RBD-Specific Polyclonal F(ab´) ₂ Fragments of Equine Antibodies in Patients with Moderate to Severe COVID-19 Disease: A Randomized, Double-Blind, Placebo-Controlled, Adaptive Phase 2/3 Clinical Trial

Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies

“…To evaluate the safety and biodistribution of repeated administrations of CoviFab, a dose of 4 mg/kg was administered to the treated animals via intravenous tail-vein injection (5 ml/kg) at time 0 and at 48 h. This dose and application scheme coincide with the ones used in the clinical trial, based on the therapeutic dose of similar products ( Lopardo et al, 2021 ). Control animals received sterile sodium chloride solution (0.9% w / v in water).…”

“…This method has been previously developed and validated according to FDA guidelines (Guidance for Industry: Bioanalytical Method Validation, FDA, 2018 ) to determine the concentration of equine F(ab′)2 in serum samples from different species including mice ( Hiriart et al, 2019 ; Lopardo et al, 2021 ). The method consisted of sandwich ELISA, in which the samples were incubated in a plate coated with an anti-equine F(ab′)2 antibody (LS-C60458, LS Bio, USA), and revealed by the addition of an anti-equine immunoglobulins antibody conjugated with peroxidase (SC-2448, Santa Cruz USA).…”

“…In this sense, F(ab′)2 fragments retain the bivalent binding ability of IgG antibodies while avoiding the potential ADE consequence, due to the lack of the Fc region ( Wu et al, 2020 ; Lee et al, 2020 ). Therefore, in patients with a severe disease, these differences might explain why CoviFab, and not CP therapy, might be associated with better outcomes in well controlled clinical trials ( Simonovich et al, 2021 ; Lopardo et al, 2021 ).…”

“…The NEAST therapy has successfully passed preclinical and phase 1 analysis, showing an adequate safety and pharmacokinetics profile. Its positive evaluation enabled the initiation of a 2/3-phase clinical trial in the paediatric population, which is currently ongoing ( http://www.clinicaltrials.gov , NCT04132375 ) ( Lopardo et al, 2021 ) and, therefore, it is in the process of registration in several regulatory agencies such as the National Administration of Drugs, Food, and Medical Technology (ANMAT) and European Medicines Agency (EMA).…”

“…Taking into account this safety and pharmacokinetic background, and given the similarity of the F(ab′)2 molecules, the Argentine regulatory authorities ANMAT authorised a 2/3-phase clinical trial ( http://www.clinicaltrials.gov , NCT04494984 ) for CoviFab and its registration and emergency approval ( Lopardo et al, 2021 ).…”