Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study

Abstract

BackgroundImmune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease.MethodsThirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication.ResultsWe observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events.ConclusionsThis pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.

Higher versus lower dose corticosteroids for severe to critical COVID-19: A systematic review and dose-response meta-analysis

“…Seven trials randomized patients to corticosteroid with cumulative doses of ≤60 mg dexamethasone equivalent or standard care or placebo, eight trials randomized patients to with cumulative dose of >60 mg dexamethasone equivalent or standard care or placebo, and six trials compared head-to-head corticosteroid doses (4,(40)(41)(42)48). Table 1 presents more details on trial characteristics (3,4,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(51)(52)(53).…”

TriTECM: A tetrafunctional T-cell engaging antibody with built-in risk mitigation of cytokine release syndrome

“…For CD3ϵ-engagement, the fully human monoclonal antibody foralumab (NI0401, abbreviated as αCD3ϵ) was considered ( 71 , 72 ), from which a single-chain variable fragment (scFv) was derived. Clinical investigations have been performed using different formulations of foralumab for several indications, including non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus, primary and secondary multiple sclerosis, and more recently for COVID-19 infections ( 71 , 73 ).…”

“…Clinical investigations have been performed using different formulations of foralumab for several indications, including non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus, primary and secondary multiple sclerosis, and more recently for COVID-19 infections ( 71 , 73 ). According to a reported study by Moreira et al., nasal administration of foralumab in a pilot study using patients with mild to moderate COVID-19 disease severity led to no CRS and lowered IL-6 blood levels 10 days after administration ( 72 ). For this proof-of-concept study, the anti-CD3 scFv was used as a CD3-based T-cell engager.…”

Higher- versus Lower-Dose Corticosteroids for Severe to Critical COVID-19: A Systematic Review and Dose–Response Meta-analysis

“…Seven trials randomized patients to corticosteroid with ≤6 mg dexamethasone equivalent/day for 10 days or standard care or placebo, eight trials randomized patients to with >=6 mg/day for 10 days of dexamethasone equivalent or standard care or placebo, and seven trials compared head-to-head corticosteroid doses (4, 43-45, 49, 51, 54). Table 1 presents more details on trial characteristics (3,4,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(54)(55)(56)(57) and eTable 3 presents more details on co-interventions and vaccination status.…”