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

Surgical Site Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03915470
• Other study ID #: XF-73B07
• Status: Completed
• Phase: Phase 2
• Start date: August 29, 2019
• Est. completion date: March 29, 2021

Study information

• Verified date: May 2022
• Source: Destiny Pharma Plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study looks at the difference between XF-73 and placebo in reducing the carriage of a bacteria S. aureus in the nose before, during and after heart surgery. Only people who normally have S.aureus in their nose will be enrolled onto the study. This will be confirmed by analysis of a nasal swab (a cotton bud placed in the nose) before entering the study. It is expected 125 people will participate in this study. Participation will be confirmed by analysis of a nasal swab (a cotton bud placed in the nose) before entering the study. XF-73 or placebo will be given 5 times, with an equal chance of participants receiving either XF-73 or placebo. During the hospital stay more nasal swabs will be taken to determine the amount of S.aureus present in the participant's nose. Other tests such as blood samples, blood pressure and an examination of the nose and sense of smell will be performed as part of the safety assessment. After the hospital stay participants will be followed up for 30 days or if a device has been inserted into the body as part of the surgery for 90 days to look at the rates of post-operative infection between the placebo and XF-73 groups. The study will run for about 18 months. During this period, an independent data monitoring committee will review the study to make sure that the balance of benefits and risks of participating in the study does not change.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: March 29, 2021
• Est. primary completion date: January 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Individuals who meet all of the following criteria are eligible to participate in the study.

1. Male or female patients between 18 and 75 years of age.

2. Patients who are confirmed nasal S. aureus carriers by polymerase chain reaction (PCR) screen assay, and due to undergo surgical procedure.

3. Patients who are willing to provide written informed consent.

4. Patients who are willing and able (as per Investigator judgment) to complete all protocol specified visits and assessments.

5. Woman of childbearing potential* with a negative urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin (hCG)).

• Women of childbearing potential are defined as those women between menarche and menopause who have not undergone permanent sterilisation. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

Individuals who meet any of the following criteria are not eligible to participate in the study.

1. Pregnancy (current) or currently lactating.

2. Uncontrolled acute or chronic illness (as determined by the investigator) in addition to those requiring the planned surgical intervention.

3. History of atopy, allergic reactions or hypersensitivity to the study medication or its components.

4. Current upper respiratory tract infection, cold or influenza with significant nasal symptoms that might impact on the patient's ability to comply with the gel application procedure.

5. History of photosensitivity.

6. Family history of porphyria.

7. Use of intra-nasal topical or systemic antibiotics or anti-infectives within the last 4 weeks before screening. (Patients who screen positive for nasal carriage of S. aureus and receive topical or systemic antibiotics or anti-infectives which are not part of their prophylactic peri-operative SOC between screening and first dose of investigational medicinal product (IMP) will be excluded from the study.) The use of intra-nasal antibiotics or anti-infectives other than the study medication prior to surgery is not allowed.

8. Use of other prescribed or over the counter nasal medication in the last 14 days, or oral decongestants in the last 7 days before first administration of study drug.

9. Participation in a clinical trial within the last 12 weeks before first administration of study drug.

10. Contemporaneous clinically significant abnormalities in vital signs or laboratory analyses reported within 14 days prior to randomization which in the opinion of the Investigator would preclude from the safety assessment of the medication under study.

11. Nasal polyps or significant anatomical or other nasal abnormality that would prevent from appropriate administration of the study treatment or represent an excessive risk for the patient's participation.

12. History of nasal surgery including cauterization.

13. A recent history of frequent epistaxis and/or an episode of epistaxis within 3 months of the planned surgery.

14. Use of in situ nasal jewellery or existence of open nasal piercings.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Staphylococcal Infections
• Surgical Site Infection
• Surgical Wound Infection

Intervention

Drug:
• XF-73
XF-73 is a dicationic porphyrin derivative having potent bactericidal properties with a novel mode of action.
• Placebo
Placebo to match XF-73 nasal gel for colour and viscosity.

Locations

Country	Name	City	State
Georgia	Ltd Clinic LJ	Kutaisi
Georgia	JSC Evex Hospitals	Tbilisi
Georgia	Ltd "Open Heart"	Tbilisi
Georgia	Ltd Acad. G.Chapidze Emergency Cardiology Center	Tbilisi
Georgia	Ltd Bokhua Memorial Cardiovascular Center	Tbilisi
Georgia	Ltd Cardiology Clinic Guli	Tbilisi
Georgia	Ltd Clinic Jerarsi	Tbilisi
Georgia	Ltd Israel-Georgia Medical Research Clinic Helsicore	Tbilisi
Georgia	Ltd Tbilisi Heart and Vascular Clinic	Tbilisi
Georgia	Ltd Tbilisi Heart Center	Tbilisi
Serbia	Clinic for Cardiac Surgery, Institute for Cardiovascular Disease-Deinje	Belgrade
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Center Nis	Niš
Serbia	Institute for Cardiovascular Disease of Vojvodina	Sremska Kamenica
United States	University of Missouri Health Care	Columbia	Missouri
United States	MercyOne Iowa Heart Center	Des Moines	Iowa
United States	University of Florida	Gainesville	Florida
United States	Memorial Hermann - Memorial City Medical Center	Houston	Texas
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Snake River Research, PLLC	Pocatello	Idaho
United States	CHI Franciscan Research Center	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Destiny Pharma Plc

Countries where clinical trial is conducted

United States,  Georgia,  Serbia, 

References & Publications (1)

Mangino JE, Firstenberg MS, Milewski RKC, Rhys-Williams W, Lees JP, Dane A, Love WG, Gonzalez Moreno J. Exeporfinium chloride (XF-73) nasal gel dosed over 24 hours prior to surgery significantly reduced Staphylococcus aureus nasal carriage in cardiac surg — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in S. Aureus Log CFU/mL From Baseline to Pre-surgery	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	Baseline (Day-10 to Day-1) to immediately prior to surgery (Day 0)
Secondary	Change in S. Aureus Log CFU/mL From Baseline to Immediately Post-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 after last administration.	From baseline (day -10 to Day -1) to immediately post surgery (Day 0)
Secondary	Change in S. Aureus Log CFU/mL From Baseline to 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.	From baseline to follow-up at 48 hours after surgery
Secondary	Change in S. Aureus Log CFU/mL From Baseline to Immediately After Surgery to 6 Days (± 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.	From baseline to follow-up Day 6 ± 24hours after surgery
Secondary	Number of Participants With Staphylococcal Post-operative Infections During the 30-day Period After 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).	From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant)
Secondary	Incidence of Treatment-emergent Adverse Events From the First Dose of Study Medication to 6 Days (± 24hours) After Last Dose of Study Medication.	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.	Immediately prior to surgery until Day 6 ± 24hours.
Secondary	Changes in Nasal Examination.	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.	From Randomisation (Day -10 to Day -1) until 48hours ± 24hours post surgery.
Secondary	Changes in Brief Smell Identification Test (B-SIT).	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.	From Randomisation (Day -10 to Day -1) until Day 6 ± 24hours post surgery