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.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Nature, occurrence, and severity of adverse events (AEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Blinding and unblinding procedures applied only to the single-dose groups, i.e., Groups 1-4, randomized to receive SBE (active) or sterile saline (placebo).
The computer-generated randomisation list was kept strictly confidential, accessible only to authorised persons, until the time of unblinding of the study.
The following procedures were implemented in the single-dose groups to minimise the risk of unintended unblinding:
i. Blinded staff prepared the patient's leg wound for the administration of IMP.
ii. Both patient and blinded staff applied a nose clip, prior to and during IMP administration, until all materials used for the treatment (plastic wrapping, gauze, gallipot, etc.) had been removed and the room had been vented for a couple of minutes by opening a window.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group 1
Single dose of 500ppm HOCl + 1 % HAc, or placebo
干预措施: SoftOx Biofilm Eradicator (Groups 1 to 7) (Drug)
Group 1
Single dose of 500ppm HOCl + 1 % HAc, or placebo
干预措施: Sterile isotonic saline (Groups 1 to 4) (Device)
Group 4
Single dose of 1000ppm HOCl + 3 % HAc, or placebo
干预措施: Sterile isotonic saline (Groups 1 to 4) (Device)
Group 2
Single dose of 500ppm HOCl + 2 % HAc, or placebo
干预措施: SoftOx Biofilm Eradicator (Groups 1 to 7) (Drug)
Group 2
Single dose of 500ppm HOCl + 2 % HAc, or placebo
干预措施: Sterile isotonic saline (Groups 1 to 4) (Device)
Group 3
Single dose of 500ppm HOCl + 3 % HAc, or placebo
干预措施: SoftOx Biofilm Eradicator (Groups 1 to 7) (Drug)
Group 3
Single dose of 500ppm HOCl + 3 % HAc, or placebo
干预措施: Sterile isotonic saline (Groups 1 to 4) (Device)
Group 4
Single dose of 1000ppm HOCl + 3 % HAc, or placebo
干预措施: SoftOx Biofilm Eradicator (Groups 1 to 7) (Drug)
Group 5
Multiple doses (OD for 5 days) of xppm HOCl + x% HAc#
干预措施: SoftOx Biofilm Eradicator (Groups 1 to 7) (Drug)
Group 6
Multiple doses (BID for 5 days) of xppm HOCl + x% HAc#
干预措施: SoftOx Biofilm Eradicator (Groups 1 to 7) (Drug)
Group 7
Multiple doses (TID for 5 days) of xppm HOCl + x% HAc#
干预措施: SoftOx Biofilm Eradicator (Groups 1 to 7) (Drug)
结局指标
主要结局
Nature, occurrence, and severity of adverse events (AEs)
时间窗: 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).
时间窗: 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.
次要结局
- 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)