Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial

Abstract

Importance: Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19.

Objective: To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities.

Design, setting, and participants: Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57.

Interventions: Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587).

Main outcomes and measures: The primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection.

Results: The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%; odds ratio, 0.43 [95% CI, 0.28-0.68]; P < .001; absolute risk difference, -6.6 [95% CI, -10.7 to -2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo).

Conclusions and relevance: Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT04497987.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Nirula, Custer, Adams, Schade, Dabora, Knorr, Price, Sabo, Tuttle, Klekotka, Shen, and Skovronsky and Mr Van Naarden are all employees and shareholders of Eli Lilly and Co. Dr Mulligan reported receiving funding from Pfizer and Sanofi and personal fees from Pfizer. Dr Wohl reported receiving funding from Gilead Sciences, Merck, and ViiV Healthcare and personal fees from Gilead Sciences, Janssen, ViiV Healthcare, and Merck. Dr Frank reported receiving funding from Sanofi Pasteur and Janssen and advisory board/consultation fees from Gilead Sciences and ViiV Healthcare. Dr Fichtenbaum reported receiving grants from Regeneron and Ansun. Dr Ramirez reported receiving grants from Johnson & Johnson. Dr Brown reported receiving grants from the Bill and Melinda Gates Foundation and personal fees from Merck. No other disclosures were reported.

Figures

Figure 1.. Flow of Participants Through the BLAZE-2 Randomized Clinical Trial

RT-PCR indicates reverse transcriptase–polymerase chain reaction. aA majority of the 95 screening failures were due to a lack of venous access sufficient to allow intravenous infusions and blood sampling per protocol (45 participants) or due to a serious concomitant systemic disease, condition, or disorder that in the opinion of investigators should preclude participation (34 participants), as described in sections 5.1 and 5.2 of the trial protocol (Supplement 1). bOne participant provided signed consent but did not return for infusion, and for 1 participant, infusion nurses were unable to secure intravenous access despite multiple attempts. cThe treatment population will be reported on in a future publication.

Figure 2.. Time From Infusion to Development of Mild or Worse COVID-19 With Bamlanivimab vs Placebo Among Resident and Staff Participants

Participants were negative at baseline for SARS-CoV-2 by reverse transcriptase–polymerase chain reaction and serology. More than 95% of participants were followed up beyond day 57. Similar data for other subgroups are shown in eFigure 1 in Supplement 2.

Figure 3.. Time From Infusion to Detection of SARS-CoV-2 by RT-PCR With Bamlanivimab vs Placebo and Viral Load in Participants Who Tested Positive for SARS-CoV-2 During the Study

A and B, Kaplan-Meier curves for time from infusion to detection of SARS-CoV-2 by reverse transcriptase–polymerase chain reaction (RT-PCR) with bamlanivimab vs placebo among resident and staff participants. Participants were negative at baseline for SARS-CoV-2 by RT-PCR and serology. More than 95% of participants were followed up beyond day 57. Similar data for other subgroups are shown in eFigure 2B in Supplement 2. C and D, Spaghetti plots for log10 viral load over time for resident and staff participants. Participants were negative at baseline for SARS-CoV-2 by RT-PCR and serology. Participants with at least 1 positive postbaseline SARS-CoV-2 RT-PCR test result: bamlanivimab group, n = 23 residents and n = 62 staff; placebo group, n = 44 residents and n = 68 staff. Time 0 represents the time of a participant’s first positive RT-PCR test result. Each line represents a participant. E, Box plot for log10 viral load over time for participants with at least 1 positive postbaseline SARS-CoV-2 RT-PCR test result. Time 0 represents the time of a participant’s first positive RT-PCR test result. Box tops and bottoms indicate interquartile ranges; solid horizontal bars, medians; hollow squares, means; whiskers, lowest and highest observations within 1.5 interquartile ranges of the first and third quartiles; and dots, outliers. In the later weeks, the 25th, 50th, and 75th percentiles are coincident, so the boxes appear as solid horizontal bars.