Safety, Tolerability and Pharmacokinetics of a High-Dose, Rapid-Infusion Monoclonal Antibody - Phase I Results for Intravenous Sotrovimab 3000 mg

Q: Why were higher intravenous doses of sotrovimab studied?

SARS-CoV-2 variants reduced sotrovimab neutralisation activity in vitro, prompting evaluation of higher (>500 mg) intravenous doses.

Sep 28, 2026

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Background and objectives: Due to SARS-CoV-2 variants with lower sotrovimab neutralisation activity in vitro, higher (>500 mg) intravenous doses were explored. This phase I study assessed safety, tolerability, and pharmacokinetics of a single 3000 mg intravenous sotrovimab dose. Methods: A phase I, open-label, single-arm trial in healthy adults administered sotrovimab 3000 mg over 60 minutes and monitored adverse events through week 35 and pharmacokinetics through week 24.

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Clinical Trial Registration

Introduction

Drugs in R&D (2025) 25:367–376 [https://doi.org/10.1007/s40268-025-00530-9](https://doi.org/10.1007/s40268-025-00530-9) Safety, Tolerability and Pharmacokinetics of a High‑Dose, Rapid‑Infusion Monoclonal Antibody: Phase I Results for Intravenous Sotrovimab 3000 mg Yasmin Sánchez‑Pearson1 · Jennifer Moore1 · Jerzy Daniluk2 · Sookti Bhangu3 · Sergio Parra4 · Asma El Zailik4 · Prosenjit Sarkar5 · Alicia Aylott6 · Farai Moyo1 · Amanda Peppercorn7 · Andrew Skingsley1 Received: 4 April 2025 / Accepted: 10 November 2025 / Published online: 1 December 2025 © The Author(s) 2025 Abstract Background and Objectives The emergence of severe acute respiratory syndrome coronavirus 2 variants against which sotrovimab has lower in vitro neutralisation activity has led to the exploration of higher (> 500-mg intravenous) doses. This study evaluated the safety, tolerability and pharmacokinetics of intravenous sotrovimab 3000 mg. Methods We conducted a phase I, open-label, single-arm study in healthy adults. Participants were administered a single 3000-mg dose of intravenous sotrovimab (100 mg/mL) over 60 min (50 mg/min) . Adverse events, serious adverse events and adverse events of special interest were assessed through week 35. Sotrovimab pharmacokinetics were evaluated through week 24. Results Of 100 participants enrolled, 98 received sotrovimab (median age 42.5 [range 18–64] years; 52% male; mean body mass index 25.25 kg/m2) and 96 completed the study. Overall, 37%(n = 36/98) of the participants reported adverse events, five of which were considered to be treatment related. The most common type of event was infection (13%; n = 13/98) with upper respiratory tract infection (9%; n = 9/98) being frequent. Two Grade 1 adverse events of special interest were reported. There were no serious adverse events, deaths or adverse events leading to discontinuation. Pharmacokinetic results were in line with expectations for this dose of sotrovimab, assuming linear dose-proportional pharmacokinetics, based on the population pharmacokinetic model of sotrovimab. Conclusions Intravenous sotrovimab 3000 mg, administered over 60 min, was generally well tolerated by healthy volunteers, with a low incidence of adverse events and adverse events of special interest, no documented serious adverse events and no adverse events leading to discontinuation. Pharmacokinetic results were in line with expectations for a 3000-mg dose, assuming linear dose-proportional pharmacokinetics. Clinical Trial Registration ClinicalTrials.gov NCT05280717; date of registration 4 March, 2022. 1 Introduction Although coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is no longer classified as a global health emergency, it continues to present a substantial public health burden [1–3] . Vaccines developed against SARS-CoV-2 significantly reduced mortality worldwide; however, the emergence of new variants has diminished their effectiveness in reducing morbidity [4] . As a result, despite vaccination and population immunity, breakthrough infections continue to result in hospitalisations, and there is a continued need for therapeutics, particularly among groups unable to receive oral direct-acting antivirals. Sotrovimab is a dual-action, Fc-engineered, human immunoglobulin G monoclonal antibody (mAb) with potent neutralising activity against the spike protein of the wild-type SARS-CoV-2, all pre-Omicron variants anda number of Omicron variants (e.g. Omicron XBB.1.5.10, EG.5. 1 and XBB.2. 3, viral variants that showed a relatively low [< 10-fold] change in activity relative to wild type in in vitro assays) [5–7] . The Fc domain of sotrovimab includes the two-amino-acid ‘LS’ modification that extends the antibody’s half-life and improves its bioavailability [5 , 8–10] . Based on population pharmacokinetic analyses from the sotrovimab development programme, following a 15-min to 1-h 500-mg intra

FAQs

Why were higher intravenous doses of sotrovimab studied?

SARS-CoV-2 variants reduced sotrovimab neutralisation activity in vitro, prompting evaluation of higher (>500 mg) intravenous doses.

How was the phase I study conducted and what was the dosing schedule?

The study was a phase I, open-label, single-arm trial in healthy adults. Participants received a single 3000 mg intravenous sotrovimab dose over 60 minutes.

What were the key safety outcomes for the 3000 mg dose?

Adverse events were reported by 37% of participants, and only five events were considered treatment related. There were no serious adverse events, deaths, or discontinuations due to adverse events.

What did pharmacokinetic results show for this dose?

Pharmacokinetic results aligned with expectations for a 3000 mg dose under linear, dose-proportional pharmacokinetics based on the population pharmacokinetic model.

Sep 28, 2026

Uploaded by Callum