Safety and Tolerability Study of Sotrovimab (VIR-7831) Prophylaxis Against COVID-19 Infection in Immunocompromised Individuals with Impaired SARS-CoV-2 Humoral Immunity

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Abstract Background: Since August 2021, multiple vaccines have been approved 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 an exceptionally high risk of infection and more severe illness than non-immunocompromised hosts. Sotrovimab (VIR-7831) is an engineered monoclonal antibody that targets a highly conserved epitope on the SARS-CoV-2 spike glycoprotein. It is neither renally excreted nor metabolized by P450 (CYP) enzymes; therefore, interactions with concomitant medications are unlikely, which is an important consideration for patients receiving multiple immunosuppressive medications. In this Phase II open-label safety and tolerability study protocol, we propose to evaluate the safety and tolerability of sotrovimab as pre-exposure prophylaxis for immunocompromised individuals.Methods: We will enroll a total of 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 between two sequential doses of sotrovimab. Phase 2 will expand this population to 50 participants to examine rates of infusion-related reactions (IRR) with a 30-minute 500mg sotrovimab IV infusion. Phase 3 will be an expansion cohort for further assessment of the safety and tolerability of sotrovimab in this patient population. In Phase 4, the first 10 patients receiving 2000mg IV of sotrovimab on the second sotrovimab infusion day (Treatment Day 2) will comprise a lead-in safety cohort that will inform the duration of observation following administration of the drug, with the observation period being reduced from two hours to one hour for the remaining study population if none of these patients have a grade 3-4 infusion-related reaction. The patients will be followed for safety and COVID-19 events for an additional 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 to study the safety and tolerability of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection and evaluate its PK in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity. We also aim to determine COVID-19 infections over the study period and self-reported quality of life measures over the course of the study.Trial registration: ClinicalTrials.gov Identifier: NCT05210101

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