Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection
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|ClinicalTrials.gov Identifier: NCT03915470|
Recruitment Status : Completed
First Posted : April 16, 2019
Results First Posted : June 1, 2022
Last Update Posted : June 1, 2022
|Condition or disease||Intervention/treatment||Phase|
|Staphylococcal Infections Surgical Site Infection||Drug: XF-73 Drug: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||124 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||Double blind.|
|Official Title:||A Phase 2 Study to Assess the Effect of a Repeated Dose of XF-73 Nasal Gel on the Microbiological Burden of Commensal Staphylococcus Aureus Nasal Carriage in Surgical Patients at Risk of Post-operative Staphylococcal Infections|
|Actual Study Start Date :||August 29, 2019|
|Actual Primary Completion Date :||January 4, 2021|
|Actual Study Completion Date :||March 29, 2021|
0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel for a cumulative dose of 6.0 mg of XF-73.
XF-73 is a dicationic porphyrin derivative having potent bactericidal properties with a novel mode of action.
Other Name: Exeporfinium chloride
Placebo Comparator: Placebo
0.3 mL applications in each naris of placebo to match XF-73 nasal gel.
Placebo to match XF-73 nasal gel for colour and viscosity.
Other Name: Matched Placebo
- Change in S. Aureus Log CFU/mL From Baseline to Pre-surgery [ Time Frame: Baseline (Day-10 to Day-1) to immediately prior to surgery (Day 0) ]To demonstrate the efficacy of a 0.2% XF-73 nasal gel in reducing the microbiological burden of nasal S. aureus measured as change in colony forming units (CFU) per millilitre (mL) from baseline to immediately prior to surgery in a patient population at risk of post-operative staphylococcal infection
- Change in S. Aureus Log CFU/mL From Baseline to Immediately Post-surgery [ Time Frame: From baseline (day -10 to Day -1) to immediately post surgery (Day 0) ]To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden measured as CFUs/mL in follow-up after last administration.
- Change in S. Aureus Log CFU/mL From Baseline to 48 Hours After Surgery [ Time Frame: From baseline to follow-up at 48 hours after surgery ]To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden measured as CFUs/mL in follow-up 48 hours after last administration.
- Change in S. Aureus Log CFU/mL From Baseline to Immediately After Surgery to 6 Days (± 24hours) After Surgery [ Time Frame: From baseline to follow-up Day 6 ± 24hours after surgery ]To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden measured as CFUs/mL in follow-up 7 days after last administration.
- Number of Participants With Staphylococcal Post-operative Infections During the 30-day Period After Surgery (90 Days in the Case of Foreign Implant) [ Time Frame: From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant) ]To assess the effect of XF-73 on S. aureus nasal carriage in the prevention of post-operative staphylococcal infections (surgical site infection, blood stream infections, and others) during the 30 days post-surgery (90 days in the case of a foreign implant).
- Incidence of Treatment-emergent Adverse Events From the First Dose of Study Medication to 6 Days (± 24hours) After Last Dose of Study Medication. [ Time Frame: Immediately prior to surgery until Day 6 ± 24hours. ]To describe the safety and tolerability of multiple administrations of a 0.2% XF-73 nasal gel in a population of surgical patients at risk of post-operative staphylococcal infections.
- Changes in Nasal Examination. [ Time Frame: From Randomisation (Day -10 to Day -1) until 48hours ± 24hours post surgery. ]To describe the safety and tolerability of multiple administrations of a 0.2% XF-73 nasal gel in a population of surgical patients at risk of post-operative staphylococcal infections by comparison of changes in ENT specialist nasal examination findings from randomisation to 48hours ± 24hours post surgery.
- Changes in Brief Smell Identification Test (B-SIT). [ Time Frame: From Randomisation (Day -10 to Day -1) until Day 6 ± 24hours post surgery ]
To describe the safety and tolerability of multiple administrations of a 0.2% XF-73 nasal gel in a population of surgical patients at risk of post-operative staphylococcal infections by comparison of Brief Smell Identification Test (B-SIT) score, assessment and percentile ranking changes from prior to first dose until Day 6 ±24h post surgery.
Patients are asked to identify 12 unique smells; the more smells they identify correctly the higher the score (0-12). Comparison of the individual patient score is then made against their expected percentile ranking dependent on age and sex of the general population to determine if their percentile ranking is normal, abnormal relative to age or deficit relative to younger persons.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03915470
|Study Chair:||Jesus M Gonzalez Moreno, MD||Destiny Pharma Plc|
|Study Director:||Jim P Lees, BSc||Destiny Pharma Plc|