Prophylactic Use of Tixagevimab-Cilgavimab After COVID-19 Exposure Is Limited

Tixagevimab-cilgavimab was safe as post-exposure prophylaxis against COVID-19 infection but was not associated with reduced risk for symptomatic infection.

Results of a phase 3 trial showed no evidence that post-exposure prophylaxis with tixagevimab and cilgavimab prevents symptomatic COVID-19 infection. These study findings were published in Clinical Infectious Diseases.

The COVID-19 Study to Optimally Reduce Morbidity in Care Homes and Sites with Enhanced Risk (STORM CHASER) is an ongoing, 15-month, randomized, double-blind, placebo-controlled trial. Individuals (N=1121) across 59 sites in the United States and United Kingdom who were potentially exposed to an individual with symptomatic or asymptomatic COVID-19 infection in a high-exposure risk setting were randomly assigned in a 2:1 fashion to receive either 1 intramuscular injection of AZD7442 (tixagevimab 150 mg plus cilgavimab 150 mg; n=749) or placebo (n=372). The study outcomes were treatment safety and real-time polymerase chain reaction (RT-PCR)-positivity for COVID-19 infection before day 183.

Among patients included in the study, the mean (SD) age was 46.4 (15.9) years, 49.4% were women, 84.1% were White, 65.7% had at least 1 COVID-19-related risk factor, 8.5% were positive for SARS-CoV-2 nucleocapsid antibodies, and 4.3% were RT-PCR positive for SARS-CoV-2 infection at baseline.

Among patients in the intervention cohort, the geometric mean serum concentration of AZD7442 was 18.7 µg/mL at day 8 and 24.9 µg/mL at day 58.

Patients in the intervention and control cohorts reported an adverse event rate of 21.6% and 29.8%, respectively. Among the AZD7442 recipients, 0.9% of AEs were severe, 0.1% were potentially life-threatening, and 4.3% were medically attended. No AEs led to study withdrawal or death.

Symptomatic COVID-19 infection occurred among 3.1% of patients in the intervention cohort and among 4.6% of those in the placebo cohort, indicating no association between AZD7442 and a decrease risk for symptomatic COVID-19 infection (relative risk reduction [RRR], 33.3%; 95% CI, -25.9% to 64.7%; P =.21).

Findings among participants from high exposure risk environments who were SARS-CoV-2 RT-PCR-negative or missing RT-PCR result at baseline support a role for AZD7442 in prevention of symptomatic COVID-19.

Of patients with negative or missing RT-PCR results at baseline, AZD7442 was associated with a decreased risk for symptomatic COVID-19 infection (RRR, 73.2%; 95% CI, 27.1%-90.1%). No other significant subgroup effects were observed.

There was 1 placebo recipient who developed severe COVID-19 infection, thus no formal analysis was performed.

This study may have been limited by allowing study inclusion up to 8 days after the potential exposure event, resulting in a high number of COVID-19-positive patients at baseline.

“Findings among participants from high exposure risk environments who were SARS-CoV-2 RT-PCR-negative or missing RT-PCR result at baseline support a role for AZD7442 in prevention of symptomatic COVID-19,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

References:

Levin MJ, Ustianowski A, Thomas S, et al. AZD7442 (Tixagevimab/Cilgavimab) for Post-Exposure Prophylaxis of Symptomatic Coronavirus Disease 2019. Clin Infect Dis. Published online November 22, 2022. doi:10.1093/cid/ciac899