British Journal of Clinical Pharmacology
Viral clearance, pharmacokinetics and tolerability of ensovibep in patients with mild to moderate COVID‐19: A phase 2a, open‐label, single‐dose escalation study
Manon L M Prins
1
,
Johan L Van Der Plas
1, 2
,
Maurits F.J.M. Vissers
2, 3
,
Cécile L Berends
2, 3
,
Gaby Tresch
4
,
Marianne Soergel
4
,
Elena Fernández
4
,
Nikita Van Den Berge
5
,
Daniël Duijsings
6
,
Christof ZITT
4
,
Vaia Stavropoulou
4
,
Maya Zimmermann
4
,
Roxana F Drake
4
,
Jacobus Burggraaf
2, 3
,
Geert H Groeneveld
1
,
Ingrid M. C. Kamerling
1, 2
2
Centre for Human Drug Research Leiden the Netherlands
|
4
Molecular Partners AG Schlieren Switzerland
|
5
Municipal Health Services (GGD Hollands Midden) Leiden The Netherlands
|
6
Viroclinics Biosciences B.V. Rotterdam The Netherlands
|
Publication type: Journal Article
Publication date: 2022-10-24
scimago Q1
SJR: 1.046
CiteScore: 6.3
Impact factor: 3.1
ISSN: 03065251, 13652125
Pharmacology
Pharmacology (medical)
Abstract
To assess viral clearance, pharmacokinetics, tolerability and symptom evolution following ensovibep administration in symptomatic COVID-19 outpatients.In this open-label, first-in-patient study a single dose of either 225 mg (n = 6) or 600 mg (n = 6) of ensovibep was administered intravenously in outpatients with mild-to-moderate COVID-19 symptoms. Pharmacokinetic profiles were determined (90-day period). Pharmacodynamic assessments consisted of viral load (qPCR and cultures) and symptom questionnaires. Immunogenicity against ensovibep and SARS-CoV-2-neutralizing activity were determined. Safety and tolerability were assessed throughout a 13-week follow-up.Both doses showed similar pharmacokinetics (first-order) with mean half-lives of 14 (SD 5.0) and 13 days (SD 5.7) for the 225- and 600-mg groups, respectively. Pharmacologically relevant serum concentrations were maintained in all subjects for at least 2 weeks postdose, regardless of possible immunogenicity against ensovibep. Viral load changes from baseline at day 15 were 5.1 (SD 0.86) and 5.3 (SD 2.2) log10 copies/mL for the 225- and 600-mg doses, respectively. COVID-19 symptom scores decreased from 10.0 (SD 4.1) and 11.3 (SD 4.0) to 1.6 (SD 3.1) and 3.3 (SD 2.4) in the first week for the 225- and 600-mg groups, respectively. No anti-SARS-CoV-2 neutralizing activity was present predose and all patients had SARS-CoV-2 antibodies at day 91. Adverse events were of mild-to-moderate severity, transient and self-limiting.Single-dose intravenous administration of 225 or 600 mg of ensovibep appeared safe and well tolerated in patients with mild-to-moderate COVID-19. Ensovibep showed favourable pharmacokinetics in patients and the pharmacodynamic results warrant further research in a larger phase 2/3 randomized-controlled trail.
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