Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Fostamatinib for Hospitalized Adults With COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04579393
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : November 10, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

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 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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Single Group 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 : October 8, 2020
Estimated Primary Completion Date : December 15, 2020
Estimated Study Completion Date : December 15, 2020

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Cumulative Incidence of SAEs [ Time Frame: Day 29 ]
    The safety primary endpoint is cumulative incidence of SAEs through day 29


Secondary Outcome Measures :
  1. Number of days in the ICU [ Time Frame: entire hospitalization ]
  2. 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 ]
  3. Ordinal scale [ Time Frame: day 15, 29 ]
  4. Days of hospitalization [ Time Frame: entire hospitalization ]
  5. Time to recovery [ Time Frame: day 29 ]
  6. Number of days free of mechanical ventilation [entire hospitalization cohort 1] [ Time Frame: entire hospitalization ]
  7. Number of days on oxygen [ Time Frame: entire hospitalization ]
  8. Change in SOFA score from baseline [ Time Frame: day 3, 5, 8, 11, 15, 29 ]
  9. Days free of renal failure [ Time Frame: entire hospitalization ]
  10. Clinically relevant deep vein thrombosis [ Time Frame: entire hospitalization ]
  11. Relative change in PaO2/FiO2 or SpO2/FiO2 ratio [ Time Frame: day 1,3,5,8,15,22 and 29 ]
  12. Mortality [ Time Frame: day 14, 18 ]
  13. Grade 3 and 4 AE [ Time Frame: through day 60 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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), or B-cell depleting antibody in the prior 6 months (rituximab, other anti-CD20 mAb)
  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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Jennifer J Kyte, D.N.P. (301) 827-0367 jennifer.kyte@nih.gov

Locations
Layout table for location information
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    prpl@cc.nih.gov   
United States, Virginia
INOVA Health Systems Recruiting
Falls Church, Virginia, United States, 22042
Contact: Edwinia Battle    703-776-3067    edwinia.battle@inova.org   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Jeffrey R Strich, M.D. National Institutes of Health Clinical Center (CC)
Additional Information:
Layout table for additonal information
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT04579393    
Other Study ID Numbers: 10000110
000110-H
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: November 10, 2020
Last Verified: November 6, 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
SARS-CoV-2
Cytokines
Spleen Tyrosine Kinase
ARDS
Additional relevant MeSH terms:
Layout table for MeSH terms
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases