Dataset Information

Subcutaneous REGEN-COV Antibody Combination in Early SARS-CoV-2 Infection.

ABSTRACT:

Background

Casirivimab and imdevimab administered together (REGEN-COV™) markedly reduces the risk of hospitalization or death in high-risk, symptomatic individuals with COVID-19. Here, we report phase 3 results of early treatment of asymptomatic, SARS-CoV-2-positive adults and adolescents with subcutaneous REGEN-COV.

Methods

Individuals ≥12 years of age were eligible if identified within 96 hours of a household contact being diagnosed as SARS-CoV-2-positive; 314 were randomized 1:1 to receive subcutaneous REGEN-COV 1200mg or placebo. The primary endpoint was the proportion of infected participants without evidence of prior immunity (i.e., SARS-CoV-2-RT-qPCR-positive/seronegative) who subsequently developed symptomatic Covid-19 during a 28-day efficacy assessment period.

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=0.0380). REGEN-COV also reduced the overall population burden of high viral load weeks (39.7% reduction vs. placebo; 48 vs. 82 total weeks; P=0.0010) and of symptomatic weeks (45.3% reduction vs. placebo; 89.6 vs. 170.3 total weeks; P=0.0273), the latter corresponding to an approximately 5.6-day reduction 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 to 33.5% for those receiving REGEN-COV, including Covid-19-related (39.7% vs. 25.8%, respectively) or non-Covid-19-related (16.0% vs. 11.0%, respectively) events.

Conclusions

Subcutaneous REGEN-COV 1200mg prevented progression from asymptomatic to symptomatic infection, reduced the duration of high viral load and symptoms, and was well tolerated.(ClinicalTrials.gov number, NCT04452318.).

SUBMITTER: O'Brien MP

PROVIDER: S-EPMC8219113 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

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

O'Brien Meagan P MP Forleo-Neto Eduardo E Sarkar Neena N Isa Flonza F Hou Peijie P Chan Kuo-Chen KC Musser Bret J BJ Bar Katharine J KJ Barnabas Ruanne V RV Barouch Dan H DH Cohen Myron S MS Hurt Christopher B CB Burwen Dale R DR Marovich Mary A MA Brown Elizabeth R ER Heirman Ingeborg I Davis John D JD Turner Kenneth C KC Ramesh Divya D Mahmood Adnan A Hooper Andrea T AT Hamilton Jennifer D JD Kim Yunji Y Purcell Lisa A LA Baum Alina A Kyratsous Christos A CA Krainson James J Perez-Perez Richard R Mohseni Rizwana R Kowal Bari B DiCioccio A Thomas AT Stahl Neil N Lipsich Leah L Braunstein Ned N Herman Gary G Yancopoulos George D GD Weinreich David M DM

medRxiv : the preprint server for health sciences 20210918

<h4>Importance</h4>Easy-to-administer antiviral treatments may be used to prevent progression from asymptomatic infection to COVID-19 and to reduce viral carriage.<h4>Objective</h4>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.<h4>Design</h4>Randomized, double-blind, placebo-controlled, phase 3 study that enrolled asymptomatic close contacts living with a ...[more]

PMID: 34159343

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Project description:BackgroundREGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown.MethodsWe randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity).ResultsSymptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted.ConclusionsSubcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.).

Project description:ImportanceEasy-to-administer anti-SARS-CoV-2 treatments may be used to prevent progression from asymptomatic infection to symptomatic disease and to reduce viral carriage.ObjectiveTo evaluate the effect of combination subcutaneous casirivimab and imdevimab on progression from early asymptomatic SARS-CoV-2 infection to symptomatic COVID-19.Design, setting, and participantsRandomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2-infected index case at 112 sites in the US, Romania, and Moldova enrolled July 13, 2020-January 28, 2021; follow-up ended March 11, 2021. Asymptomatic individuals (aged ≥12 years) were eligible if identified within 96 hours of index case positive test collection. Results from 314 individuals positive on SARS-CoV-2 reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) testing are reported.InterventionsIndividuals were randomized 1:1 to receive 1 dose of subcutaneous casirivimab and imdevimab, 1200 mg (600 mg of each; n = 158), or placebo (n = 156).Main outcomes and measuresThe primary end point was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy end points were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL).ResultsAmong 314 randomized participants (mean age, 41.0 years; 51.6% women), 310 (99.7%) completed the efficacy assessment period; 204 were asymptomatic and seronegative at baseline and included in the primary efficacy analysis. Subcutaneous casirivimab and imdevimab, 1200 mg, significantly prevented progression to symptomatic disease (29/100 [29.0%] vs 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% CI, 0.30-0.97]; P = .04; absolute risk difference, -13.3% [95% CI, -26.3% to -0.3%]). Casirivimab and imdevimab reduced the number of symptomatic weeks per 1000 participants (895.7 weeks vs 1637.4 weeks with placebo; P = .03), an approximately 5.6-day reduction in symptom duration per symptomatic participant. Treatment with casirivimab and imdevimab also reduced the number of high viral load weeks per 1000 participants (489.8 weeks vs 811.9 weeks with placebo; P = .001). The proportion of participants receiving casirivimab and imdevimab who had 1 or more treatment-emergent adverse event was 33.5% vs 48.1% for placebo, including events related (25.8% vs 39.7%) or not related (11.0% vs 16.0%) to COVID-19.Conclusions and relevanceAmong asymptomatic SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days.Trial registrationClinicalTrials.gov Identifier: NCT04452318.

Project description:BackgroundIn the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.MethodsIn the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated.ResultsCovid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.ConclusionsREGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Project description:BackgroundIn vitro studies suggesting that REGEN-COV (casirivimab plus imdevimab monoclonal antibodies) had poor efficacy against Omicron-variant SARS-CoV-2 infection led to amendment of REGEN-COV's Emergency Use Authorization to recommend use only in regions without high Omicron prevalence. REGEN-COV's relative clinical effectiveness for Omicron is unknown.Methods and findingsWe conducted a retrospective cohort study of non-hospitalized adults who tested positive for SARS-CoV-2 by polymerase chain reaction at the University of Miami Health System from July 19 -November 21, 2021 (Delta period) and December 6, 2021 -January 7, 2022 (Omicron period). Subjects were stratified be REGEN-COV receipt within 72h of test positivity and by time period of infection. We constructed multivariable logistic regression models to assess the differential association of REGEN-COV receipt with hospitalization within 30 days (primary outcome) and ED presentation; all models included three exposure terms (REGEN-COV receipt, Omicron vs Delta period, interaction of REGEN-COV with time period) and potential confounders (vaccination status, vaccine boosting, cancer diagnosis). Our cohort consisted of 2,083 adults in the Delta period (213 [10.2%] received REGEN-COV) and 4,201 in the Omicron period (156 [3.7%] received REGEN-COV). Hospitalization was less common during the Omicron period than during Delta (0.9% vs 1.7%, p = 0.78) and more common for patients receiving REGEN-COV than not (5.7% vs 0.9%, p<0.001). After adjustment, we found no differential association of REGEN-COV use during Omicron vs Delta with hospitalization within 30d (adjusted odds ratio [95% confidence interval] for the interaction term: 2.31 [0.76-6.92], p = 0.13). Similarly, we found no differential association for hospitalization within 15d (2.45 [0.63-9.59], p = 0.20) or emergency department presentation within 30d (1.43 [0.57-3.51], p = 0.40) or within 15d (1.79 [0.65-4.82], p = 0.30).ConclusionsWithin the limitations of this study's power to detect a difference, we identified no differential effectiveness of REGEN-COV in the context of Omicron vs Delta SARS-CoV-2 infection.