Subcutaneous REGEN-COV Antibody Combination in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial

Abstract

Importance: Easy-to-administer antiviral treatments may be used to prevent progression from asymptomatic infection to COVID-19 and to reduce viral carriage.

Objective: Evaluate the efficacy and safety of subcutaneous casirivimab and imdevimab antibody combination (REGEN-COV) to prevent progression from early asymptomatic SARS-CoV-2 infection to COVID-19.

Design: Randomized, double-blind, placebo-controlled, phase 3 study that enrolled asymptomatic close contacts living with a SARS-CoV-2-infected household member (index case). Participants who were SARS-CoV-2 RT-qPCR-positive at baseline were included in the analysis reported here.

Setting: Multicenter trial conducted at 112 sites in the United States, Romania, and Moldova.

Participants: Asymptomatic individuals ≥12 years of age were eligible if identified within 96 hours of collection of the index case's positive SARS-CoV-2 test sample.

Interventions: A total of 314 asymptomatic, SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact were randomized 1:1 to receive a single dose of subcutaneous REGEN-COV 1200mg (n=158) or placebo (n=156).

Main outcomes and measures: The primary endpoint was the proportion of participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy endpoints were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL). Safety was assessed in all treated participants.

Results: Subcutaneous REGEN-COV 1200mg significantly prevented progression from asymptomatic to symptomatic disease compared with placebo (31.5% relative risk reduction; 29/100 [29.0%] vs 44/104 [42.3%], respectively; P=.0380). REGEN-COV reduced the overall population burden of high-viral load weeks (39.7% reduction vs placebo; 48 vs 82 total weeks; P=.0010) and of symptomatic weeks (45.3% reduction vs placebo; 89.6 vs 170.3 total weeks; P=.0273), the latter corresponding to an approximately 5.6-day reduction in symptom duration per symptomatic participant. Six placebo-treated participants had a COVID-19-related hospitalization or ER visit versus none for those receiving REGEN-COV. The proportion of participants receiving placebo who had ≥1 treatment-emergent adverse events was 48.1% compared with 33.5% for those receiving REGEN-COV, including events related (39.7% vs 25.8%, respectively) or not related (16.0% vs 11.0%, respectively) to COVID-19.

Conclusions and relevance: Subcutaneous REGEN-COV 1200mg prevented progression from asymptomatic SARS-CoV-2 infection to COVID-19, reduced the duration of high viral load and symptoms, and was well tolerated.

Trial registration: ClinicalTrials.gov Identifier, NCT04452318.

Figures

Figure 1.. Prevention of Symptomatic SARS-CoV-2 Infection With REGEN-COV.

A, Time to first symptom with an onset within 14 days of a positive RT-qPCR at baseline or during the efficacy assessment period.a B, Total weeks of symptomatic SARS-CoV-2 infectionb by arm.a C, Mean number of days of symptomatic SARS-CoV-2 infectionb per symptomatic participant.a aSeronegative modified full analysis set-B. bWithin 14 days of a positive RT-qPCR at baseline or during the efficacy assessment period. Abbreviations: RT-qPCR, reverse transcriptase quantitative polymerase chain reaction; SD, standard deviation.

Figure 2.. Reduction in SARS-CoV-2 Viral Load With REGEN-COV.

A, Viral load over time.a B, Mean number of weeks of high viral load.a,b C, Percentage of participants with high viral load by duration.a,b D, Peak viral load post-baseline during the EAP.a,c aSeronegative modified full analysis set-B. Only non-missing available nasopharyngeal swab viral load data are used for the analysis of viral load endpoints. Only participants with at least one post-baseline viral load data point (in nasopharyngeal swab samples) are included in the analysis. bHigh viral load was defined as >4 log10 copies per milliliter. cLines in the boxes represent the median; large, bolded dots in the boxes represent the mean; bottom and top of boxes represent quartiles 1 (25th percentile) and 3 (75th percentile), respectively; whiskers represent the maximum and minimum. Abbreviations: EAP, efficacy assessment period; SD, standard deviation; SE, standard error.