Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection

This is a multi-centre, double blind, randomized, placebo-controlled study of multiple applications of a single concentration of XF-73 nasal gel to assess the microbiological effect of XF-73 on commensal S. aureus nasal carriage in patients scheduled for surgical procedures deemed to be at high risk of post-operative S. aureus infection. The study is divided in 4 periods: screening (days -14 to -1) randomization (days -10 to -1), treatment (days -1 and 0) and follow-up (post-last study dose to day 30 or day 90 if an implant is inserted during surgery). Day 0 is the calendar day in which surgery takes place. Only patients who test positive to S. aureus by a centrally-performed rapid diagnostic test will be enrolled in the study. Approximately 125 patients will be randomly allocated in a 1:1 ratio to 0.2% w/w XF-73 nasal gel treatment OR placebo to match XF-73 nasal gel. The study drug, 0.2% w/w XF-73, or matched placebo will be administered 4 times into each nostril over 24 hours prior to surgery and then a single application immediately upon closure of surgical wound. Additionally, patients may undergo chlorhexidine skin decolonisation ahead of surgery and receive perioperative prophylactic systemic antibiotics in accordance with local practice. Efficacy will be assessed by S. aureus colonisation from screening to 7 days after surgery as well as by incidence of post-operative staphylococcal infections and use of anti-staphylococcal antibiotics post-surgery. Safety will be assessed by reported adverse events (AEs) from screening up to Day 7 as well as vital signs, physical examination (ENT), clinical laboratory assessments (haematology, clinical chemistry, and urinalysis) and Smell Identification Tests at different time points throughout the study. The maximum study duration will be 45 or 105 days for each individual (from screening to post-study follow-up visit) depending on whether a foreign implant was inserted during surgery. An independent data monitoring committee (IDMC) will be set up which will review the safety information from the study, the incidence of post-operative staphylococcal infections and to ensure that the balance of benefits and risks of participating in the study does not change.