International Sites: Novel Experimental COVID-19 Therapies Affecting Host Response

Phase 2

Terminated

Conditions: COVID-19
Coronavirus Infection
SARS-CoV2 Infection

Interventions: Drug: Placebo
Drug: Fostamatinib

Registration Number: NCT05593770

Lead Sponsor: NEAT ID Foundation

Brief Summary: The overarching goal of the Master Protocol is to find effective strategies for inpatient management of patients with COVID-19. Therapeutic goals for patients hospitalized for COVID-19 include hastening recovery and preventing progression to critical illness, multiorgan failure, or death. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19.

Detailed Description: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. The clinical spectrum of COVID-19 infection is broad, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and death. Between 13 and 40% of patients become hospitalized, up to 30% of those hospitalized require admission for intensive care, and there is a 13% inpatient mortality rate. The reasons for hospitalization include respiratory support, as well as support for failure of other organs, including the heart and kidneys. The risk of thrombotic complications is increased, even when compared to other viral respiratory illnesses, such as influenza. While 82% of hospitalized patients with COVID-19 are ultimately discharged alive, median length of stay is 10-13 days.

Early work in treating COVID-19 has focused on preventing worsening of the initial clinical presentation to prevent hospitalization and disease progression to organ failure and death. Studies conducted under this Master Host Tissue Protocol are expected to extend our knowledge of how to manage patients who are hospitalized for COVID-19 illness. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19. This Master Protocol is a randomized, placebo-controlled trial of agents targeting the host response in COVID-19 in hospitalized patients with hypoxemia. The Master Host Tissue Protocol is designed to be flexible in the number of study arms, the use of a single placebo group, and the stopping and adding of new therapies. Our primary outcome is oxygen free days through day 28. This is defined as days alive and without supplemental oxygen use during the first 28 days following randomization. Patients who die on or before day 28 are assigned -1 oxygen free days.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 28

Inclusion Criteria

Hospitalized for COVID-19
≥18 years of age
SARS-CoV-2 infection, documented by:
1. nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR
2. documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non- NAT tests is maintained in Appendix E. Appendix E. Non-NAT Tests Deemed with Equivalent Specificity to NAT by the Protocol Team).
Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy
Symptoms or signs of acute COVID-19, defined as one or more of the following:
1. cough
2. reported or documented body temperature of 100.4 degrees Fahrenheit or greater
3. shortness of breath
4. chest pain
5. infiltrates on chest imaging (x-ray, CT scan, lung ultrasound)

Exclusion Criteria

Onset of COVID-19 symptom fulfilling inclusion criterion #5 >14 days prior to randomization
Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission)
Pregnancy
Breastfeeding
Prisoners
End-stage renal disease (ESRD) on dialysis
Patient undergoing comfort care measures only such that treatment focuses on end-of- life symptom management over prolongation of life.
The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient
Known allergy/hypersensitivity to IMP or its excipients

Fostamatinib Arm-Specific Exclusion Criteria:

The following exclusion criteria differ from the master protocol criteria:

Randomized in another trial evaluating fostamatinib in the prior 30 days

Study arm exclusion criteria measured within 24 hours prior to randomization:

AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN
SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization
ANC < 1000/mL
Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib,Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx.
Patient unable to participate or declines participation in the fostamatinib arm.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Orange film-coated, plain, bioconvex tablets for fostamatinib. For the purposes of interim and final analyses, the route and frequency of placebo will be ignored, and all placebo participants will be pooled together as a single group. In comparing an active drug versus placebo, only those placebo participants that were eligible for the active drug will be included.
Fostamatinib	Fostamatinib	An investigational oral spleen tyrosine kinase inhibitor.

Primary Outcome Measures

Name	Time	Method
Oxygen Free Days Through Day 28	Day 1 to Day 28	This is defined as days alive and without supplemental oxygen use during the first 28 days following randomization. Patients who die on or before day 28 are assigned -1 oxygen free days. Patients will be considered to be receiving supplemental oxygen therapy when they are receiving any of the following: supplemental oxygen by nasal cannula, supplemental oxygen by face mask, high flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).

Secondary Outcome Measures

Name	Time	Method
In-hospital Mortality	Day 1 to hospital discharge or Day 90 whichever comes first	Number of patients who die during hospitalization
28-day Mortality	Day 28	Number of patients who have died at Day 28
60-day Mortality	Day 60	Number of patients who have died at Day 60
90-day Mortality	Day 90	Number of participants mortality at Day 90
Alive and Oxygen Free at Day 14	Day 1 to Day 14	Number of patients oxygen free at day 14. Patients will be considered to be receiving supplemental oxygen therapy when they are receiving any of the following: supplemental oxygen by nasal cannula, supplemental oxygen by face mask, high flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
Alive and Oxygen Free at Day 28	Day 1 to Day 28	Number of patients oxygen free at day 28. Patients will be considered to be receiving supplemental oxygen therapy when they are receiving any of the following: supplemental oxygen by nasal cannula, supplemental oxygen by face mask, high flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO)
Alive and Free of New Invasive Mechanical Ventilation at Day 28	Day 1 to Day 28	Number of patients alive free of new invasive mechanical ventilation at day 28
Clinical Status Assessed Using World Health Organization (WHO) 8-point Ordinal Scale at Day 14	Day 14	Number of participants who fell within the ordinal scale per the below criteria. A higher score indicates a worse outcome. 1. Ambulatory - Not hospitalized and no limitation of activities 2. Ambulatory - Not hospitalized with limitation of activities or home oxygen use 3. Hospitalized Mild Disease - Hospitalized, no oxygen therapy 4. Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs 5. Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula 6. Hospitalized Severe Disease -Invasive mechanical ventilation 7. Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO 8. Dead
Clinical Status Assessed Using WHO 8-point Ordinal Scale at Day 28	Day 28	The number of participants who fell within the ordinal scale per the below criteria. A higher score means a worse outcome 1. Ambulatory - Not hospitalized and no limitation of activities 2. Ambulatory - Not hospitalized with limitation of activities or home oxygen use 3. Hospitalized Mild Disease - Hospitalized, no oxygen therapy 4. Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs 5. Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula 6. Hospitalized Severe Disease -Invasive mechanical ventilation 7. Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO 8. Dead
Clinical Status Assessed Using WHO 8-point Ordinal Scale at Day 60	Day 60	Number of participants who fell within the ordinal scale per the below criteria. A higher score means a worse outcome 1. Ambulatory - Not hospitalized and no limitation of activities 2. Ambulatory - Not hospitalized with limitation of activities or home oxygen use 3. Hospitalized Mild Disease - Hospitalized, no oxygen therapy 4. Hospitalized Mild Disease - Hospitalized, oxygen by mask or nasal prongs 5. Hospitalized Severe Disease - Non-invasive ventilation or high-flow nasal cannula 6. Hospitalized Severe Disease -Invasive mechanical ventilation 7. Hospitalized Severe Disease - Invasive mechanical ventilation plus additional organ support with- vasopressors, RRT, or ECMO 8. Dead
Hospital-free Days Through Day 28	Day 1 to Day 28	Days alive and not hospitalized during the first 28 days following randomization. Patients who die on or before day 28 are assigned a value -1.
Ventilator-free Days Through Day 28	Day 1 to Day 28	Days alive and not receiving mechanical ventilation during the first 28 days following randomization. Patients who die on or before day 28 are assigned a value -1.
Respiratory Failure-free Days Through Day 28	Day 1 to Day 28	Days alive and not in respiratory failure during the first 28 days following randomization. A respiratory failure-free day is defined as a day alive without the use of HFNC, NIV, IMV, or (ECMO). Patients who die on or before day 28 are assigned a value -1.

Trial Locations

Locations (21): Global Clinical Trials (Pty) Ltd
🇿🇦
Pretoria, South Africa
Clinical HIV Research Unit - Helen Joseph Hospital (WITS CHRU)
🇿🇦
Johannesburg, South Africa
Hospital Clinic Barcelona
🇪🇸
Barcelona, Villarroel, Spain
Hospital General Universitario de Elche
🇪🇸
Alicante, Spain
University Hospital Bonn
🇩🇪
Bonn, Germany
University of Frankfurt
🇩🇪
Frankfurt, Germany
Universidad de Valladolid - Hospital Universitario Río Hortega
🇪🇸
Valladolid, Spain
Hospital Federal dos Servidores do Estado
🇧🇷
Rio De Janeiro, Brazil
Hospital Universitario Fundacion Alcorcon
🇪🇸
Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸
Madrid, Spain
Worthwhile Clinical Trials (WWCT Lakeview Hospital)
🇿🇦
Benoni, South Africa
Hospital de Clínicas de Porto Alegre
🇧🇷
Porto Alegre, Brazil
San Paolo Hospital - ASST Santi Paolo e Carlo
🇮🇹
Milan, Italy
University of Milan
🇮🇹
Milan, Italy
Ente Ospedaliero Ospedali Galliera
🇮🇹
Genova, Italy
Instituto Nacional de Infectologia Evandro Chagas
🇧🇷
Rio De Janeiro, Brazil
San Raffaele Turro Hospital
🇮🇹
Milan, Italy
Hospital del Mar
🇪🇸
Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸
Zaragoza, Spain
Hospital Clinico San Carlos
🇪🇸
Madrid, Spain