No toxic reaction observed after 2-week repeated administration of recombinant whole human anti-SARS-CoV-2 monoclonal antibody 2811 injection in rhesus monkeys

ABSTRACT

OBJECTIVE To find out whether 2811 will cause toxic reactions in animals, and determine the safe dose of without any toxic reactions and the relationship between the dose, time of administration and results of the toxicity test. METHODS Thirty healthy rhesus monkeys were selected and randomly divided into 3 groups, 1 O in each group (half males and half females), namely, the solvent control group, 2811 100 and 400 mg* kg-1 groups, respectively. The solvent control group was iv given 0.9% sodium chloride injection, while the experimental groups were iv given 2811 100 and 400 mg* kg-1 , respectively, once every 6 days, 3 times in 2 weeks, and allowed to recover for 9 weeks after drug withdrawal. During the test, the body weight, food intakes, body temperatures, ophthalmology, blood pressure, electrocardiograms, blood routine, anticoagulation, blood biochemistry, electrolytes, urine, systemic anatomy, organ weight and coefficient were observed, while histopathology and immunology tests were performed. At the same time, the anti-drug antibody (ADA) and plasma concentrations were determined, and toxikinetic parameters were analyzed. RESULTS During the experiment, the observation of general symptoms, body mass, food intakes, body temperatures, ophthalmology, blood pressure, electrocardiograms, blood routine, anticoagulation, blood biochemistry, electrolytes, urine, organ weight and coefficient, histopathology and immunology of animals in each dose group showed no significant changes related to the tested animals. ADA was not detected in any of the groups. Plasma drug concentrations in 2B11 100 and 400 mg* kg-1 groups were basically consistent and proportional to the dose, so was the ratio of peak concentration and exposure. 2B11 injection showed linear kinetics in vivo. CONCLUSION Under the conditions set in this test, the 2-week repeated administration toxicity test of 2B11 in rhesus monkeys is safe, and no clinical adverse reactions are observed at the dose level of 400 mg*kg-1, which provides reference for the follow-up clinical study of 2B11. Copyright © 2022 Chinese Journal of Pharmacology and Toxicology. All rights reserved.