Outpatient Treatment With the SARS-CoV-2-Neutralizing Antibody Combination AZD7442 (Tixagevimab/Cilgavimab) for Preventing COVID-19 Hospitalizations in the Phase 3 TACKLE Trial

ABSTRACT

Background. Outpatient treatment with SARS-CoV-2-neutralizing antibody combination AZD7442 (tixagevimab/cilgavimab) in adults with mild to moderate COVID-19 significantly reduced progression to severe disease or death through Day 29 and was well-tolerated in the Phase 3 TACKLE study primary analysis (NCT04723394). AZD7442 administered earlier in the disease course leads to more favorable outcomes and has the potential to prevent COVID-19 hospitalizations and reduce hospital burden. We report key secondary efficacy results with longerterm safety data from TACKLE over 6 months. Methods. In TACKLE, non-hospitalized adults with mild to moderate COVID-19 were randomized 11 and dosed <=7 days from symptom onset with a single 600-mg AZD7442 dose (2 consecutive intramuscular injections, 300 mg of each antibody;n=452) or placebo (n=451). The key secondary endpoint was death from any cause or hospitalization for COVID-19 complications or sequelae through Day 169, analyzed using a Cochran-Mantel-Haenszel test stratified by time from symptom onset and risk of severe COVID-19 progression. Results. Death from any cause or hospitalization for COVID-19 complications or sequalae occurred in 20 (5.0%) versus 40 (9.8%) participants receiving AZD7442 versus placebo, respectively, translating to a relative risk reduction (RRR) of 49.1% (95% confidence interval [CI] 14.5-69.7) versus placebo (P=0.009). A sensitivity analysis excluding participants who were unblinded prior to Day 169 for consideration of vaccination yielded a similar RRR of 50.7% (95% CI 17.5-70.5;P=0.006). For baseline seronegative participants, an RRR of 58.6% (95% CI 27.6-76.4;P=0.001) was observed. The median (range) safety follow-up was 170 (1-330) days with AZD7442 and 170 (1-326) days with placebo. Adverse events occurred in 38.5% of AZD7442 participants and 43.5% of placebo participants, and were mostly mild to moderate. Conclusion. A single 600-mg AZD7442 dose demonstrated statistically significant protection against death from any cause or hospitalization for COVID-19 through 6 months, and was well-tolerated. These data provide further support of AZD7442 in the COVID-19 outpatient treatment setting, with potential to reduce hospital burden.