Fostamatinib for Hospitalized Adults With COVID-19

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT04579393
• Collaborator: (none)
• Enrollment: 59
• Locations: 2
• Arms: 2
• Actual Duration (Months): 6.7
• Patients Per Site: 29.5
• Patients Per Site Per Month: 4.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Disease 2019	Drug: Placebo; Drug: fostamatinib	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Evaluating Fostamatinib for Hospitalized Adults With COVID-19
• Actual Study Start Date: Oct 8, 2020
• Actual Primary Completion Date: Mar 30, 2021
• Actual Study Completion Date: Apr 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention fostamatinib in combination with standard of care (SOC) for the treatment of COVID-19	Drug: fostamatinib; 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.
Placebo Comparator: Intervention - Placebo Placebo in combination with standard of care (SOC) for the treatment of COVID-19	Drug: Placebo; Placebo tablets to match fostamatinib 100 mg and 150 mg will be provided.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With at Least 1 Serious Adverse Event [Day 29]

   Number of participants with at least 1 serious adverse event by day 29 using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CTCAE is a list of common adverse event (AE) terms. Each AE term is defined and accompanied by a grading scale (1 to 5) that indicates the severity of the AE. Grading ranges from Grade 1 which is mild to Grade 5 which is death.

Secondary Outcome Measures

1. Number of Participants With Sustained Recoveries Defined by Ordinal Scale Score of 3 or Less [day 29]

   Time to sustained recovery determined by ordinal scale score of 3 or less and defined as time to recovery [either discharge from the hospital or hospitalization for infection control reasons only], with the recovery status sustained through day 29. The ordinal scale is an assessment of the clinical status. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

2. Number of Participants Who Progress to Mechanical Ventilation [day 29]

   Number of participants who progress to mechanical ventilation by day 29

3. Number of Participants With Cumulative Clinical Endpoint of Death [day 14, day 28, day 60]

   Number of Participants with Cumulative Clinical Endpoint of Death at Day 14, Day 28 and Day 60

4. Number of Grade 3 and 4 Adverse Events Through Day 60 [Day 60]

   Number of Grade 3 and 4 AE through day 60 using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CTCAE is a list of common adverse event (AE) terms. Each AE term is defined and accompanied by a grading scale (1 to 5) that indicates the severity of the AE. Grading ranges from Grade 1 which is mild to Grade 5 which is death.

5. Participant Score on Ordinal Scale [Day 15, Day 29]

   Participant score on ordinal scale at day 15 and day 29. The ordinal scale is an assessment of the clinical status. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

6. Change in C-Reactive Protein Levels From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

   Change in C-Reactive Protein (CRP) blood levels from baseline. The upper limit of normal is 5 mg/L (milligrams per liter).

7. Change in Fibrinogen Levels From Baseline. [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

   Change in Fibrinogen blood levels from baseline. The upper limit of normal is Fibrinogen 466 milligrams per decilitre (mg/dL).

8. Change in D-Dimer Levels From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

   Change in D-Dimer blood levels from baseline. The upper limit of normal is 0.50 mcg/mL (microgram per milliliter).

9. Change in Ferritin Levels From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

   Change in Ferritin levels from baseline. The upper limit of normal for Ferritin is 400 mcg/L (micrograms per liter).

10. Change in Interleukin 6 (IL6) Levels From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

    Change in Interleukin 6 (IL6) blood levels from baseline. The upper limit of normal for IL6 is 1.8 picograms per milliliter (pg/mL).

11. Median Days Participants Were Admitted to Intensive Care Unit [Day 29]

    Median days participants were admitted to Intensive Care Unit (ICU) by day 29

12. Relative Change in SpO2/FiO2 Ratio [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

    Relative change in PaO2/FiO2 or SpO2/FiO2 ratio.

13. Change in SOFA Score From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

    Change in SOFA score from baseline (day 1). The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems. The score is calculated on admission and every 24 hours until discharge using the worst parameters measured during the prior 24 hours. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). The "worst" measurement was defined as the measure that correlated to the highest number of points. The SOFA score ranges from 0 to 24.

14. Median Days on Participants Received Supplemental Oxygen [day 29]

    Median days on participants received supplemental oxygen through day 29

15. The Number of Participants That Experienced Acute Renal Failure [day 29]

    The number of participants that experienced acute renal failure by day 29. Acute renal failure defined as increase in serum creatinine by ≥0.3mg/dL within 48 hours or increase in serum creatinine by ≥1.5 times baseline which is known or presumed to have occurred within the prior seven days.

16. Number of Participants That Experienced a Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) [day 29]

    Number of participants that experienced a deep vein thrombosis (DVT) or pulmonary embolism (PE) by day 29

17. Change in Absolute Lymphocyte Count Levels From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

    Change in Absolute lymphocyte count blood levels from baseline.

18. Change in Absolute Neutrophil Count Levels From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

    Change in Absolute neutrophil count blood levels from baseline.

19. Change in Platelet Count Levels From Baseline [Day 3, Day 5, Day 8, Day 11, Day 15, Day 29]

    Change in Platelet count blood levels from baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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)

EXCLUSION CRITERIA:

1. ALT or AST > 5 times the upper limit of normal (ULN) or ALT or AST >= 3 x ULN and total bilirubin > 2 x ULN.

2. Estimated glomerular filtration rate (eGFR) <30ml/min

3. Pregnancy or breast feeding

4. Anticipated discharge in the next 72 hours

5. Allergy to study medication

6. Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood pressure >100mmHg)

7. Shock or hypotension at the time of enrollment

8. Neutrophil count <1000/microliter

9. Concern for bacterial or fungal sepsis

10. 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)

11. Received a live vaccine the last 4 weeks

12. Those who were cognitively impaired or mentally disabled prior to COVID diagnosis

13. Participation in another clinical trial for the treatment of COVID-19.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892
2	INOVA Health Systems	Falls Church	Virginia	United States	22042

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Jeffrey R Strich, M.D., National Institutes of Health Clinical Center (CC)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 17, 2020
• Informed Consent Form - Feb 5, 2021

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT04579393
• Other Study ID Numbers: 10000110; 000110-H
• First Posted: Oct 8, 2020
• Last Update Posted: Mar 2, 2022
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): SARS-CoV-2; Cytokines; Spleen Tyrosine Kinase; ARDS
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from October 8, 2020, through March 2, 2021 across 2 centers: Inova Fairfax Hospital (Falls Church, VA) and the National Institutes of Health (NIH) Clinical Center (Bethesda, MD).

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Period Title: Overall Study
STARTED	30	29
COMPLETED	27	24
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19	Total
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Total of all reporting groups
Overall Participants	30	29	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.3 (13.5)	57.0 (14.1)	55.6 (13.7)
Sex: Female, Male (Count of Participants)
Female	8 26.7%	4 13.8%	12 20.3%
Male	22 73.3%	25 86.2%	47 79.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 60%	17 58.6%	35 59.3%
Not Hispanic or Latino	12 40%	12 41.4%	24 40.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 6.7%	4 13.8%	6 10.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 10%	3 10.3%	6 10.2%
White	12 40%	11 37.9%	23 39%
More than one race	1 3.3%	0 0%	1 1.7%
Unknown or Not Reported	12 40%	11 37.9%	23 39%
Region of Enrollment (participants) [Number]
United States	30 100%	29 100%	59 100%
Score on Ordinal Scale (Count of Participants)
Requiring supplemental oxygen	11 36.7%	12 41.4%	23 39%
Noninvasive ventilation or high-flow oxygen devices	17 56.7%	15 51.7%	32 54.2%
Invasive mechanical ventilation or extracorporeal membrane oxygen	2 6.7%	2 6.9%	4 6.8%
Medication for COVID-19 other than the study drug (participants) [Number]
Remdesivir	30 100%	29 100%	59 100%
Dexamethasone or other steroids (methylprednisolone and prednisone)	30 100%	29 100%	59 100%
Convalescent plasma or monoclonal antibodies	12 40%	13 44.8%	25 42.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With at Least 1 Serious Adverse Event
Description	Number of participants with at least 1 serious adverse event by day 29 using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CTCAE is a list of common adverse event (AE) terms. Each AE term is defined and accompanied by a grading scale (1 to 5) that indicates the severity of the AE. Grading ranges from Grade 1 which is mild to Grade 5 which is death.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
Count of Participants [Participants]	3 10%	6 20.7%

2. Secondary Outcome

Title	Number of Participants With Sustained Recoveries Defined by Ordinal Scale Score of 3 or Less
Description	Time to sustained recovery determined by ordinal scale score of 3 or less and defined as time to recovery [either discharge from the hospital or hospitalization for infection control reasons only], with the recovery status sustained through day 29. The ordinal scale is an assessment of the clinical status. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame	day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
Count of Participants [Participants]	27 90%	22 75.9%

3. Secondary Outcome

Title	Number of Participants Who Progress to Mechanical Ventilation
Description	Number of participants who progress to mechanical ventilation by day 29
Time Frame	day 29

Outcome Measure Data

Analysis Population Description

Participants who were not receiving mechanical ventilation at baseline

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	28	27
Count of Participants [Participants]	1 3.3%	2 6.9%

4. Secondary Outcome

Title	Number of Participants With Cumulative Clinical Endpoint of Death
Description	Number of Participants with Cumulative Clinical Endpoint of Death at Day 14, Day 28 and Day 60
Time Frame	day 14, day 28, day 60

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
day 14	0 0%	1 3.4%
day 28	0 0%	3 10.3%
day 60	1 3.3%	3 10.3%

5. Secondary Outcome

Title	Number of Grade 3 and 4 Adverse Events Through Day 60
Description	Number of Grade 3 and 4 AE through day 60 using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CTCAE is a list of common adverse event (AE) terms. Each AE term is defined and accompanied by a grading scale (1 to 5) that indicates the severity of the AE. Grading ranges from Grade 1 which is mild to Grade 5 which is death.
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
Grade 3	17	23
Grade 4	3	7

6. Secondary Outcome

Title	Participant Score on Ordinal Scale
Description	Participant score on ordinal scale at day 15 and day 29. The ordinal scale is an assessment of the clinical status. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame	Day 15, Day 29

Outcome Measure Data

Analysis Population Description

intent to treat analysis

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
Day 15	1	2
Day 29	1	1

7. Secondary Outcome

Title	Change in C-Reactive Protein Levels From Baseline
Description	Change in C-Reactive Protein (CRP) blood levels from baseline. The upper limit of normal is 5 mg/L (milligrams per liter).
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	-37	-46
Day 5	-34	-51
Day 8	-56	-66
Day 11	-52	-68
Day 15	-43	-71
Day 29	-65	-106

8. Secondary Outcome

Title	Change in Fibrinogen Levels From Baseline.
Description	Change in Fibrinogen blood levels from baseline. The upper limit of normal is Fibrinogen 466 milligrams per decilitre (mg/dL).
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	-60	-65
Day 5	-86	-78
Day 8	-130	-96
Day 11	-141	-138
Day 15	-132	-76
Day 29	-113	-231

9. Secondary Outcome

Title	Change in D-Dimer Levels From Baseline
Description	Change in D-Dimer blood levels from baseline. The upper limit of normal is 0.50 mcg/mL (microgram per milliliter).
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	-0.01	-0.08
Day 5	-0.06	-0.1
Day 8	-0.15	-0.24
Day 11	-0.11	-0.43
Day 15	-0.06	-0.32
Day 29	-0.15	-0.16

10. Secondary Outcome

Title	Change in Ferritin Levels From Baseline
Description	Change in Ferritin levels from baseline. The upper limit of normal for Ferritin is 400 mcg/L (micrograms per liter).
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	-94	-190
Day 5	-213	-199
Day 8	-73	-253
Day 11	-169	-491
Day 15	-346	-561
D29	-578	-738

11. Secondary Outcome

Title	Change in Interleukin 6 (IL6) Levels From Baseline
Description	Change in Interleukin 6 (IL6) blood levels from baseline. The upper limit of normal for IL6 is 1.8 picograms per milliliter (pg/mL).
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	-0.7	1.4
Day 5	-1	0.3
Day 8	0	-2.5
Day 11	-0.1	-0.3
Day 15	-1.5	-0.7
Day 29	-1.4	-1.4

12. Secondary Outcome

Title	Median Days Participants Were Admitted to Intensive Care Unit
Description	Median days participants were admitted to Intensive Care Unit (ICU) by day 29
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

Participants admitted to Intensive Care Unit

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	13	12
Median (Inter-Quartile Range) [Days]	3	7

13. Secondary Outcome

Title	Relative Change in SpO2/FiO2 Ratio
Description	Relative change in PaO2/FiO2 or SpO2/FiO2 ratio.
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Only SpO2/FiO2 ratio is available as PaO2 was not consistently measured. Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	0.87	0.93
Day 5	1.09	0.88
Day 8	0.75	1.09
Day 11	1.49	0.99
Day 15	1.23	1.07
Day 29	0.74	0.49

14. Secondary Outcome

Title	Change in SOFA Score From Baseline
Description	Change in SOFA score from baseline (day 1). The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems. The score is calculated on admission and every 24 hours until discharge using the worst parameters measured during the prior 24 hours. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). The "worst" measurement was defined as the measure that correlated to the highest number of points. The SOFA score ranges from 0 to 24.
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	0	0
Day 5	0	0
Day 8	0	0
Day 11	0	0
Day 15	-1	0
Day 29	0	1

15. Secondary Outcome

Title	Median Days on Participants Received Supplemental Oxygen
Description	Median days on participants received supplemental oxygen through day 29
Time Frame	day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
Median (Inter-Quartile Range) [days]	8	20

16. Secondary Outcome

Title	The Number of Participants That Experienced Acute Renal Failure
Description	The number of participants that experienced acute renal failure by day 29. Acute renal failure defined as increase in serum creatinine by ≥0.3mg/dL within 48 hours or increase in serum creatinine by ≥1.5 times baseline which is known or presumed to have occurred within the prior seven days.
Time Frame	day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
Count of Participants [Participants]	3 10%	5 17.2%

17. Secondary Outcome

Title	Number of Participants That Experienced a Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
Description	Number of participants that experienced a deep vein thrombosis (DVT) or pulmonary embolism (PE) by day 29
Time Frame	day 29

Outcome Measure Data

Analysis Population Description

Intent to Treat Analysis.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	30	29
Count of Participants [Participants]	2 6.7%	0 0%

18. Secondary Outcome

Title	Change in Absolute Lymphocyte Count Levels From Baseline
Description	Change in Absolute lymphocyte count blood levels from baseline.
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	0.43	0.13
Day 5	0.48	0.38
Day 8	0.41	0.34
Day 11	1.03	1.02
Day 15	1.03	0.68
Day 29	0.56	0.81

19. Secondary Outcome

Title	Change in Absolute Neutrophil Count Levels From Baseline
Description	Change in Absolute neutrophil count blood levels from baseline.
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	0.04	-0.09
Day 5	1.53	0.94
Day 8	0.63	2.74
Day 11	-0.95	0.85
Day 15	-1.77	-1.6
Day 29	-2.54	-2.89

20. Secondary Outcome

Title	Change in Platelet Count Levels From Baseline
Description	Change in Platelet count blood levels from baseline.
Time Frame	Day 3, Day 5, Day 8, Day 11, Day 15, Day 29

Outcome Measure Data

Analysis Population Description

Intent to treat analysis. 58 patients (29 in each group) provided research samples for at least one time-point since baseline except for one patient who did not take any study drug and withdrew consent after enrollment.

Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19	Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.	Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
Measure Participants	29	29
Day 3	59	58
Day 5	103	63
Day 8	145	62
Day 11	80	25
Day 15	11	-26
Day 29	-29	-7

Adverse Events

Time Frame	60 days
Arm/Group Title	Fostamatinib With Standard of Care for Treatment of COVID-19		Placebo With Standard of Care for Treatment of COVID-19
Arm/Group Description	Fostamatinib, will be administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.		Placebo: Placebo tablets to match fostamatinib 150 mg will be provided and administered orally at a dose of 150 mg twice daily for 14 days or 28 doses.
All Cause Mortality
	Fostamatinib With Standard of Care for Treatment of COVID-19		Placebo With Standard of Care for Treatment of COVID-19
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		3/29 (10.3%)
Serious Adverse Events
	Fostamatinib With Standard of Care for Treatment of COVID-19		Placebo With Standard of Care for Treatment of COVID-19
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/30 (16.7%)		10/29 (34.5%)
Endocrine disorders
Hypoglycemia	1/30 (3.3%)	1	0/29 (0%)	1
Gastrointestinal disorders
Bleeding	1/30 (3.3%)	1	0/29 (0%)	1
General disorders
Multi-organ failure	0/30 (0%)	0	1/29 (3.4%)	1
Immune system disorders
Allergic reaction	0/30 (0%)	0	1/29 (3.4%)	1
Infections and infestations
Lung infection	0/30 (0%)	0	1/29 (3.4%)	1
Metabolism and nutrition disorders
Acidosis	0/30 (0%)	0	1/29 (3.4%)	1
Renal and urinary disorders
Acute kidney injury	0/30 (0%)	0	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/30 (6.7%)	2	3/29 (10.3%)	3
ACUTE RESPIRATORY FAILURE	1/30 (3.3%)	1	0/29 (0%)	1
Self-Extubation	0/30 (0%)	0	1/29 (3.4%)	1
Post COVID Fibrosis	0/30 (0%)	0	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	Fostamatinib With Standard of Care for Treatment of COVID-19		Placebo With Standard of Care for Treatment of COVID-19
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/30 (26.7%)		15/29 (51.7%)
Blood and lymphatic system disorders
Anemia	0/30 (0%)	0	3/29 (10.3%)	3
Investigations
Lymphocyte count decreased	4/30 (13.3%)	4	7/29 (24.1%)	7
Metabolism and nutrition disorders
Hypoalbuminemia	2/30 (6.7%)	2	3/29 (10.3%)	3
Hypokalemia	2/30 (6.7%)	2	1/29 (3.4%)	1
Hypocalcemia	0/30 (0%)	0	2/29 (6.9%)	2
Vascular disorders
Thromboembolic event	2/30 (6.7%)	2	0/29 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.