ABSTRACT
Introduction: Equine hyperimmune serum (F(ab')2 fragments) has been widely used in Argentina in the last 100 years with satisfactory results and an acceptable safety profile in the treatment of accidents with poisonous animals such as snakes (bothrops, chrotalus, elapids) and arthropods (Loxosceles, Latrodectus, Phoneutria and Tityus). These antisera were developed by the National Institute for the production of Biologicals (ANLIS-Malbran) and distributed free of charge in public hospitals in the country. Objective(s): The aims of this study (NCT04913779) is to analyze the efficacy and safety of a passive immunotherapy strategy using hyperimmune equine serum known as Anti-SARS-CoV-2 elaborated by the National Institute for the Production of Biologicals (ANLISMalbran) as an addition to the standard therapeutic approach for hospitalized patients with COVID-19, in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Method(s): A randomized, double-blind controlled clinical study is carried out in 200 patients with COVID-19 requiring oxygen therapy in which the safety and efficacy of early use (72 hours from the onset of symptoms) of the research product is evaluated. The present work corresponds to a preliminary result of the safety and pharmacokinetic analysis in the first 20 patients included. Result(s): 20 initial patients (1:1 treatment: control ratio) were studied. The post-administration follow-up time was 28 days. The pharmacokinetic analysis shows that the research product presents an extracellular volume of distribution, with a median half-life of distribution was 6.3h (10-90% percentiles: 3.4-8.1 h) and half-life of elimination, 121h (10th-90th percentiles: 83-171 h). Neutralizing activity in plasma was correlated with drug concentration. Daily controls were carried out including physical examination, questioning in relation to symptoms presented, and blood extraction for routine laboratory control. No patient reported symptoms consistent with adverse reactions. Although some patients presented mild laboratory alterations (hepatogram, urea, creatinine), in all cases they were alterations that existed prior to the administration of the research product and that improved after treatment. Conclusion(s): Despite the small number of patients studied initially, and the possible masking of an adverse event due to the underlying disease (COVID-19), no significant adverse reactions were evidenced during treatment with the research product. There were no serious reactions and the pharmacokinetic characteristics appear to show a long-acting profile correlated with neutralizing activity in vitro.
ABSTRACT
Introduction: Equine hyperimmune serum (F(ab')2 fragments) has been widely used in Argentina in the last 100 years with satisfactory results and an acceptable safety profile in the treatment of accidents with poisonous animals such as snakes (bothrops, chrotalus, elapids) and arthropods (Loxosceles, Latrodectus, Phoneutria and Tityus). These antisera were developed by the National Institute for the production of Biologicals (ANLIS-Malbraín) and distributed free of charge in public hospitals in the country. Objective: The aims of this study (NCT04913779) is to analyze the efficacy and safety of a passive immunotherapy strategy using hyperimmune equine serum known as Anti-SARS-CoV-2 elaborated by the National Institute for the Production of Biologicals (ANLIS-Malbraín) as an addition to the standard therapeutic approach for hospitalized patients with COVID-19, in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: A randomized, double-blind controlled clinical study is carried out in 200 patients with COVID-19 requiring oxygen therapy in which the safety and efficacy of early use (72 hours from the onset of symptoms) of the research product is evaluated. The present work corresponds to a preliminary result of the safety and pharmacokinetic analysis in the first 20 patients included. Results: 20 initial patients (1:1 treatment: control ratio) were studied. The post-administration follow-up time was 28 days. The pharmacokinetic analysis shows that the research product presents an extracellular volume of distribution, with a median half-life of distribution was 6.3h (10-90% percentiles: 3.4-8.1 h) and half-life of elimination, 121h (10th-90th percentiles: 83-171 h). Neutralizing activity in plasma was correlated with drug concentration. Daily controls were carried out including physical examination, questioning in relation to symptoms presented, and blood extraction for routine laboratory control. No patient reported symptoms consistent with adverse reactions. Although some patients presented mild laboratory alterations (hepatogram, urea, creatinine), in all cases they were alterations that existed prior to the administration of the research product and that improved after treatment. Conclusion: Despite the small number of patients studied initially, and the possible masking of an adverse event due to the underlying disease (COVID-19), no significant adverse reactions were evidenced during treatment with the research product. There were no serious reactions and the pharmacokinetic characteristics appear to show a long-acting profile correlated with neutralizing activity in vitro.