Among patients hospitalized with COVID-19, a single infusion of tixagevimab-cilgavimab, which is added to background treatment with remdesivir and other standard care, resulted in 30% lower mortality compared with standard of care treatment, but did not reduce the time to occurrence of sustained recovery. These were among phase 3 clinical trial findings published in The Lancet Respiratory Medicine.
In previous studies of nonhospitalized individuals with COVID-19, tixagevimab–cilgavimab prevented symptomatic COVID-19 when administered prophylactically, reduced hospitalizations by more than 50% in recently infected individuals, and maintained antiviral activity against omicron variants.
The current randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT04501978) focused on hospitalized patients, comparing treatment with tixagevimab-cilgavimab vs placebo in adult inpatients with confirmed SARS-CoV-2 infection and symptoms for at least 12 days who were receiving remdesivir and other standard care. The study was conducted at 81 sites in the United States, Europe, Uganda, and Singapore between February 10, 2021, and September 30, 2021. A total of 1455 patients were randomly assigned to the study, with 1417 individuals in the primary modified intention-to-treat population receiving an infusion of either tixagevimab-cilgavimab (n=710) or placebo (n=707).
The primary study outcome was time from randomization to sustained clinical recovery up to day 90, with “sustained recovery” defined as return to home for 14 consecutive days. Key secondary outcomes included all-cause mortality up to day 90, as well as a composite of sustained recovery and mortality up to day 90. Additional secondary outcomes included a 7-category pulmonary ordinal outcome scale; a 7-category pulmonary-plus ordinal outcome scale; time to discharge from the index hospitalization; and a composite of safety outcomes through days 5, 28, and 90.
Results of the study showed that the estimated cumulative incidence of sustained recovery was 89% with tixagevimab-cilgavimab vs 86% with placebo at day 90 in the full cohort (recovery rate ratio [RRR], 108; 95% CI, 0.97-1.20; P =.21). Findings were similar in the seronegative subgroup (RRR, 1.14; 95% CI, 0.97-1.34; P =.13).
Additionally, the mortality rate was lower in the tixagevimab-cilgavimab arm compared with the placebo arm (9% vs 12%, respectively; hazard ratio [HR], 0.70; 95% CI, 0.50-0.97; P =.32). The composite safety outcome was reported in 25% of tixagevimab-cilgavimab–treated participants vs 30% of placebo-treated participants (HR, 0.83;
95% CI, 0.68-1.01; P =.59). Serious adverse events occurred in 5% of participants in both of the groups.
A major limitation of the current study was the conclusion of enrollment prior to the emergence of the omicron variant. Further, because only a minority of the participants were fully vaccinated, it is difficult to extrapolate study results to vaccinated and/or boosted patients.
The investigators concluded that although tixagevimab-cilgavimab treatment did not reduce time to the primary outcome, the mortality reduction associated with use of this therapy in combination with standard of care suggest it may be a useful for patients hospitalized with COVID-19.
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. Published online July 8, 2022. doi:10.1016/S2213-2600(22)00215-6