Ensovibep, a SARS‐CoV‐2 antiviral designed ankyrin repeat protein, is safe and well tolerated in healthy volunteers: Results of a first‐in‐human, ascending single‐dose Phase 1 study

Aims This study aimed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ensovibep, a designed ankyrin repeat protein antiviral being evaluated as a COVID‐19 treatment, in healthy volunteers in a first‐in‐human ascending single‐dose study. Methods Subjects were...

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Bibliographic Details
Published in:	British journal of clinical pharmacology Vol. 89; no. 7; pp. 2295 - 2303
Main Authors:	Stojcheva, Nina, Gladman, Stacy, Soergel, Marianne, Zitt, Christof, Drake, Roxana, Lockett, Tony, Marchand, Carine, Fustier, Pierre, Stavropoulou, Vaia, Fernandez, Elena, Pettigiani, Nathana Lopes, Watkins, Kate, Puri, Adeep, Watson, Randall, Legenne, Philippe, Stumpp, Michael T., Boyce, Malcolm
Format:	Journal Article
Language:	English
Published:	England 01-07-2023
Subjects:	antiviral COVID‐19 DARPin ensovibep omicron variants of concern COVID-19 ensovibep omicron DARPin variants of concern antiviral
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Summary:	Aims This study aimed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ensovibep, a designed ankyrin repeat protein antiviral being evaluated as a COVID‐19 treatment, in healthy volunteers in a first‐in‐human ascending single‐dose study. Methods Subjects were dosed intravenously, in a randomized double‐blinded manner, with either ensovibep at 3, 9 or 20 mg/kg or with placebo, and followed until Day 100. PK and safety were assessed throughout the study duration. Immunogenicity and PD via viral neutralization in serum were also assessed. Results All adverse events were of mild to moderate severity, and no serious adverse events were observed. One subject who received the 20‐mg/kg dose presented with moderate hypersensitivity vasculitis 3 weeks after infusion, which fully resolved using standard procedures. In most subjects ensovibep showed expected mono‐exponential decline with a half‐life of around 2 weeks. Anti‐drug antibodies were detected in 15 of 17 subjects, with the earliest onset detected on Day 29. Viral neutralization assays on subject serum showed effective viral neutralization over the first 3 weeks following dosing with titre values in a dose dependent manner. Conclusion Ensovibep proved safe in this first‐in‐human safety study and exhibited PK and PD parameters consistent with the expected treatment period required for acute COVID‐19 infection.
Bibliography:	Funding information The authors confirm that the Principal Investigator for this paper is Malcolm Boyce BSc MB ChB FRCP FFPM HonFBPhS FRQA FCMI QP MD, and that he had direct clinical responsibility for the patients. Molecular Partners AG. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0306-5251 1365-2125
DOI:	10.1111/bcp.15747