170. PROphylaxis for vulnerable paTiEnts at risk of COVID-19 infecTion (PROTECT-V) – a national platform trial
Creators: name: Toby Humphrey1,2,3
name: Stacey2, Hannah
name: Davinder Dosanjh4,5,6
name: Rona Smith1,2,3
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background: </strong>Several patient groups are more vulnerable to COVID-19 infection by virtue of demographics, underlying health conditions or as a consequence of treatments. Such vulnerable patients include individuals with kidney disease requiring dialysis, organ transplant recipients, or autoimmune diseases that require immunosuppression. Despite the introduction of widespread vaccination, there remains a need for antigen independent prophylactic agents against SARS CoV-2. No vaccine is completely effective, new variants of SARS CoV-2 are emerging, and many immunocompromised vulnerable individuals are known to mount a suboptimal response to vaccination. <strong>Methods: </strong>PROTECT-V is a platform trial to test prophylactic interventions against SARS CoV-2 infection in vulnerable patient populations at particularly high risk of COVID-19 and its complications, seeking to either prevent the disease from occurring or reduce the number of serious or life-threatening cases. In PROTECT-V, multiple agents can be evaluated on the same platform across multiple vulnerable populations and sharing placebo groups, with the option of adding additional treatments at later time points as these become available. Furthermore, PROTECT-V is also able to restrict interventions to particular subpopulations or patient groups, as well as adding additional vulnerable patient groups at a later stage such as patients with a sub-optimal vaccine response. The primary endpoint is symptomatic Covid-19 infection, and each agent will be independently evaluated in real time when the required number of events occur. <strong>Results: </strong>The trial commenced with the first intervention, nasal niclosamide and matched placebo in a 1:1 ratio in February 2021. As of 30<sup>th</sup> November, 671 patients from 32 UK sites had been enrolled. The last independent data monitoring committee meeting was in October 2021 and it was recommended to continue the trial as it is. A second inhaled intervention, ciclesonide, will be added in the next few weeks. At that point, patients will be enrolled in a 2:1 ratio, active: placebo. In parallel to the repurposed drug arms, a monoclonal antibody arm, sotrovimab, will enrol vaccine non-responders in a 1:1 ratio, active: placebo. Potential future prophylactic agents such as alternative monoclonal antibody therapies, antivirals or nasal or inhaled agents may be proposed to the UK Prophylaxis Taskforce for endorsement to be included within the platform. <strong>Conclusions: </strong>The PROTECT-V trial platform brings greater efficiency, running multiple sub-trials within one master protocol. It is an exemplar trial demonstrating the success of collaboration in the COVID-19 pandemic. The platform is jointly funded from charitable (LifeArc, Kidney Research UK, Addenbrooke’s Charitable Trust), government funding (NIHR), and industry (Union Therapeutics for the niclosamide arm; GSK for the sotrovimab arm) sources and focuses on patient populations who are often excluded from clinical trials due to complex disease, but remain vulnerable to infection despite the success of vaccination. <strong>Disclosures:</strong> RS receives research funding from Union Therapeutics and GSK, DD receives research funding from GSK. <strong>Figure 1: </strong>PROTECT-V trial schema