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. 2025 Nov 24.
doi: 10.1007/s40268-025-00529-2. Online ahead of print.

Safety, Tolerability, Pharmacokinetics, and Viral Pharmacodynamics of the Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection in Participants with Early, Mild-to-Moderate COVID-19: A Randomized Clinical Trial

Anil Gupta  1 , Maria Teresa Perez-Rodríguez  2 , Yaneicy Gonzalez-Rojas  3 , Moti Ramgopal  4 , Almena Free  5 , Jennifer Han  6   7 , Jennifer Moore  8 , Naomi Givens  9 , Phillip J Yates  9 , Jill T Walker  10 , Mary Beth Connolly  11 , Gretja Schnell  12 , Varsha Imber  8 , Rabia Anselm  8 , Lindsay Winograd  13 , Scott Segal  10 , Stephen Harrison  9 , Andrew Skingsley  8 , Melissa Aldinger  12 , Amanda Peppercorn  10 , Jaynier Moya  14
Affiliations

Safety, Tolerability, Pharmacokinetics, and Viral Pharmacodynamics of the Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection in Participants with Early, Mild-to-Moderate COVID-19: A Randomized Clinical Trial

Anil Gupta et al. Drugs R D. .

Abstract

Background and objectives: New coronavirus disease 2019 (COVID-19) therapeutics, including intramuscular (IM) formulations, may increase patient access. In COMET-TAIL, sotrovimab 500 mg IM was non-inferior to 500 mg intravenous (IV) in reducing the risk of COVID-19 progression; however, 250 mg IM was associated with more hospitalizations, despite similar viral load (VL) reductions to 500 mg IM.

Methods: COMET-PEAK was a randomized, three-part study to assess safety, tolerability, and viral pharmacodynamics of sotrovimab in adults with early, mild-to-moderate COVID-19. Parts B/C evaluated sotrovimab 500-mg IV infusion versus 500-mg or 250-mg IM injection. The primary objective was to compare virologic response of sotrovimab IM versus IV (mean area under the curve from day 1 to day 8 [AUCD1-8] of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] VL); 90% confidence interval (CI) limits of 0.5-2.0 indicated equivalence.

Results: Parts B/C included 167 and 157 participants, respectively. Median age range was 42-47 years, and approximately 50% of participants had one or more risk factor for severe disease. The primary objective was met: the ratio of geometric mean VL AUCD1-8 of sotrovimab IM versus IV was 1.04 (90% CI 0.98-1.09; Part B) and 1.02 (90% CI 0.94-1.11; Part C). No new safety signals emerged for sotrovimab; IM administration was well tolerated, with few injection-site reactions.

Conclusions: Both sotrovimab IM doses were equivalent to 500 mg IV with respect to SARS-CoV-2 VL change. IM administration was safe and well tolerated. The validity of VL as a biomarker for COVID-19 progression warrants further study.

Clinical trial registration: NCT04779879 (date of first registration: March 3, 2021), https://classic.

Clinicaltrials: gov/ct2/show/NCT04779879 .

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Conflict of interest statement

Declarations. Conflict of interest: A.G. is a consultant, speaker, and contracted researcher for Vir Biotechnology, Inc. M.T.P.R. is a consultant and speaker for ViiV Healthcare and holds stocks/shares in the company. P.J.Y. and M.B.C., J.H., J.T.W., V.I., R.A., L.W., S.S., S.H., A.S., and A.P. are employed by GSK and hold financial equities in GSK. P.J.Y. and M.B.C. are former employees of GSK. G.S. and M.A. are employees of Vir Biotechnology, Inc. and may hold stocks/shares in the company. Y.G.R., M.R., A.F and J.M. report no conflicts of interest in this work. Availability of data and materials: Anonymized individual participant data and study documents can be requested for further research from https://www.gsk-studyregister.com/en/ . Ethics approval: This study was conducted in accordance with consensus ethical principles derived from international guidelines including the Declaration of Helsinki, Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice Guidelines, and applicable country-specific requirements, including US 21 Code of Federal Regulations 312.3(b) for constitution of independent ethics committees. The full names of the ethics committees and institutional review boards that approved the study are included in the ESM. Consent to participate: Written informed consent was obtained from each participant prior to the performance of any study-specific procedures. Each participant was provided with as much time as necessary to review the informed consent form, to inquire about details of the trial, and to decide whether to participate in the study. Consent for publication: Not applicable. Author contributions: All authors made a significant contribution to the work reported, whether that was in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the manuscript; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. code availability: These will be made available upon reasonable request to the corresponding author, in accordance with GSK and Vir Biotechnology data sharing policies.

References

    1. Graña C, Ghosn L, Evrenoglou T, Jarde A, Minozzi S, Bergman H, et al. Efficacy and safety of COVID-19 vaccines. Cochrane Database Syst Rev. 2022;12:CD015477. - PubMed
    1. Chi WY, Li YD, Huang HC, Chan TEH, Chow SY, Su JH, et al. COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection. J Biomed Sci. 2022;29:82. - DOI - PubMed - PMC
    1. Kumar S, Saikia D, Bankar M, Saurabh MK, Singh H, Varikasuvu SR, et al. Efficacy of COVID-19 vaccines: a systematic review and network meta-analysis of phase 3 randomized controlled trials. Pharmacol Rep. 2022;74:1228–37. - DOI - PubMed - PMC
    1. Shah A, Coiado OC. COVID-19 vaccine and booster hesitation around the world: a literature review. Front Med (Lausanne). 2023;9:1054557. https://doi.org/10.3389/fmed.2022.1054557 . - DOI - PubMed
    1. Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: a phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018;15(1):e1002493. https://doi.org/10.1371/journal.pmed.1002493 . - DOI - PubMed - PMC

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