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Trial record 16 of 24 for:    Porphyrins

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 : Recruiting
First Posted : April 16, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Destiny Pharma Plc

Tracking Information
First Submitted Date  ICMJE April 1, 2019
First Posted Date  ICMJE April 16, 2019
Last Update Posted Date August 22, 2019
Actual Study Start Date  ICMJE June 11, 2019
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
Change in S. aureus log CFU/mL from baseline to pre-surgery [ Time Frame: Baseline to immediately prior to 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03915470 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
  • Difference in AUC of S. aureus log CFU/mL from baseline to pre-surgery [ Time Frame: Baseline to immediately prior to surgery ]
    To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden from baseline to pre-surgery and from baseline to immediately post-surgery measured as area under the curve (AUC) of S. aureus log CFUs/mL over time.
  • Difference in AUC of S. aureus log CFU/mL from baseline to immediately post-surgery [ Time Frame: Baseline to immediately post surgery ]
    To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden from baseline to pre-surgery and from baseline to immediately post-surgery measured as area under the curve (AUC) of S. aureus log CFUs/mL over time.
  • Change in S. aureus log CFU/mL from immediately after surgery to 48 hours after surgery [ Time Frame: From immediately after surgery 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 after last administration.
  • Change in S. aureus log CFU/mL from immediately after surgery to 6 days (± 24hrs) after surgery [ Time Frame: From immediately after surgery to follow-up Day 6 ± 24hrs 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 after last administration.
  • Percentage of patients reaching a specific reduction in S. aureus carriage prior to surgery, immediately post-surgery and on Day 6 ± 24hrs. [ Time Frame: Immediately prior to surgery, immediately post-surgery and on Day 6 ± 24hrs. ]
    To explore the efficacy of XF-73 in reducing the burden of S. aureus carriage at the patient level.
  • Difference in the incidence of 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 (± 24hrs) after last dose of study medication. [ Time Frame: Immediately prior to surgery until Day 6 ± 24hrs. ]
    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.
  • Change in mean blood pressure (mmHg) [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    Mean systolic and diastolic blood pressure (mmHg) changes from baseline, at post study treatment 48h ± 24h and Day 6± 24h.
  • Change in mean heart rate (bpm) [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    Mean heart rate (bpm) changes from baseline, at post study treatment 48h ± 24h and Day 6± 24h.
  • Changes in nasal examination. [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    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 prior to first dose at 48h ± 24h and Day 6± 24h.
  • Changes in brief smell identification test (B-SIT). [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    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 B-SIT score, assessment and percentile ranking changes from prior to first dose at Day 6± 24h.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Difference in AUC of S. aureus log CFU/mL from baseline to pre-surgery [ Time Frame: Baseline to immediately prior to surgery ]
    To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden from baseline to pre-surgery and from baseline to immediately post-surgery measured as area under the curve (AUC) of S. aureus log CFUs/mL over time.
  • Difference in AUC of S. aureus log CFU/mL from baseline to immediately post-surgery [ Time Frame: Baseline to immediately post surgery ]
    To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden from baseline to pre-surgery and from baseline to immediately post-surgery measured as area under the curve (AUC) of S. aureus log CFUs/mL over time.
  • Change in S. aureus log CFU/mL from immediately after surgery to 48 hours after surgery [ Time Frame: From immediately after surgery 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 after last administration.
  • Change in S. aureus log CFU/mL from immediately after surgery to 6 days (± 24hrs) after surgery [ Time Frame: From immediately after surgery to follow-up Day 6 ± 24hrs 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 after last administration.
  • Percentage of patients reaching a specific reduction in S. aureus carriage prior to surgery, immediately post-surgery and on Day 6 ± 24hrs. [ Time Frame: Immediately prior to surgery, immediately post-surgery and on Day 6 ± 24hrs. ]
    To explore the efficacy of XF-73 in reducing the burden of S. aureus carriage at the patient level.
  • Difference in the incidence of 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 (± 24hrs) after last dose of study medication. [ Time Frame: Immediately prior to surgery until Day 6 ± 24hrs. ]
    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.
  • Change in mean blood pressure (mmHg) [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    Mean blood pressure (mmHg) changes from baseline, at post study treatment 48h ± 24h and Day 6± 24h.
  • Change in mean heart rate (bpm) [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    Mean heart rate (bpm) changes from baseline, at post study treatment 48h ± 24h and Day 6± 24h.
  • Changes in nasal examination. [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    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 prior to first dose at 48h ± 24h and Day 6± 24h.
  • Changes in brief smell identification test (B-SIT). [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    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 B-SIT score, assessment and percentile ranking changes from prior to first dose at Day 6± 24h.
Current Other Pre-specified Outcome Measures
 (submitted: April 15, 2019)
  • Number prescriptions of anti-staphylococcal antibiotics. [ Time Frame: From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant) ]
    To describe the frequency in prescription of post-operative anti-staphylococcal antibiotics in terms of number prescriptions, except those provided for prophylaxis as local standard of care (SOC), during the 30 day post-surgery period (90 days in the case of an object implant) reported separately.
  • Number of patients requiring anti-staphylococcal antibiotics. [ Time Frame: From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant) ]
    To describe the frequency in terms of the number of patients requiring anti-staphylococcal antibiotics, except those provided for prophylaxis as local standard of care (SOC), during the 30 day post-surgery period (90 days in the case of an object implant) reported separately.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S. Aureus in Patients at Risk of Post-op Staphylococcal Infection
Official Title  ICMJE 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
Brief 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 200 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 9 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.
Detailed 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 -3) randomization (days -10 to -2), 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 200 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:
Double blind.
Primary Purpose: Prevention
Condition  ICMJE
  • Staphylococcal Infections
  • Surgical Site Infection
Intervention  ICMJE
  • Drug: XF-73
    XF-73 is a dicationic porphyrin derivative having potent bactericidal properties with a novel mode of action.
    Other Name: Exeporfinium chloride
  • Drug: Placebo
    Placebo to match XF-73 nasal gel for colour and viscosity.
    Other Name: Matched Placebo
Study Arms  ICMJE
  • Experimental: XF-73
    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.
    Intervention: Drug: XF-73
  • Placebo Comparator: Placebo
    0.3 mL applications in each naris of placebo to match XF-73 nasal gel.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 15, 2019)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Clinically significant abnormalities in vital signs or laboratory analyses at 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Director of Clinical Projects +44 (0)1273 704440 participation@destinypharma.com
Listed Location Countries  ICMJE Georgia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03915470
Other Study ID Numbers  ICMJE XF-73B07
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Destiny Pharma Plc
Study Sponsor  ICMJE Destiny Pharma Plc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Jesus M Gonzalez Moreno, MD Destiny Pharma Plc
Study Director: Jim P Lees, BSc Destiny Pharma Plc
PRS Account Destiny Pharma Plc
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP