ACTIV-2 is a randomized, placebo-controlled platform designed to evaluate the safety and efficacy of multiple investigational agents for the treatment of non-hospitalized adults with COVID-19. Among other therapies, ACTIV-2 evaluated AZD7442, a combination of two human monoclonal antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061). Following initial studies that evaluated both a 300 mg intravenous dose and a 300 mg intramuscular dose of AZD744, ACTIV-2 evaluated an intramuscular 600 mg dose. This analysis evaluated the pharmacokinetics following administration in the thigh compared to the 300 mg intravenous dose.
This analysis included 84 of 110 participants in the intramuscular arm and 16 of 61 participants in the intravenous arm. Blood was collected prior to AZD7442 administration and at one, three, seven, and 14 days after administration. Across the two groups, 52 percent of participants were female; 87% identified as White, 8% as Black, 5% as multi-racial/other, and 49% as Hispanic/Latino.
Intramuscular administration of AZD7442 to the thigh produced sufficient serum concentrations for early treatment within 24 hours, with the highest concentrations at seven days. The total concentration over the first 14 days was higher in those who received 600 mg intramuscularly versus those who received 300 mg intravenously, although the initial concentrations after intravenous administration were higher until the three-day mark. Participants with higher weight or body mass index in both groups were more likely to have lower concentrations. Women appeared to have higher interparticipant variability in concentrations compared to men. There was less variability after administration to the thigh compared to data from the initial study in which it was administered intramuscularly to the gluteus muscle.
Route of administration is important to consider for anti-SARS-CoV-2 monoclonal antibodies. Administration to the thigh should be considered to provide consistent exposure and improve access to COVID-19 treatments, which otherwise are resource-intense to administer, and only accessible in certain healthcare facilities.
Rachel A Bender Ignacio, David A Wohl, Rosalin Arends, Venkatesh Pilla Reddy, Ying Mu, Arzhang Cyrus Javan, Michael D Hughes, Joseph J Eron, Judith S Currier, Davey Smith, Kara W Chew, Michael Gibbs, Courtney V Fletcher. Comparative Pharmacokinetics of Tixagevimab/Cilgavimab (AZD7442) Administered Intravenously Versus Intramuscularly in Symptomatic SARS-CoV-2 Infection. Clin Pharmacol Ther. 2022 Dec;112(6):1207-1213. doi: 10.1002/cpt.2706. Epub 2022 Jul 26.