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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03915470
Recruitment Status : Completed
First Posted : April 16, 2019
Results First Posted : June 1, 2022
Last Update Posted : June 1, 2022
Sponsor:
Information provided by (Responsible Party):
Destiny Pharma Plc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Staphylococcal Infections
Surgical Site Infection
Interventions Drug: XF-73
Drug: Placebo
Enrollment 124
Recruitment Details Participants at risk of post surgery staphylococcal infections were recruited based on physician assessment across 20 sites (14 enrolling) between June 2019 and March 2021. The first participant was enrolled on 29 August 2019 and the last participant was enrolled on 29 December 2020.
Pre-assignment Details 124 enrolled participants
Arm/Group Title XF-73 Placebo
Hide Arm/Group Description Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Period Title: Overall Study
Started 63 61
Completed 57 [1] 59 [2]
Not Completed 6 2
Reason Not Completed
Death             3             1
Adverse Event             1             0
Physician Decision             1             0
XF-73: Failure to meet RND criteria, Placebo: Surgery was cancelled             1             1
[1]
63 - 6 (discontinued intervention)
[2]
61-2 (discontinued intervention)
Arm/Group Title XF-73 Placebo Total
Hide Arm/Group Description

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: XF-73 is a dicationic porphyrin derivative having potent bactericidal properties with a novel mode of action.

0.3 mL applications in each naris of placebo to match XF-73 nasal gel.

Placebo: Placebo to match XF-73 nasal gel for colour and viscosity.

Total of all reporting groups
Overall Number of Baseline Participants 63 61 124
Hide Baseline Analysis Population Description
Safety Population: all patients who received at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants 61 participants 124 participants
60.5  (9.93) 61.2  (8.79) 60.9  (9.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 61 participants 124 participants
Female
17
  27.0%
13
  21.3%
30
  24.2%
Male
46
  73.0%
48
  78.7%
94
  75.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 61 participants 124 participants
Hispanic or Latino
1
   1.6%
3
   4.9%
4
   3.2%
Not Hispanic or Latino
59
  93.7%
56
  91.8%
115
  92.7%
Unknown or Not Reported
3
   4.8%
2
   3.3%
5
   4.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 61 participants 124 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
63
 100.0%
61
 100.0%
124
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 63 participants 61 participants 124 participants
4 2 6
Georgia Number Analyzed 63 participants 61 participants 124 participants
55 56 111
Serbia Number Analyzed 63 participants 61 participants 124 participants
4 3 7
Body Mass Index (BMI)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 62 participants 59 participants 121 participants
30.410  (4.4140) 30.055  (4.7368) 30.237  (4.5586)
[1]
Measure Description: units: kg/m2 Mean (Standard Deviation)
[2]
Measure Analysis Population Description: Intent-To-Treat Population Set
1.Primary Outcome
Title Change in S. Aureus Log CFU/mL From Baseline to Pre-surgery
Hide Description 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
Time Frame Baseline (Day-10 to Day-1) to immediately prior to surgery (Day 0)
Hide Outcome Measure Data
Hide Analysis Population Description
microbiological Intent-To-Treat (micro ITT) set: all patients who were randomized, received at least 1 dose of study drug, have at least 1 post-baseline assessment of S. aureus log10 CFU/mL and who have a log10 CFU/mL result at baseline greater than 0, i.e. all patients in the mITT set with a quantifiable baseline microbiological result.
Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 43 40
Mean (Standard Deviation)
Unit of Measure: log10 (CFU/mL)
-2.842  (1.8552) -0.469  (1.3697)
2.Secondary Outcome
Title Change in S. Aureus Log CFU/mL From Baseline to Immediately Post-surgery
Hide Description 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.
Time Frame From baseline (day -10 to Day -1) to immediately post surgery (Day 0)
Hide Outcome Measure Data
Hide Analysis Population Description
microbiological Intent-To-Treat (micro ITT) set: all patients who were randomized, received at least 1 dose of study drug, have at least 1 post-baseline assessment of S. aureus log10 CFU/mL and who have a log10 CFU/mL result at baseline greater than 0, i.e. all patients in the mITT set with a quantifiable baseline microbiological result.
Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 43 40
Mean (Standard Deviation)
Unit of Measure: log10 (CFU/mL)
-2.773  (1.8531) -0.314  (1.7674)
3.Secondary Outcome
Title Change in S. Aureus Log CFU/mL From Baseline to 48 Hours After Surgery
Hide Description 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.
Time Frame From baseline to follow-up at 48 hours after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
microbiological Intent-To-Treat (micro ITT) set: all patients who were randomized, received at least 1 dose of study drug, have at least 1 post-baseline assessment of S. aureus log10 CFU/mL and who have a log10 CFU/mL result at baseline greater than 0, i.e. all patients in the mITT set with a quantifiable baseline microbiological result.
Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 43 40
Mean (Standard Deviation)
Unit of Measure: log10 (CFU/mL)
-2.700  (1.7362) -1.477  (1.6222)
4.Secondary Outcome
Title Change in S. Aureus Log CFU/mL From Baseline to Immediately After Surgery to 6 Days (± 24hours) After Surgery
Hide Description 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.
Time Frame From baseline to follow-up Day 6 ± 24hours after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
microbiological Intent-To-Treat (micro ITT) set: all patients who were randomized, received at least 1 dose of study drug, have at least 1 post-baseline assessment of S. aureus log10 CFU/mL and who have a log10 CFU/mL result at baseline greater than 0, i.e. all patients in the mITT set with a quantifiable baseline microbiological result.
Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 43 40
Mean (Standard Deviation)
Unit of Measure: log10 (CFU/mL)
-3.106  (1.7995) -2.399  (1.6933)
5.Secondary Outcome
Title Number of Participants With Staphylococcal Post-operative Infections During the 30-day Period After Surgery (90 Days in the Case of Foreign Implant)
Hide Description 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).
Time Frame From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant)
Hide Outcome Measure Data
Hide Analysis Population Description

Number of microITT patients with post-operative S.aureus infections

microbiological Intent-To-Treat (micro ITT) set: all patients who were randomized, received at least 1 dose of study drug, have at least 1 post-baseline assessment of S. aureus log10 CFU/mL and who have a log10 CFU/mL result at baseline greater than 0, i.e. all patients in the mITT set with a quantifiable baseline microbiological result.

Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 43 40
Measure Type: Number
Unit of Measure: participants
0 0
6.Secondary Outcome
Title Incidence of Treatment-emergent Adverse Events From the First Dose of Study Medication to 6 Days (± 24hours) After Last Dose of Study Medication.
Hide Description 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.
Time Frame Immediately prior to surgery until Day 6 ± 24hours.
Hide Outcome Measure Data
Hide Analysis Population Description

Total number of TEAEs in the safety set

Safety set: all patients who received at least 1 dose of study treatment

Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 63 61
Measure Type: Number
Unit of Measure: events
67 68
7.Secondary Outcome
Title Changes in Nasal Examination.
Hide Description 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.
Time Frame From Randomisation (Day -10 to Day -1) until 48hours ± 24hours post surgery.
Hide Outcome Measure Data
Hide Analysis Population Description

Number of patients in the safety set with clinically significant changes in nasal examination at 48h ± 24h

Safety set: all patients who received at least 1 dose of study drug

Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 63 61
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Changes in Brief Smell Identification Test (B-SIT).
Hide Description

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.

Time Frame From Randomisation (Day -10 to Day -1) until Day 6 ± 24hours post surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: all patients who received at least 1 dose of study drug
Arm/Group Title XF-73 Placebo
Hide Arm/Group Description:
Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

Overall Number of Participants Analyzed 63 61
Measure Type: Count of Participants
Unit of Measure: Participants
Assessed as 'Normal' at Day 6 ±24h post surgery
52
  82.5%
50
  82.0%
Assessed as 'Deficit relative to younger persons' at Day 6 ±24h post surgery
4
   6.3%
5
   8.2%
Assessed as 'Abnormal relative to age' at Day 6 ±24h post surgery
2
   3.2%
1
   1.6%
Assessed as 'Below percentile rank' at Day 6 ±24h post surgery
0
   0.0%
0
   0.0%
Assessed as 'Not Done' at Day 6 ±24h post surgery
0
   0.0%
3
   4.9%
Participants did not complete
5
   7.9%
2
   3.3%
Time Frame From screening until 7 days after a subject received first dose
Adverse Event Reporting Description

Non-treatment emergent AEs: recorded from the time when the patient is enrolled into the study until first administration of study drug, TEAEs: First Administration of Study Drug to Patient's Day 6 visit,

Only AEs that meet SAE criteria and are considered related with the study medication by the investigator will be recorded after Day 6 through the final follow up visit

 
Arm/Group Title XF-73 Placebo
Hide Arm/Group Description Participants received 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel 4 times in one day prior to surgery and once more after surgery, for a cumulative dose of 6.0 mg of XF-73.

Participants received 0.3 mL applications in each naris of placebo to match XF-73 nasal gel, 4 times in one day prior to surgery and once more after surgery.

Note: Placebo to match XF-73 nasal gel for colour and viscosity.

All-Cause Mortality
XF-73 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/63 (3.17%)      1/61 (1.64%)    
Hide Serious Adverse Events
XF-73 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/63 (6.35%)      5/61 (8.20%)    
Cardiac disorders     
Cardiac Arrest  1  0/63 (0.00%)  0 1/61 (1.64%)  1
Coronary artery occlusion  1  0/63 (0.00%)  0 1/61 (1.64%)  1
Angina unstable  1  1/63 (1.59%)  1 1/61 (1.64%)  1
Cardiogenic shock  1  1/63 (1.59%)  1 0/61 (0.00%)  0
Acute left ventricular failure  1  1/63 (1.59%)  1 0/61 (0.00%)  0
Cardiac tamponade  1  0/63 (0.00%)  0 1/61 (1.64%)  1
Infections and infestations     
Asymptomatic COVID-19  1  1/63 (1.59%)  1 0/61 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  0/63 (0.00%)  0 1/61 (1.64%)  1
Vascular disorders     
Hypotension  1  1/63 (1.59%)  1 0/61 (0.00%)  0
1
Term from vocabulary, MedDRA v23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
XF-73 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/63 (49.21%)      15/61 (24.59%)    
Blood and lymphatic system disorders     
Anaemia  1  5/63 (7.94%)  5 6/61 (9.84%)  6
Cardiac disorders     
Pericardial effusion  1  5/63 (7.94%)  5 5/61 (8.20%)  5
Atrial Fibrillation  1  5/63 (7.94%)  5 4/61 (6.56%)  6
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1  16/63 (25.40%)  16 14/61 (22.95%)  14
1
Term from vocabulary, MedDRA v23.1
Indicates events were collected by systematic assessment
Study recruitment was affected by the impact of the COVID-19 pandemic as hospitals and staff were reassigned to provide care needed to treat patients with COVID-19.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Protocol limits Investigators to not publish any data (poster, abstract, paper, etc.) without having consulted with the Sponsor in advance.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Project Manager
Organization: Destiny Pharma
Phone: +44 (0)1273-704440
EMail: info@destinypharma.com
Layout table for additonal information
Responsible Party: Destiny Pharma Plc
ClinicalTrials.gov Identifier: NCT03915470    
Other Study ID Numbers: XF-73B07
First Submitted: April 1, 2019
First Posted: April 16, 2019
Results First Submitted: March 24, 2022
Results First Posted: June 1, 2022
Last Update Posted: June 1, 2022