Infect Dis Ther . Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Fin

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1. Infect Dis Ther
4. . 2024 Feb 25.
5. doi: 10.1007/s40121-024-00931-4. Online ahead of print. Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial

F D Richard Hobbs[SUP] 1 2 [/SUP], Hugh Montgomery[SUP] 3 [/SUP], Francisco Padilla[SUP] 4 [/SUP], Jesus Abraham Simón-Campos[SUP] 5 [/SUP], Douglas Arbetter[SUP] 6 [/SUP], Seth Seegobin[SUP] 7 [/SUP], Alexandre Kiazand[SUP] 8 [/SUP], Katie Streicher[SUP] 9 [/SUP], Nuria Martinez-Alier[SUP] 7 [/SUP], Taylor S Cohen[SUP] 9 [/SUP], Mark T Esser[SUP] 10 [/SUP]



Affiliations

• PMID: 38403865
• DOI: 10.1007/s40121-024-00931-4

Abstract

Introduction: In the phase 3 TACKLE study, outpatient treatment with AZD7442 (tixagevimab/cilgavimab) was well tolerated and significantly reduced progression to severe disease or death through day 29 in adults with mild-to-moderate coronavirus disease 2019 (COVID-19) at the primary analysis. Here, we report data from the final analysis of the TACKLE study, performed after approximately 15 months' follow-up.
Methods: Eligible participants were randomized 1:1 and dosed within 7 days of symptom onset with 600 mg intramuscular AZD7442 (n = 456; 300 mg tixagevimab/300 mg cilgavimab) or placebo (n = 454).
Results: Severe COVID-19 or death through day 29 occurred in 4.4% and 8.8% of participants who received AZD7442 or placebo, a relative risk reduction (RRR) of 50.4% [95% confidence interval (CI) 14.4, 71.3; p = 0.0096]; among participants dosed within 5 days of symptom onset, the RRR was 66.9% (95% CI 31.1, 84.1; p = 0.002). Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 occurred in 5.0% of participants receiving AZD7442 versus 9.7% receiving placebo, an RRR of 49.2% (95% CI 14.7, 69.8; p = 0.009). Adverse events occurred in 55.5% and 55.9% of participants who received AZD7442 or placebo, respectively, and were mostly mild or moderate in severity. Serious adverse events occurred in 10.2% and 14.4% of participants who received AZD7442 or placebo, respectively, and deaths occurred in 1.8% of participants in both groups. Serum concentration-time profiles recorded over 457 days were similar for AZD7442, tixagevimab, and cilgavimab, and were consistent with the extended half-life reported for AZD7442 (approx. 90 days).
Conclusions: AZD7442 reduced the risk of progression to severe COVID-19, hospitalization, and death, was well tolerated through 15 months, and exhibited predictable pharmacokinetics in outpatients with mild-to-moderate COVID-19. These data support the long-term safety of using long-acting monoclonal antibodies to treat COVID-19.
Trial registration: Clinicaltrials.gov, NCT04723394. ( https://clinicaltrials.gov/study/NCT04723394 .

Keywords: COVID-19; Cilgavimab; Clinical trial; Monoclonal antibody; Tixagevimab.

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