IMPORTANCE Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19. OBJECTIVE To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebowere enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. INTERVENTIONS Patientswere randomized to receive a single infusion of bamlanivimab (700mg [n = 101], 2800mg [n = 107], or 7000mg [n = 101]), the combination treatment (2800mg of bamlanivimab and 2800mg of etesevimab [n = 112]), or placebo (n = 156). MAIN OUTCOMES AND MEASURES The primary end pointwas change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29). RESULTS Among the 577 patientswhowere randomized and received an infusion (mean age,44.7 [SD, 15.7] years; 315 [54.6%]women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11was -3.72 for 700mg, -4.08for2800mg, -3.49for7000mg,-4.37forcombinationtreatment,and-3.80forplacebo.Comparedwithplacebo, the differences in thechangein log viral load atday 11were0.09(95%CI,-0.35 to0.52;P = .69)for 700mg, -0.27 (95%CI, -0.71 to0.16; P = .21) for2800mg,0.31 (95%CI, -0.13 to0.76; P = .16) for 7000mg, and -0.57 (95%CI, -1.00to -0.14; P = .01) for combination treatment.Among the secondary outcome measures, differences between each treatment group vs the placebo group werestatistically significant for10of84endpoints.TheproportionofpatientswithCOVID-19-related hospitalizationsorEDvisitswas5.8%(9events)forplacebo, 1.0%(1event)for700mg,1.9%(2events) for2800mg, 2.0%(2 events) for 7000mg, and0.9%(1 event) for combination treatment. Immediatehypersensitivity reactionswere reported in9patients (6 bamlanivimab,2combination treatment, and 1 placebo).Nodeaths occurred during the study treatment. CONCLUSIONS AND RELEVANCE Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point.
|Original language||English (US)|
|Number of pages||13|
|Journal||JAMA - Journal of the American Medical Association|
|State||Published - Feb 16 2021|
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