Fostamatinib for Hospitalized Adults With COVID-19
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|ClinicalTrials.gov Identifier: NCT04579393|
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : November 10, 2020
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.
To learn if fostamatinib is safe in patients who are hospitalized with COVID-19 and gain earlier insight into whether it improves outcomes.
Adults age 18 and older who are hospitalized with COVID-19.
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|
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 approximately 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Phase II Study Evaluating Fostamatinib for Hospitalized Adults With COVID-19|
|Actual Study Start Date :||October 8, 2020|
|Estimated Primary Completion Date :||December 15, 2020|
|Estimated Study Completion Date :||December 15, 2020|
Active Comparator: Intervention
fostamatinib in combination with standard of care (SOC) for the treatment of COVID-19
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
Placebo tablets to match fostamatinib 100 mg and 150 mg will be provided.
- Cumulative Incidence of SAEs [ Time Frame: Day 29 ]The safety primary endpoint is cumulative incidence of SAEs through day 29
- Number of days in the ICU [ Time Frame: entire hospitalization ]
- Change in CRP, IL-6, d-dimer, ferritin, fibrinogen, absolute lymphocyte count, absolute neutrophil count, and platelet count from baseline [ Time Frame: day 3, 5, 8, 11, 15, 29 ]
- Ordinal scale [ Time Frame: day 15, 29 ]
- Days of hospitalization [ Time Frame: entire hospitalization ]
- Time to recovery [ Time Frame: day 29 ]
- Number of days free of mechanical ventilation [entire hospitalization cohort 1] [ Time Frame: entire hospitalization ]
- Number of days on oxygen [ Time Frame: entire hospitalization ]
- Change in SOFA score from baseline [ Time Frame: day 3, 5, 8, 11, 15, 29 ]
- Days free of renal failure [ Time Frame: entire hospitalization ]
- Clinically relevant deep vein thrombosis [ Time Frame: entire hospitalization ]
- Relative change in PaO2/FiO2 or SpO2/FiO2 ratio [ Time Frame: day 1,3,5,8,15,22 and 29 ]
- Mortality [ Time Frame: day 14, 18 ]
- Grade 3 and 4 AE [ Time Frame: through day 60 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04579393
|Contact: Jennifer J Kyte, D.N.P.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|United States, Virginia|
|INOVA Health Systems||Recruiting|
|Falls Church, Virginia, United States, 22042|
|Contact: Edwinia Battle 703-776-3067 firstname.lastname@example.org|
|Principal Investigator:||Jeffrey R Strich, M.D.||National Institutes of Health Clinical Center (CC)|