Phase 3 Trial of Fostamatinib for the Treatment of COVID-19: Repurposing an Immunomodulatory Drug Previously Approved for Immune Thrombocytopenia
Open Forum Infectious Diseases
; 8(SUPPL 1):S382-S383, 2021.
Article
in English
| EMBASE | ID: covidwho-1746437
ABSTRACT
Background. Key pathologies in severe COVID-19 include immune cell activation, inflammatory cytokine release, and neutrophil extracellular trap release (NETosis), which are mediated by spleen tyrosine kinase (SYK) (Figure 1). Fostamatinib, an oral SYK inhibitor approved for chronic immune thrombocytopenia, has shown activity in vitro using plasma from patients with severe COVID-19, by abrogating the hyperimmune response triggered by anti-spike IgG;1 inhibiting hyperactivation in platelets;2 and blocking NETosis in neutrophils.3 R406, active metabolite of fostamatinib, protected against LPS-induced acute lung injury and thrombosis in mice.4,5 In clinical studies, fostamatinib reduced IL-6 in patients with rheumatoid arthritis.6 Therefore, a phase 2 study (NCT04579393) evaluated fostamatinib vs. placebo plus standard of care (SOC) in 59 hospitalized COVID-19 patients (manuscript pending). We initiated a phase 3 clinical study (NCT04629703) of fostamatinib for the treatment of COVID-19. Methods. A double-blind, randomized, placebo-controlled, adaptive design, multi-center, Phase 3 study (NCT04629703) is underway to evaluate the safety and efficacy of fostamatinib in 308 adult patients with COVID-19 (Figure 2). Hospitalized patients without respiratory failure (with or without supplemental oxygen) were included. Patients with ARDS or using extracorporeal membrane oxygenation (ECMO) were excluded. Patients will receive fostamatinib 150 mg BID or placebo for 14 days;both arms receive SOC. The primary outcome will be progression to severe/critical disease (worsening in clinical status score on the 8-point ordinal scale) within 29 days of the first dose of study drug. Fostamatinib is investigational for COVID-19. Results. Blinded update of trial in progress as of 28 April 2021. 12 patients have been randomized in North and South America. The clinical status score at Baseline was 5 (Hospitalized, requiring supplemental oxygen) in all 12 patients. Five patients had 8 adverse events (AE) (Fig 3). One AE (PE) was serious and is resolving. No deaths have been reported. At least two patients have been discharged (Day 5, Day 13) with continued dosing at home. Conclusion. Fostamatinib has the potential to provide a treatment option for the hyperimmune complications of COVID-19.
endogenous compound; fostamatinib; immunoglobulin G; immunomodulating agent; interleukin 6; oxygen; placebo; adult; adult respiratory distress syndrome; animal cell; animal experiment; animal model; animal tissue; autoimmune thrombocytopenia; complication; conference abstract; coronavirus disease 2019; double blind procedure; drug safety; drug therapy; extracorporeal oxygenation; health care quality; hospital discharge; hospital patient; human; in vitro study; lipopolysaccharide-induced acute lung injury; male; mouse; neutrophil; nonhuman; outcome assessment; phase 2 clinical trial; phase 3 clinical trial; respiratory failure; rheumatoid arthritis; single blind procedure; South America; spike; thrombocyte; thrombosis
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Randomized controlled trials
Language:
English
Journal:
Open Forum Infectious Diseases
Year:
2021
Document Type:
Article
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