Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 Dec;110(6):1467-1477.
doi: 10.1002/cpt.2405. Epub 2021 Oct 16.

First-in-Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID-19

Peter Chen  1 , Gourab Datta  2 , Ying Grace Li  2 , Jenny Chien  2 , Karen Price  2 , Emmanuel Chigutsa  2 , Patricia Brown-Augsburger  2 , Josh Poorbaugh  2 , Jeffrey Fill  2 , Robert J Benschop  2 , Nadine Rouphael  3 , Ariel Kay  3 , Mark J Mulligan  4 , Amit Saxena  4 , William A Fischer  5 , Michael Dougan  6 , Paul Klekotka  2 , Ajay Nirula  2 , Charles Benson  2
Affiliations
Randomized Controlled Trial

First-in-Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID-19

Peter Chen et al. Clin Pharmacol Ther. 2021 Dec.

Abstract

Therapeutics for patients hospitalized with coronavirus disease 2019 (COVID-19) are urgently needed during the pandemic. Bamlanivimab is a potent neutralizing monoclonal antibody that blocks severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) attachment and entry into human cells, which could potentially lead to therapeutic benefit. J2W-MC-PYAA was a randomized, double-blind, sponsor unblinded, placebo-controlled, single ascending dose first-in-human trial (NCT04411628) in hospitalized patients with COVID-19. A total of 24 patients received either placebo or a single dose of bamlanivimab (700 mg, 2,800 mg, or 7,000 mg). The primary objective was assessment of safety and tolerability, including adverse events and serious adverse events, with secondary objectives of pharmacokinetic (PK) and pharmacodynamic analyses. Treatment-emergent adverse event (TEAE) rates were identical in the placebo and pooled bamlanivimab groups (66.7%). There were no apparent dose-related increases in the number or severity of TEAEs. There were no serious adverse events or deaths during the study, and no discontinuations due to adverse events. PKs of bamlanivimab is linear and exposure increased proportionally with dose following single i.v. administration. The half-life was ~ 17 days. These results demonstrate the favorable safety profile of bamlanivimab, and provided the initial critical evaluation of safety, tolerability, and PKs in support of the development of bamlanivimab in several ongoing clinical trials.

PubMed Disclaimer

Conflict of interest statement

P.C. reports grants from Eli Lilly and Company, Gilead, and the National Institutes of Health (NIH), and scientific advisory board member for Eli Lilly and Company, Gilead, Rigel Pharmaceuticals, and Humanigen. N.R. reports grants from Eli Lilly and Company, Merck, Pfizer, Quidel, and Sanofi‐Pasteur. M.J.M. has received research grants from Eli Lilly and Company, Pfizer, and Sanofi, and serves on advisory boards for Pfizer and Meissa Vaccines. W.F. reports research funding provided to UNC from Ridgeback Biopharmaceuticals, Eli Lilly and Company, and Regeneron, consultancy fees from Merck and Roche and served on adjudication committee for Janssen and Syneos. M.D. reports personal fees from Genentech‐Roche, Partner Therapeutics, Tillots Pharma, ORIC Pharmaceuticals, Moderna, AzurRx, SQZ, and WebMD, grants from Novartis and Eli Lilly and Company, and is a scientific advisory board member for Neoleukin Therapeutics. A.S. is an advisory board member for Eli Lilly and Company. G.D., Y.G.L., J.C., K.P., E.C., P.B.A., J.P., J.F., R.J.B., P.K., A.N., and C.B. are employees and shareholders of Eli Lilly and Company. All other authors declared no competing interests for this work.

Figures

Figure 1
Figure 1
Pharmacokinetics (PKs) of bamlanivimab. (a) Mean bamlanivimab serum concentration over time after a single intravenous dose. Error bars represent SD. (b) Detailed analysis of 700 mg bamlanivimab PKs. The PK profiles of all doses remained above the 95% confidence interval (CI) for historical in vitro 90% inhibitory concentration (IC90).
Figure 2
Figure 2
Pharmacodynamics of bamlanivimab. (a) Mean change from baseline (BL) in severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral load over time. (b) Model‐predicted percentage of patients with SARS‐CoV‐2 clearance.
Figure 3
Figure 3
Serum biomarkers. Log10 fold change from baseline in serum concentration of antibodies against severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) (a) spike protein N‐terminal domain (NTD) and (b) nucleocapsid protein (NCP). (c) Coronavirus disease 2019 (COVID‐19) receptor binding domain (RBD) antibody titer by bamlanivimab dose. (d) Correlation of surrogate viral neutralization assay with bamlanivimab serum concentration; table inset shows ratios by bamlanivimab dose. a‐c Data presented are mean ± SE.
Figure 4
Figure 4
Clinical outcomes. (a) Median days to symptom resolution. Symptom resolution is defined as all symptoms on the symptom questionnaire scored as absent. Error bars represent the minimum and maximum values. (b) Change from baseline in coronavirus disease 2019 (COVID‐19) symptom score. (c) Duration of hospitalization (for COVID‐19). Data presented are mean days + SD. (d) Box plot of time to hospital discharge. Error bars represent minimum and maximum vales. Solid bars = first hospital discharge, striped bars = last hospital discharge. Patients with > 1 hospitalization are: 1 placebo, one 700 mg bamlanivimab, zero 2,800 mg bamlanivimab, and one 7,000 mg bamlanivimab. In the 2,800 mg group first discharge = last discharge as no patients had multiple hospitalizations.
See this image and copyright information in PMC

References

    1. Goldman, J.D. et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid‐19. N. Engl. J. Med. 383, 1827–1837 (2020). - PMC - PubMed
    1. Spinner, C.D. et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID‐19: A randomized clinical trial. JAMA 324, 1048–1057 (2020). - PMC - PubMed
    1. Beigel, J.H. et al. Remdesivir for the treatment of covid‐19 ‐ final report. N. Engl. J. Med. 383, 1813–1826 (2020). - PMC - PubMed
    1. Bronte, V. et al. Baricitinib restrains the immune dysregulation in severe COVID‐19 patients. J. Clin. Invest. 130, 6409–6416 (2020). - PMC - PubMed
    1. Stebbing, J. et al. Mechanism of baricitinib supports artificial intelligence‐predicted testing in COVID‐19 patients. EMBO Mol. Med. 12, e12697 (2020). - PMC - PubMed

Publication types

MeSH terms