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

NCT05593770 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: ACTIV-4
• Study Type: interventional
• Target: 28
• Locations: 5 countries
• Sites: 21

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.

Conditions

COVID-19; SARS-CoV2 Infection; Coronavirus Infection

Outcome Measures

Primary Outcomes (1)

• 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. 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).

  Day 1 to Day 28

Secondary Outcomes (13)

• In-hospital Mortality

  Day 1 to hospital discharge or Day 90 whichever comes first

• Alive and Oxygen Free at Day 14

  Day 1 to Day 14

• Alive and Oxygen Free at Day 28

  Day 1 to Day 28

• Alive and Free of New Invasive Mechanical Ventilation at Day 28

  Day 1 to Day 28

• 28-day Mortality

  Day 28

Study Arms (2)

Fostamatinib

EXPERIMENTAL

An investigational oral spleen tyrosine kinase inhibitor.

Drug: Fostamatinib

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Fostamatinib DRUG

Fostamatinib100-150mg orally twice daily for 14 days or 28 doses. Study medication will be continued as an outpatient if the patient is discharged prior to completing 28 doses.

Fostamatinib

Placebo DRUG

Orange film-coated, plain bioconvex tablets orally twice daily for 14 days or 28 doses for fostamatinib. Study medication will be continued as an outpatient if the patient is discharged prior to completing 28 doses.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized for COVID-19
• ≥18 years of age
• SARS-CoV-2 infection, documented by:
• nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR
• 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:
• cough
• reported or documented body temperature of 100.4 degrees Fahrenheit or greater
• shortness of breath
• chest pain
• infiltrates on chest imaging (x-ray, CT scan, lung ultrasound)

You may not qualify if:

• 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
• \. Randomized in another trial evaluating fostamatinib in the prior 30 days
• 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.

Sponsors & Collaborators

• NEAT ID Foundation: lead

Study Sites (21)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

Location

Hospital Federal dos Servidores do Estado

Rio de Janeiro, Brazil

Location

Instituto Nacional de Infectologia Evandro Chagas

Rio de Janeiro, Brazil

Location

University Hospital Bonn

Bonn, Germany

Location

University of Frankfurt

Frankfurt, Germany

Location

Ente Ospedaliero Ospedali Galliera

Genova, Italy

Location

San Paolo Hospital - ASST Santi Paolo e Carlo

Milan, Italy

Location

San Raffaele Turro Hospital

Milan, Italy

Location

University of Milan

Milan, Italy

Location

Worthwhile Clinical Trials (WWCT Lakeview Hospital)

Benoni, South Africa

Location

Clinical HIV Research Unit - Helen Joseph Hospital (WITS CHRU)

Johannesburg, South Africa

Location

Global Clinical Trials (Pty) Ltd

Pretoria, South Africa

Location

Hospital Clinic Barcelona

Barcelona, Villarroel, Spain

Location

Hospital General Universitario de Elche

Alicante, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Hospital Universitario Fundacion Alcorcon

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Universidad de Valladolid - Hospital Universitario Río Hortega

Valladolid, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, Spain

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

fostamatinib

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Early termination due to DSMB findings of extremely low likelihood of the intervention having a beneficial effect on the primary outcome led to a small number of participants enrolled by international sites and analysis being performed with data from all participants (International and US sites) in the fostamatinib arm of the ACTIV-4 Host Tissue study. Results for all participants in the fostamatinib arm of the ACTIV-4 Host Tissue study are recorded in Clinicaltrials.gov record NCT04924660.

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Research Organization (KC) Ltd

nectar@rokcservices.com

+44 (0) 7494 795 982

Study Officials

• Anton Pozniak, Prof

  NEAT ID

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Which study drug arm the participant enters will be known to the research sites and the participants, but assignment to active versus placebo will be blinded. The randomized assignment, concealed from the research team, will be transmitted to the site pharmacy, who will provide study medication. The participant, treating clinicians, study personnel (other than the unblinded statistician who will prepare closed DSMB interim reports), and outcome assessors will all remain blinded to group assignment until after the database is locked and blinded analysis is completed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly allocated in a two-step process: 1) The participant will first be randomized in an m:1 ratio to receive an active study drug or placebo, where m represents the number of study drug arms for which the participant is eligible. 2) The participant will then be randomly assigned with equal probability to one of the study drug arms. Participants will receive the corresponding study drug or matching placebo.

Study Record Dates

• First Submitted: October 21, 2022
• First Posted: October 25, 2022
• Study Start: October 27, 2022
• Primary Completion: December 14, 2023
• Study Completion: December 14, 2023
• Last Updated: May 2, 2025
• Results First Posted: November 5, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); ZA (3); BR (3); ES (9); DE (2)