Safety and Tolerability of Single and Multiple Doses of SoftOx Biofilm Eradicator (SBE) in Chronic Leg Wounds
- Conditions
- Chronic Leg UlcerVenous Leg Ulcer
- Interventions
- Drug: SoftOx Biofilm Eradicator (Groups 1 to 7)Device: Sterile isotonic saline (Groups 1 to 4)
- Registration Number
- NCT05710094
- Lead Sponsor
- SoftOx Solutions AS
- Brief Summary
Single-centre clinical study investigating the safety and tolerability of randomised, double-blinded, placebo-controlled ascending single doses of topically applied SoftOx Biofilm Eradicator (SBE) in patients with chronic leg wounds and of open-label once daily, twice daily, and thrice daily dosing of topically applied SBE for five days in patients with chronic leg wounds. The primary objective of the study is to assess the safety and tolerability of single and multiple doses of topically applied SBE in patients with chronic leg wounds. A secondary objective of the study is to assess changes in bacterial burden in the leg wound after treatment with SBE.
- Detailed Description
The study enrolled subjects with chronic leg wounds, i.e., the intended target population for SBE.
The first part of the study aimed to identify the highest tolerated dose of SBE in a randomised, double-blind, and placebo-controlled manner with sequential evaluation of 4 single ascending doses. As a precaution, sentinel and staggered dosing was applied in the single-dose groups: the safety of two subjects treated on two different days (at least one of whom was treated with SBE) was reviewed before commencing dosing of the remaining subjects in a single-dose group (sentinel dosing), with an interval of at least 1 hour between the dosing of different subjects (staggered dosing). The starting dose of 500 µg/mL HOCl + 1% HAc was based on previous knowledge concerning the MIC and MBC of SBE and the results obtained in a 28-day, repeated-dose toxicology study in minipigs. The latter indicated that up to 1000 µg/mL + 3% HAc (the highest dose tested) was well-tolerated. Choosing 500 µg/mL HOCl + 1% HAc as the starting dose in the current study provided a safety factor of 2 for HOCl and a safety factor of 3 for HAc. The highest well-tolerated dose of SBE in the non-clinical toxicology study was chosen as the highest single dose to be evaluated in the current study. Dose-escalation steps in the single-dose groups were conservatively defined with escalation factors ranging from 1 to 2. Prior to dose escalation, blinded results were evaluated by the Safety Monitoring Committee (SMC).
The second part of the study aimed to evaluate the safety and tolerability of multiple dosing of SBE. The multiple-dose groups tested different dosing regimens with formulations determined by the SMC based on the safety and tolerability of the formulations evaluated in the first part of the study. Three multiple-dose groups (once-, twice-, and thrice-daily administrations) were planned.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 3 SoftOx Biofilm Eradicator (Groups 1 to 7) Single dose of 500ppm HOCl + 3 % HAc, or placebo Group 2 Sterile isotonic saline (Groups 1 to 4) Single dose of 500ppm HOCl + 2 % HAc, or placebo Group 3 Sterile isotonic saline (Groups 1 to 4) Single dose of 500ppm HOCl + 3 % HAc, or placebo Group 2 SoftOx Biofilm Eradicator (Groups 1 to 7) Single dose of 500ppm HOCl + 2 % HAc, or placebo Group 6 SoftOx Biofilm Eradicator (Groups 1 to 7) Multiple doses (BID for 5 days) of xppm HOCl + x% HAc# Group 4 Sterile isotonic saline (Groups 1 to 4) Single dose of 1000ppm HOCl + 3 % HAc, or placebo Group 1 Sterile isotonic saline (Groups 1 to 4) Single dose of 500ppm HOCl + 1 % HAc, or placebo Group 4 SoftOx Biofilm Eradicator (Groups 1 to 7) Single dose of 1000ppm HOCl + 3 % HAc, or placebo Group 1 SoftOx Biofilm Eradicator (Groups 1 to 7) Single dose of 500ppm HOCl + 1 % HAc, or placebo Group 7 SoftOx Biofilm Eradicator (Groups 1 to 7) Multiple doses (TID for 5 days) of xppm HOCl + x% HAc# Group 5 SoftOx Biofilm Eradicator (Groups 1 to 7) Multiple doses (OD for 5 days) of xppm HOCl + x% HAc#
- Primary Outcome Measures
Name Time Method Nature, occurrence, and severity of adverse events (AEs) From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP Clinically significant abnormal values of vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, body temperature), safety blood and urine parameters, ECG, and physical examination will be reported as AEs.
Change from baseline in wound pain assessed by use of visual analogue scale (VAS). From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP Change from baseline i.e., the last value before the (first) administration of IMP, in wound pain as assessed by use of a 10 cm VAS, where 0 cm indicated no pain at all, and 10 cm indicated the worst imaginable pain at the time of assessment.
- Secondary Outcome Measures
Name Time Method Change from baseline in wound bacterial burden (number of colony-forming units per mL; CFU/mL) From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP The bacterial burden of wounds was assessed using surface swabs (collected with the Z technique) at baseline, i.e., before the first administration of IMP, 20 min after the administration of IMP (on the treatment day for the single-dose groups, on each day of treatment for the OD multiple-dose group and after the second administration on each day of treatment for the BID multiple-dose group) and at the Follow-up visit.
Trial Locations
- Locations (1)
Bispebjerg University Hospital
🇩🇰Copenhagen, Denmark
Bispebjerg University Hospital🇩🇰Copenhagen, Denmark