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Clinical Trial
. 2021 Jan 21;384(3):229-237.
doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28.

SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19

Peter Chen  1 , Ajay Nirula  1 , Barry Heller  1 , Robert L Gottlieb  1 , Joseph Boscia  1 , Jason Morris  1 , Gregory Huhn  1 , Jose Cardona  1 , Bharat Mocherla  1 , Valentina Stosor  1 , Imad Shawa  1 , Andrew C Adams  1 , Jacob Van Naarden  1 , Kenneth L Custer  1 , Lei Shen  1 , Michael Durante  1 , Gerard Oakley  1 , Andrew E Schade  1 , Janelle Sabo  1 , Dipak R Patel  1 , Paul Klekotka  1 , Daniel M Skovronsky  1 ; BLAZE-1 Investigators
Collaborators, Affiliations
Clinical Trial

SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19

Peter Chen et al. N Engl J Med. .

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization.

Methods: In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here.

Results: At the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was -3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was -0.53 (95% confidence interval [CI], -0.98 to -0.08; P = 0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (-0.20; 95% CI, -0.66 to 0.25; P = 0.38) or the 7000-mg dose (0.09; 95% CI, -0.37 to 0.55; P = 0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19-related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group.

Conclusions: In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).

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Figures

Figure 1
Figure 1. Enrollment and Trial Design.
Figure 2
Figure 2. SARS-CoV-2 Viral Load in All Patients and According to Trial Group on Day 7.
Panel A shows the SARS-CoV-2 viral load (as measured by the cycle threshold on reverse-transcriptase–polymerase-chain-reaction assay) for all the patients who received either LY-CoV555 or placebo and for whom viral-load data were available at the time of the interim analysis. The box plots indicate the patients who were not hospitalized, and the red squares indicate those who were hospitalized. Such hospital contact was found to be associated with a high viral load on day 7. The boxes represent interquartile ranges, with the horizontal line in each box representing the median and the whiskers showing the minimum and maximum values (excluding outliers that were more than 1.5 times the values represented at each end of the box). Panel B shows the cumulative probability that patients in each trial group would have the indicated cycle threshold of viral load on day 7.
Figure 3
Figure 3. Symptom Scores from Day 2 to Day 11.
Shown is the difference in the change from baseline (delta value) in symptom scores between the LY-CoV555 group and the placebo group from day 2 to day 11. The symptom scores ranged from 0 to 24 and included eight domains, each of which was graded on a scale of 0 (no symptoms) to 3 (severe symptoms). The 𝙸 bars represent 95% confidence intervals. Details about the symptom-scoring methods are provided in the Supplementary Appendix.
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