Safety and tolerability study of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity.

Autor: Gonzalez-Bocco IH; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA. Isabel_gonzalez-bocco@dfci.harvard.edu.; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA. Isabel_gonzalez-bocco@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. Isabel_gonzalez-bocco@dfci.harvard.edu., Beluch K; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA., Cho A; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA., Lahoud C; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Reyes FA; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Moshovitis DG; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA.; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA., Unger-Mochrie GM; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA., Wang W; Harvard Medical School, Boston, MA, USA.; Medicine Department, Brigham and Women's Hospital, Boston, MA, USA., Hammond SP; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Division of Infectious Disease, Massachusetts General Hospital, Boston, MA, USA., Manne-Goehler J; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Division of Infectious Disease, Massachusetts General Hospital, Boston, MA, USA., Koo S; Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA. skoo@bwh.harvard.edu.; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA. skoo@bwh.harvard.edu.; Harvard Medical School, Boston, MA, USA. skoo@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Pilot and feasibility studies [Pilot Feasibility Stud] 2023 Jun 16; Vol. 9 (1), pp. 100. Date of Electronic Publication: 2023 Jun 16.
DOI: 10.1186/s40814-023-01325-y
Abstrakt: Background: Multiple vaccines have been approved since August 2021 to prevent infection with SARS-CoV-2; however, 20-40% of immunocompromised people fail to develop SARS-CoV-2 spike antibodies after COVID-19 vaccination and remain at high risk of infection and more severe illness than non-immunocompromised hosts. Sotrovimab (VIR-7831) is a monoclonal neutralizing antibody that binds a conserved epitope on the SARS-CoV-2 spike protein. It is neither renally excreted nor metabolized by P450 enzymes and therefore unlikely to interact with concomitant medications (e.g., immunosuppressive medications). In this open-label feasibility study protocol, we will define the optimal dose and dosing interval of sotrovimab as pre-exposure prophylaxis for immunocompromised individuals as well as its safety and tolerability in this population specifically.
Methods: We will enroll 93 eligible immunocompromised adults with a negative or low-positive (< 50 U/mL) SARS-CoV-2 spike antibody. In phase 1, the first 10 patients will participate in a lead-in pharmacokinetics (PK) cohort study to determine the optimal dosing interval. Phase 2 will expand this population to 50 participants to examine rates of infusion-related reactions (IRR) with a 30-min 500 mg sotrovimab IV infusion. Phase 3 will be an expansion cohort for further assessment of the safety and tolerability of sotrovimab. In phase 4, the first 10 patients receiving 2000 mg IV of sotrovimab on the second sotrovimab infusion day will comprise a lead-in safety cohort that will inform the duration of observation following administration of the drug. The patients will be followed for safety and COVID-19 events for 36 weeks after the second dose.
Discussion: In a previous phase III randomized, placebo-controlled pivotal trial, there were no significant differences in the prevalence of adverse events in patients receiving sotrovimab vs. placebo. Thus, we propose an open-label feasibility study protocol of sotrovimab as pre-exposure prophylaxis for immunocompromised individuals to evaluate its PK in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity and define optimal dosing intervals. We also aim to determine COVID-19 infections over the study period and self-reported quality of life measures throughout the study.
Trial Registration: ClinicalTrials.gov Identifier: NCT05210101.
(© 2023. The Author(s).)
Databáze: MEDLINE
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