NCT05710094

Safety and Tolerability of Single and Multiple Doses of SoftOx Biofilm Eradicator (SBE) in Chronic Leg Wounds

Single-centre, Randomised, Double-blinded, Placebo-controlled Ascending Single Doses of SoftOx Biofilm Eradicator (SBE) and Open-label Once-, Twice-, and Thrice-daily Dosing of SBE for Five Days in Patients With Chronic Leg Wounds.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: SoftOx Solutions AS · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Chronic Leg Ulcer
• Venous Leg Ulcer

Interventions

Type	Name	Description
DRUG	SoftOx Biofilm Eradicator (Groups 1 to 7)	SBE is a water-based formulation containing hypochlorous acid (HOCl) at concentrations of 500-1000 µg/mL and acetic acid (HAc) at concentrations of 1-3 %. Both active ingredients are naturally occurring molecules and have a long history of safe use in medicinal products and in solutions approved as medical devices. Both molecules, exhibit broad-spectrum antimicrobial activity at the concentrations present in SBE. The antimicrobial effect of HOCl is rapid and powerful by acting on and disrupting the function of key microbial molecules such as proteins, lipids, and nucleic acids, while remaining safe to mammalian cells and not promoting the emergence of new resistant microbes. Moreover, HOCl is active against biofilms, and some studies suggest that HOCl may also increase oxygenation of the wound site leading to improved healing.
DEVICE	Sterile isotonic saline (Groups 1 to 4)	Sterile isotonic saline was used as placebo because it is part of standard of care, used as an irrigation solution at dressing change and has the same appearance as SBE

Timeline

• Start date: 2021-10-19
• Primary completion: 2022-08-19
• Completion: 2022-08-19
• First posted: 2023-02-02
• Last updated: 2023-02-02

Locations

1 site across 1 country: Denmark