pills with placebo pills. The placebo “dummy” 
pill looks like the real drug but does not have the drug in it. Using a placebo is common in research 
studies. 
We are asking you to join this research study because you have been diagnosed with COVID-19 
and are currently hospitalized.
Fostamatinib is considered investigational, which means that it has not been approved by the U.S. 
Food and Drug Administration (FDA) to treat COVID-19. However, the use of fostamatinib is 
approved to treat immune thrombocytopenia (bleeding disorder). We are testing it in this research 
study to see if fostamatinib can improve patients’ health when they are seriously sick with COVID-
19.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
Page 3 of 13
CC ICF template v. 05.05.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
WHAT WILL HAPPEN DURING THE STUDY?
While in a hospital, you will be treated for COVID-19 in accordance with the current medical 
standard of care. Your doctors will decide what are the best treatment options for you. Joining this 
study will not affect your standard COVID-19 treatment. 
Before you begin the study 
If you decide to take part in this study, you will be asked to do some tests to make sure it is safe 
for you to join. 
•
Physical examination, including weight and vital signs
•
Blood test to evaluate your liver, kidney and immune system 
•
COVID-19 test (if not taken already within 7 days) will be performed as an oropharyngeal 
swab (swab of the back of your throat) or a nasopharyngeal swab (swab of the back of your 
nose) 
•
Pregnancy test (if you are a woman who can have children)
•
Chest X-Ray will be done to check the condition of your lungs
During the study
Study drug: 
If you join the study, you will be randomly put into one of two groups. This is decided by chance, 
similar to flipping a coin. Out of every 2 people on this study, 1 will get fostamatinib, and 1 will 
get placebo. You will have an equal chance of being in either of the study groups. You and the 
study staff will not know what group you are in. When the study is over, we will learn if 
fostamatinib is safe and more successful in treating people with COVID-19 than standard of care 
alone. 
After all participants have completed the study, we will contact you to tell you whether you got 
fostamatinib or the placebo.
You will get fostamatinib pills or placebo pills for 14 days. 
•
If you get fostamatinib, the dose will be 150 mg twice daily The placebo pills will look like 
the study drug but do not have the drug in it.  If you able to swallow, the pills will be taken by 
mouth with water. If you are unable to swallow or on mechanical ventilation, the pills will be 
crushed, mixed with water and given to you through a orogastric (OG) or nasogastric (NG) 
tube that carries medicine to the stomach through the mouth or nose. Your doctor or nurse will 
insert a thin plastic tube through your nostril, or your mouth down your esophagus, and into 
your stomach. Once this tube is in place, they can use it to give you medicine.
•
If you recover and are discharged prior to day 14, you will be given the pills to take home with 
you, and to continue taking them up until day 14. 
•
If at any time your doctor determines that it is no longer safe for you to take the study drug, 
the drug will be discontinued. If this happens, you will still need to complete blood tests and 
follow-up visits described below.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
Page 4 of 13
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Blood Tests: While you are in a hospital, we will be taking samples of your blood for health tests  
on approximately days 1, 3, 5, 8, 11, 15, 22, 29, and 60, unless you are discharged earlier than that. 
Blood tests may be done more frequently, as often as once daily if initial blood work shows some 
abnormalities.
Additionally, on those days we will be taking about 3 tablespoons of your blood for research 
purposes, to check how your body responds to the treatment. Once you are discharged from the 
hospital, we will draw your blood during follow-up visits as described below.
Follow Up Visits: After your discharge , you will be asked to return to Clinical Center for a 
safety follow up visits on approximately days 5, 8, 11, 15, 22, 29, and 60. At these visits you will 
get blood draws for health checks and research tests, your vital signs will be taken, and you will 
be asked questions about your health.  If you are unable to visit the Clinical Center, the doctor 
will speak to you on the phone, or will arrange a telehealth visit, or outside lab visit. If you are 
still hospitalized on those days, these checks will be done by the study group at the hospital.
COVID-19 swab test will be done on approximately days 1, 3, 5, 8, 11, 15, 22, 29, and 60 during 
your participation in the study to study how the virus is cleared by the body.
What you should avoid during your participation in this study
•
While participating in this study you should refrain from drinking alcohol.
•
If you are a woman who can have children, once discharged, you should avoid pregnancy 
through abstinence or use of at least one contraceptive until 30 days after last day of study 
drug.
HOW LONG WILL THE STUDY TAKE?
If you agree to take part in this study, your involvement is expected to last for about  60 days. It 
will include your time in the hospital and follow up visits to the Clinical Center. Visits usually take 
about 1 hour, but may be longer.
HOW MANY PEOPLE WILL PARTICIPATE IN THIS STUDY?
We plan to have approximately 10 people participate in this study at the NIH. 
Up to 80 people might also participate at other study sites.
WHAT ARE THE RISKS AND DISCOMFORTS OF BEING IN THE STUDY?
Blood draws
We will insert a new, clean needle into a vein in your arm to take blood. You may feel a pinch 
when the needle goes through your skin. A bruise may appear where it was put in. You may also 
have swelling, and the area may be sore. These things are common and should go away in a couple 
of days. If you already have a central line in place, we will draw the blood from that line. 
Orogastric (OG) or nasogastric (NG) tube insertion
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
If your NG tube isn’t inserted properly, it can potentially injure the tissue inside your nose, sinuses, 
throat, esophagus, or stomach. This is why placement of the NG tube is checked and confirmed to 
be in the correct location before any other action is performed.
Chest X-Ray
If you haven’t had a chest X-ray, while hospitalized, we will ask for one. Chest X-ray is a quick 
and painless procedure that involves standing or lying on your back in front of X-ray machine. 
There are no discomforts associated with X-ray scan.
COVID swab test
The test has few risks. You may gag a little during the test. You may also feel slightly 
uncomfortable, but you shouldn’t feel any pain. You may have a minor nosebleed afterwards.
Placebo Pills
There are no risks of taking placebo pills, but you will not know if you are taking placebo pills or 
the study drug.
Potential Risks of Fostamatinib 
Based on the studies conducted to date with fostamatinib, the following side effects are 
considered possibly related to the use of fostamatinib:
•
Very Common; may affect more than 1 in 10 people
o
Diarrhea (includes frequent bowel movement)
o
High or increased blood pressures (hypertension) 
o
Shortness of breath, tightening in the chest, difficulty breathing
o
Nausea
o
Dizziness
o
High levels of certain liver blood tests (increased liver enzymes, increased alanine 
aminotransferase or increased aspartate aminotransferase)
•
Common; may affect up to 1 in 10 people
o
Red and/or bumpy rash 
o
Upper and lower respiratory tract infection
o
Chest pain not caused by heart disease
o
Fatigue 
o
Decreased number of white blood cells that fight infection (neutropenia)
o
Abdominal pain (includes upper abdominal pain)
o
Abnormal taste
o
An inflammation of lining in the tubes carrying air to your lungs (bronchitis)
These side effects usually go away when the drug is stopped.
If you are experiencing significant diarrhea, or stomach or abdominal pain, please tell your study 
doctor.  Your study doctor may provide you with medications to ease these symptoms and allow 
you to continue to participate in this study.
There is a possibility of allergic reaction to fostamatinib, like rash, hives, itching with or without 
fever, tightness in the chest or throat, wheezing, trouble breathing or talking, unusual hoarseness, 
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Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
or swelling of the lips, mouth, face, throat, or tongue. Contact the study doctor immediately, if you 
should experience any of these symptoms.
What are the risks related to pregnancy? 
If you are able to become pregnant, we will ask you to have a pregnancy test before starting this 
study. You must use effective birth control methods and try not to become pregnant while 
participating in this study. If you become pregnant, there may be unknown risks to the fetus or 
unborn child, or risks that we did not anticipate. There may be long-term effects of the treatment 
being studied that could increase the risk of harm to a fetus. You must tell the study doctor if your 
birth control method fails while you are in the study. If you think or know you have become 
pregnant while participating in this research study, please contact the study team as soon as 
possible. If you plan to become pregnant in the future, please discuss with the study team how long 
you need to wait before becoming pregnant after completing the study.
If you are a sexually active person with a partner able to become pregnant, it is important that your 
partner not become pregnant during your participation in this study. There may be unknown risks 
to a fetus or risks we did not anticipate. You and your partner must agree to use birth control if 
you want to take part in this study. If you think your partner has become pregnant during your 
participation in this study, please contact the study team as soon as possible.  If you and your 
partner plan for your partner to become pregnant after your participation in this study, please 
discuss this with the study team.
What are the risks of radiation from being in the study? 
You may not participate in this study if you are pregnant. If you are able to become pregnant, we 
will perform a pregnancy test before exposing you to radiation. You must tell us if you may have 
become pregnant within the previous 14 days because the pregnancy test is unreliable during that 
time.
During your participation in this research study, you will be exposed to radiation from one chest 
X-ray.  This is considered a low exposure. The risk of this exposure is too low to be reliably 
measured. 
Every day, people are exposed to low levels of radiation that come from the sun and the 
environment around them.  This type of radiation is called “background radiation”.   No one knows 
for sure whether exposure to these low amounts of radiation is harmful to your body.  The radiation 
you will get by participating in this study is less than the average yearly background radiation in 
the United States.
WHAT ARE THE BENEFITS OF BEING IN THE STUDY?
You might not benefit from being in this study. 
Are there any potential benefits to others that might result from the study?
In the future, other people might benefit from this study because what we learn in this study may 
eventually be used to treat others with COVID-19.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
WHAT OTHER OPTIONS ARE THERE FOR YOU?
Before you decide whether or not to be in this study, we will discuss other options that are 
available to you. Instead of being in this study, you could decide just to be treated for COVID-
19 in accordance with the current medical standard of care.
DISCUSSION OF FINDINGS
New information about the study
If we find out any new information that may affect your choice to participate in this study, we 
will get in touch with you to explain what we have learned. This may be information we have 
learned while doing this study here at the NIH or information we have learned from other 
scientists doing similar research in other places.
Return of research results
We do not plan to provide the results from any tests conducted for research purposes only with 
you or your doctor. However, the information we learn from looking at these research studies may 
benefit future patients. 
EARLY WITHDRAWAL FROM THE STUDY 
If at any time your doctor determines that it is no longer safe for you to take the study drug, the 
drug will be discontinued. If this happens, you will still need to complete blood tests and follow-
up visits described above.
STORAGE, SHARING AND FUTURE RESEARCH USING YOUR SPECIMENS AND DATA
As part of this study, we are obtaining specimens and data from you. We will remove all the 
identifiers, such as your name, date of birth, address, or medical record number and label your 
specimens and data with a code so that you cannot easily be identified. However, the code will 
be linked through a key to information that can identify you. 
Some of your specimens may be sent to our collaborators from other institutions, who will help 
us with research testing for this study. The specimens will be sent without any personal 
identification and could never be traced back to you.
Will your specimens or data be saved for use in other research studies?
We plan to store and use these specimens and data for studies other than the ones described in 
this consent form that are going on right now, as well as studies that may be conducted in the 
future. These studies may provide additional information that will be helpful in understanding 
COVID 19 or other diseases or conditions. This could include studies to develop other research 
tests, treatments, drugs, or devices, that may lead to the development of a commercial product 
by the NIH and/or its research or commercial partners. There are no plans to provide financial 
compensation to you if this happens. Also, it is unlikely that we will learn anything from these 
studies that may directly benefit you.
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
I give permission for my coded specimens and data to be stored and used for future research as 
described above.
_____ Yes
_____ No
Initials
Initials
Will your specimens or data be shared for use in other research studies?
We may share your coded specimens and data with other researchers.  If we do, while we will 
maintain the code key, we will not share it, so the other researchers will not be able to identify 
you.  They may be doing research in areas that are similar to this study or in other unrelated 
areas. These researchers may be at NIH, other research centers and institutions, or commercial 
entities.
I give permission for my coded specimens and data to be shared with other researchers and used 
by these researchers for future research as described above.
_____ Yes 
_____ No
Initials
Initials
If you change your mind and do not want us to store and use your specimens and data for future 
research, you should contact the research team member identified at the top of this document. 
We will do our best to comply with your request but cannot guarantee that we will always be 
able to destroy your specimens and data. For example, if some research with your specimens and 
data has already been completed, the information from that research may still be used. Also, for 
example, if the specimens and data have been shared already with other researchers, it might not 
be possible to withdraw them. 
In addition to the planned use and sharing described above, we might remove all identifiers and 
codes from your specimens and data and use or share them with other researchers for future 
research at the NIH or other places.  When we or the other researchers access your anonymized 
data, there will be no way to link the specimens or data back to you.  We will not contact you to 
ask your permission or otherwise inform you before we do this.  We might do this even if you 
answered "no" to the above questions.  If we do this, we would not be able to remove your 
specimens or data to prevent their use in future research studies, even if you asked, because we 
will not be able to tell which are your specimens or data.
NIH policies require that your clinical and other study data be placed in an internal NIH database 
that is accessible to other NIH researchers for future research. Usually, these researchers will not 
have access to any of your identifiers, such as your name, date of birth, address, or medical 
record number; and your data will be labeled with only a code. We cannot offer you a choice of 
whether your data to be placed in this database or not.  If you do not wish to have your data 
placed in this database, you should not enroll in this study.  
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
How long will your specimens and data be stored by the NIH?
Your specimens and data may be stored by the NIH possibly indefinitely, or until they are no 
longer of scientific value. 
Risks of storage and sharing of specimens and data
When we store your specimens and data, we take precautions to protect your information from 
others that should not have access to it. When we share your specimens and data, we will do 
everything we can to protect your identity, for example, when appropriate, we remove information 
that can identify you. Even with the safeguards we put in place, we cannot guarantee that your 
identity will never become known or someone may gain unauthorized access to your information. 
New methods may be created in the future that could make it possible to re-identify your specimens 
and data.
COMPENSATION, REIMBURSEMENT, AND PAYMENT
Will you receive compensation for participation in the study?
Some NIH Clinical Center studies offer compensation for participation in research. The amount 
of compensation, if any, is guided by NIH policies and guidelines.
You will receive compensation for the follow up visits after your hospital discharge:
•
$50 for each blood draw;
•
$20 for your first hour, and $10 for each subsequent hour spent at NIH Clinical Center 
during the follow up visit; 
•
If you are unable to finish the study, you will receive compensation only for the parts you 
completed.  
With few exceptions, study compensation is considered taxable income that is reportable to the 
Internal Revenue Service (IRS). A “Form 1099-Other Income” will be sent to you if your total 
payments for research participation are $600 or more in a calendar year. If you have unpaid debt 
to the federal government, please be aware that some or all of your compensation may be 
automatically reduced to repay that debt on your behalf.
Will you receive reimbursement or direct payment by NIH as part of your participation?
Some NIH Clinical Center studies offer reimbursement or payment for travel, lodging or meals 
while participating in the research. The amount, if any, is guided by NIH policies and guidelines.
This study does not offer reimbursement for, or payment of, lodging or meals. 
For the follow up visits to the NIH Clinical Center you will be reimbursed for your transportation 
expenses (car mileage, bus, metro, or taxi). If you prefer, NIH can arrange a taxi to take you to 
the NIH Clinical Center and back home.
Will taking part in this research study cost you anything? 
NIH does not bill health insurance companies or participants for any research or related clinical 
care that you receive at the NIH Clinical Center. 
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 02/05/2021
Page 10 of 13
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
CONFLICT OF INTEREST (COI) 
The NIH reviews NIH staff researchers at least yearly for conflicts of interest.  This process is 
detailed in a COI Guide.  You may ask your research team for a copy of the COI Guide or for more 
information.  Members of the research team who do not work for NIH are expected to follow these 
guidelines or the guidelines of their home institution, but they do not need to report their personal 
finances to the NIH.
The NIH and the research team for this study are using fostamatinib developed by Rigel 
Pharmaceuticals through a collaboration between your study team and the company. The company 
also provides financial support for this study.
CLINICAL TRIAL REGISTRATION AND RESULTS REPORTING 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.
CONFIDENTIALITY PROTECTIONS PROVIDED IN THIS STUDY  
Will your medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be kept 
private.  However, we cannot guarantee total privacy.  Organizations that may look at and/or copy 
your medical records for research, quality assurance, and data analysis include:
•
The NIH and other government agencies, like the Food and Drug Administration (FDA), 
which are involved in keeping research safe for people.
•
NIH Intramural Institutional Review Board
The researchers conducting this study and the NIH follow applicable laws and policies to keep 
your identifying information private to the extent possible.  However, there is always a chance 
that, despite our best efforts, your identity and/or information about your participation in this 
research may be inadvertently released or improperly accessed by unauthorized persons.
In most cases, the NIH will not release any identifiable information collected about you without 
your written permission.  However, your information may be shared as described in the section of 
this document on sharing of specimens and data, and as further outlined in the following sections.  
Further, the information collected for this study is protected by NIH under a Certificate of 
Confidentiality and the Privacy Act. 
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances.  
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court.  
The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical information 
that we collect under the authority of the Public Health Service Act.  In some cases, the Privacy 
Act protections differ from the Certificate of Confidentiality.  For example, sometimes the Privacy 
Act allows release of information from your record without your permission, for example, if it is 
requested by Congress. Information may also be released for certain research purposes with due 
consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting,  to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit.  However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
POLICY REGARDING RESEARCH-RELATED INJURIES  
The NIH Clinical Center will provide short-term medical care for any injury resulting from your 
participation in research here. In general, no long-term medical care or financial compensation for 
research-related injuries will be provided by the NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
The NIH Clinical Center will provide short-term medical care for any injury resulting from your 
participation in research here. In general, no long-term medical care will be provided by the NIH, 
the NIH Clinical Center, or the Federal Government. A Declaration under the Public Readiness 
and Emergency Preparedness (PREP) Act was issued by  the  Secretary  of  the  United  States  
Department  of  Health  and  Human  Services  on  March  10, 2020.  This Declaration limits the 
legal rights of a subject participating in clinical studies utilizing COVID-19 countermeasures.  
Because this study is covered by the PREP Act Declaration, covered persons,  such  as  the  
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Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
manufacturers,  study  sponsor,  researchers,  healthcare  providers  and  others have liability 
immunity (that is, they cannot be sued by you or your family under the laws of the United States). 
If you believe that you may have been harmed as a result of this research study, certain claims for 
serious injury or death caused by the countermeasure may be eligible for compensation through
the Countermeasures Injury Compensation Program. This is a program set up by the United States 
Government.  Information        about        this        program        can        be        found        at 
https://www.hrsa.gov/cicp/about/index.html or by calling 1-855-266-2427.
PROBLEMS OR QUESTIONS
If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Jeffrey Strich, 
strichj@niaid.nih.gov; 301-496-9320. 
You may also call the NIH Clinical Center Patient Representative at 301-496-2626, or the NIH 
Office of IRB Operations at 301-402-3713, if you have a research-related complaint or concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.
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Consent to Participate in a Clinical Research Study
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Adult Research Participant: I have read the explanation about this study and have been given the opportunity 
to discuss it and to ask questions. I consent to participate in this study.
Signature of Research Participant
Print Name of Research Participant
Date
Legally Authorized Representative (LAR) for an Adult Unable to Consent: I have read the explanation 
about this study and have been given the opportunity to discuss it and to ask questions. I am legally authorized 
to make research decisions on behalf of the adult participant unable to consent and have the authority to provide 
consent to this study. As applicable, the information in the above consent was described to the adult participant 
unable to consent who agrees to participate in the study.
Signature of LAR
Print Name of LAR
Date
Investigator:
Signature of Investigator
Print Name of Investigator
Date
Witness to the oral short-form consent process only: 
Signature of Witness*
Print Name of Witness
Date
*NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN 
INTERPRETER:
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent and served as a witness. The investigator obtaining consent may not 
also serve as the witness.
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent but did not serve as a witness. The name or ID code of the person 
providing interpretive support is:
.
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