1924. 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 1:1 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.