Chronic Leg UlcerPhase 1NCT05710094
Safety and Tolerability of Single and Multiple Doses of SoftOx Biofilm Eradicator (SBE) in Chronic Leg Wounds
A Phase 1 study testing SoftOx Biofilm Eradicator (Groups 1 to 7) and Sterile isotonic saline (Groups 1 to 4) in people with Chronic Leg Ulcer and Venous Leg Ulcer, run by SoftOx Solutions AS at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Leg Ulcer, Venous Leg Ulcer
- What is being tested?
- SoftOx Biofilm Eradicator (Groups 1 to 7) and Sterile isotonic saline (Groups 1 to 4)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteDenmark
- Study dates
- 19 Oct 2021to 19 Aug 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible for this study, patients must fulfil all of the following criteria:
- Male and female patients aged 18 and above at time of informed consent.
- Chronic (present for at least 4 weeks) leg wound, as judged by the Investigator, with a size of at least 1 cm2 and maximally 100 cm2 (measured as the width x length) on the day of the (first) administration of IMP.
- Patients must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
Who cannot join
- Patients are not eligible for this study if they fulfil any of the following exclusion criteria:
- Any surgical or medical condition, including findings in the medical history or in the pre-study assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the patient in the study or that could interfere with the study objectives, conduct, or evaluation at screening or time of the (first) administration of IMP.
- Known or clinical suspicion of cancer in the leg wound at screening or time of the (first) administration of IMP, e.g., basal cell carcinoma or squamous cell carcinoma.
- Clinical symptoms of COVID-19 or positive test for SARS-CoV-2 (testing according to local procedures) at screening or on the day of the (first) administration of IMP.
- Clinical infection requiring systemic antibiotics at time of the (first) administration of IMP.
- Severe ischaemia in the target leg at screening or time of the (first) administration of IMP defined as an ankle brachial index (ABI) < 0.5.
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- Necrotic tissue in leg wound at time of the (first) administration of IMP.
- Clinically significantly reduced perception of sensation or pain assessed in proximity of the wound at screening.
- A pain score from the leg wound above 4 assessed on a 10 cm VAS , where 0 cm indicates no pain at all and 10 cm indicates the worst imaginable pain at time of the (first) administration of IMP.
- Use of opioids from time of screening to end of study, unless used a at stable dose, as judged by the Investigator.
- Participation in the treatment phase of a clinical study with an investigational new drug within 30 days or 5 half-lives (whichever is longer) before the (first) administration of IMP.
- Has previously received SBE in any of the concentrations tested in the current study.
- Pregnant or lactating at screening or time of the (first) administration of IMP.
- Ascertained or presumptive allergy/ hypersensitivity to any components of the IMP; history of anaphylaxis to drugs or serious allergic reactions leading to hospitalisation or any other allergy reaction in general, which the Investigator considers may affect the safety of the patient and/or outcome of the study.
- Inability to communicate or cooperate with the Investigator (e.g., language problems, illiteracy, poor mental status) or to comply with the requirements of the study.
- Other factors which in the opinion of the Investigator may interfere with study conduct.
- Legal incapacity or limited legal capacity.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
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.
Read the 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
- Being tested
- SoftOx Biofilm Eradicator (Groups 1 to 7), Sterile isotonic saline (Groups 1 to 4)
- Keywords
- lower extremities infection biofilm antimicrobial
- Medical subject headings
- Varicose Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SoftOx Biofilm Eradicator (Groups 1 to 7)Drug
Also called SS0350
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.
Sterile isotonic saline (Groups 1 to 4)Device
Also called Irriflex
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
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Single dose of 500ppm HOCl + 1 % HAc, or placebo Receives: Drug: SoftOx Biofilm Eradicator (Groups 1 to 7); Device: Sterile isotonic saline (Groups 1 to 4) |
| Group 2 | Experimental | Single dose of 500ppm HOCl + 2 % HAc, or placebo Receives: Drug: SoftOx Biofilm Eradicator (Groups 1 to 7); Device: Sterile isotonic saline (Groups 1 to 4) |
| Group 3 | Experimental | Single dose of 500ppm HOCl + 3 % HAc, or placebo Receives: Drug: SoftOx Biofilm Eradicator (Groups 1 to 7); Device: Sterile isotonic saline (Groups 1 to 4) |
| Group 4 | Experimental | Single dose of 1000ppm HOCl + 3 % HAc, or placebo Receives: Drug: SoftOx Biofilm Eradicator (Groups 1 to 7); Device: Sterile isotonic saline (Groups 1 to 4) |
| Group 5 | Experimental | Multiple doses (OD for 5 days) of xppm HOCl + x% HAc# Receives: Drug: SoftOx Biofilm Eradicator (Groups 1 to 7) |
| Group 6 | Experimental | Multiple doses (BID for 5 days) of xppm HOCl + x% HAc# Receives: Drug: SoftOx Biofilm Eradicator (Groups 1 to 7) |
| Group 7 | Experimental | Multiple doses (TID for 5 days) of xppm HOCl + x% HAc# Receives: Drug: SoftOx Biofilm Eradicator (Groups 1 to 7) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nature, occurrence, and severity of adverse events (AEs)
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.
Measured: From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP
Change from baseline in wound pain assessed by use of visual analogue scale (VAS).
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.
Measured: From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP
Secondary outcomes (1)
Change from baseline in wound bacterial burden (number of colony-forming units per mL; CFU/mL)
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.
Measured: From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2023
- Study start19 Oct 2021
- Primary completion19 Aug 2022
- Study completion19 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Leg UlcerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised, double-blinded, placebo-controlled ascending single dose groups (Groups 1 to 4); followed by open-label multiple ascending dose groups (Groups 5 to 7)
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- SoftOx Solutions AS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Peick Sonne, MD; PhD, Principal investigator, Bispebjerg and Frederiksberg HospitalGlenn Gundersen, PhD, Study director, SoftOx Solutions A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05710094
- Sponsor's protocol ID
- SBE-01
- Status last verified
- Jan 2023
- First submitted
- 18 Oct 2021
- Last updated
- 2 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT05710094
- Acronym / sponsor ID
- SBE-01
- Conditions
- Chronic Leg Ulcer, Venous Leg Ulcer
- Keywords
- lower extremities infection biofilm antimicrobial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- SoftOx Solutions ASIndustry (pharma, biotech, devices)
- Study start
- 19 Oct 2021 (actual)
- Primary completion
- 19 Aug 2022 (actual)
- Study completion
- 19 Aug 2022 (actual)
- First posted
- 2 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 7
- Model description
- Randomised, double-blinded, placebo-controlled ascending single dose groups (Groups 1 to 4); followed by open-label multiple ascending dose groups (Groups 5 to 7)
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: SoftOx Biofilm Eradicator (Groups 1 to 7), Device: Sterile isotonic saline (Groups 1 to 4)Single dose of 500ppm HOCl + 1 % HAc, or placebo |
| Group 2 | Experimental | Drug: SoftOx Biofilm Eradicator (Groups 1 to 7), Device: Sterile isotonic saline (Groups 1 to 4)Single dose of 500ppm HOCl + 2 % HAc, or placebo |
| Group 3 | Experimental | Drug: SoftOx Biofilm Eradicator (Groups 1 to 7), Device: Sterile isotonic saline (Groups 1 to 4)Single dose of 500ppm HOCl + 3 % HAc, or placebo |
| Group 4 | Experimental | Drug: SoftOx Biofilm Eradicator (Groups 1 to 7), Device: Sterile isotonic saline (Groups 1 to 4)Single dose of 1000ppm HOCl + 3 % HAc, or placebo |
| Group 5 | Experimental | Drug: SoftOx Biofilm Eradicator (Groups 1 to 7)Multiple doses (OD for 5 days) of xppm HOCl + x% HAc# |
| Group 6 | Experimental | Drug: SoftOx Biofilm Eradicator (Groups 1 to 7)Multiple doses (BID for 5 days) of xppm HOCl + x% HAc# |
| Group 7 | Experimental | Drug: SoftOx Biofilm Eradicator (Groups 1 to 7)Multiple doses (TID for 5 days) of xppm HOCl + x% HAc# |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female patients aged 18 and above at time of informed consent.
- Chronic (present for at least 4 weeks) leg wound, as judged by the Investigator, with a size of at least 1 cm2 and maximally 100 cm2 (measured as the width x length) on the day of the (first) administration of IMP.
- Patients must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
Key exclusion criteria (17 listed)
- Patients are not eligible for this study if they fulfil any of the following exclusion criteria:
- Any surgical or medical condition, including findings in the medical history or in the pre-study assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the patient in the study or that could interfere with the study objectives, conduct, or evaluation at screening or time of the (first) administration of IMP.
- Known or clinical suspicion of cancer in the leg wound at screening or time of the (first) administration of IMP, e.g., basal cell carcinoma or squamous cell carcinoma.
- Clinical symptoms of COVID-19 or positive test for SARS-CoV-2 (testing according to local procedures) at screening or on the day of the (first) administration of IMP.
- Clinical infection requiring systemic antibiotics at time of the (first) administration of IMP.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SoftOx Biofilm Eradicator (Groups 1 to 7)Also: SS0350SBE 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. | Drug | Group 1, Group 2, Group 3, Group 4, Group 5, Group 6, Group 7 |
| Sterile isotonic saline (Groups 1 to 4)Also: IrriflexSterile 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 | Device | Group 1, Group 2, Group 3, Group 4 |
Primary outcome
Nature, occurrence, and severity of adverse events (AEs)
Time frame: 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).
Time frame: 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.
1 secondary outcome
Change from baseline in wound bacterial burden (number of colony-forming units per mL; CFU/mL)
Time frame: From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Peick Sonne, MD; PhD principal investigator
Bispebjerg and Frederiksberg Hospital
Glenn Gundersen, PhD study director
SoftOx Solutions A/S
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SoftOx Biofilm Eradicator (Groups 1 to 7) and Sterile isotonic saline (Groups 1 to 4) in people with Chronic Leg Ulcer and Venous Leg Ulcer, run by SoftOx Solutions AS at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nature, occurrence, and severity of adverse events (AEs) (time frame: From the start of the first administration of IMP to 3 to 5 days after the last administration of IMP). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2023.