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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
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Tracking Information
First Submitted Date  ICMJE October 6, 2020
First Posted Date  ICMJE October 8, 2020
Last Update Posted Date November 10, 2020
Actual Study Start Date  ICMJE October 8, 2020
Estimated Primary Completion Date December 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2020)
Cumulative Incidence of SAEs [ Time Frame: Day 29 ]
The safety primary endpoint is cumulative incidence of SAEs through day 29
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2020)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2020)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fostamatinib for Hospitalized Adults With COVID-19
Official Title  ICMJE A Phase II Study Evaluating Fostamatinib for Hospitalized Adults With COVID-19
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 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Coronavirus Disease 2019
Intervention  ICMJE
  • Drug: Placebo
    Placebo tablets to match fostamatinib 100 mg and 150 mg will be provided.
  • 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.
Study Arms  ICMJE
  • Active Comparator: Intervention
    fostamatinib in combination with standard of care (SOC) for the treatment of COVID-19
    Intervention: Drug: fostamatinib
  • Placebo Comparator: Intervention - Placebo
    Placebo in combination with standard of care (SOC) for the treatment of COVID-19
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 5, 2020)
80
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2020)
60
Estimated Study Completion Date  ICMJE December 15, 2020
Estimated Primary Completion Date December 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer J Kyte, D.N.P. (301) 827-0367 jennifer.kyte@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04579393
Other Study ID Numbers  ICMJE 10000110
000110-H
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
Study Sponsor  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey R Strich, M.D. National Institutes of Health Clinical Center (CC)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date November 6, 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP