Safety, Tolerability and Pharmacokinetics of a High-Dose, Rapid-Infusion Monoclonal Antibody: Phase I Results for Intravenous Sotrovimab 3000 mg
Bibliographic record
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: ) 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".