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Trial registered on ANZCTR

Registration number

ACTRN12623000056695

Ethics application status

Approved

Date submitted

22/12/2022

Date registered

17/01/2023

Date last updated

6/07/2024

Date data sharing statement initially provided

17/01/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Proof of concept study of RECCE®327 topical anti-infective therapy for mild skin and soft tissue diabetes foot infections (DFIs)

Scientific title

Proof of concept study of RECCE®327 topical anti-infective therapy for mild skin and soft tissue diabetes foot infections (DFIs)

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1272-4334

Trial acronym

RECCE® 327-101 PoC-DFI

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Diabetes-related foot infection

Condition category

Condition code

Infection

Studies of infection and infectious agents

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The topical "spray-on" formulation of RECCE®327 solution is a pale-yellow colour, has a pH of 7.1 and contains polyacrolein polyethene glycol oligomers 4.76% [polyethylene glycol (PEG) 200 (56.20%), water (39%), the active oligomer (4.76%; 7.80% TM001), acrolein monomer (0.189ppm) and conjugated carbonyls (1.15 ABS @ 230 nm, & 0.75 ANS @ 272nm). The technique for topical delivery of RECCE®327 solution is quick, simple and does not require hospitalisation.

It is anticipated that less than 1mL of RECCE®327 solution will be required to saturate the wound bed. The number on mL (to 1 decimal place) will be recorded. We do not envisage that there will be ulcers of significant size requiring the dispensing of >1mL of RECCE®327 solution. The wound will be left open until visibly dry for at least 5 minutes (whichever is first) before it is covered with a standard foam dressing. This is to ensure that there is adequate absorption of the topical preparation into the wound bed and to prevent immediate uptake into dressings.

Cohort 1 (16 participants) will receive spray-on RECCE®327 daily over a 14-day study period whilst Cohort 2 (16 participants) will receive spray-on RECCE®327 every two days during a 14-day study period.

Appropriate participants will be identified in the High Risk Foot Clinic by the research podiatrist and other members of the study team. This will be their initial appointment or "day 0". Procedures including the removal of dressings, irrigation, debridement, preparation, and application of the topical RECCE®327 and re-dressing will occur and should take approximately 30 minutes. This represents a typical consultation time for HRFS patients, however the number of visits required over the study duration are more than "standard care" (i.e. removal of dressings, wound cleansing, conservative sharps debridement of non-viable wound bed tissue and periwound tissue, appropriate selection of dressings and pressure offloading with chairside devices, prefabricated foot orthoses, post-operative wound shoes, knee-high walkers etc.)

The study team will dispense a weeks' supply of RECCE®327 solution in a cooler bag with a temperature tracker on the day of recruitment and day 7 or the midpoint of the study. The amount dispensed will depend on treatment cohort allocation:
- Baseline - Daily application cohort: 5x 10mL vials of topical RECCE®327 solution.
- Baseline - Second-daily application cohort: 2x 10mL vials of topical RECCE®327 solution.
- Day 7/ midpoint - Daily application cohort: 6x 10mL vials of topical RECCE®327 solution.
- Day 7/ midpoint - Second-daily application cohort: 3x 10mL vials of topical RECCE®327 solution.
Vials must then be refrigerated by the participant in their home between 2°C-8°C.

A study nurse will attend the patient's home for daily or second daily application of topical RECCE®327 solution, depending on treatment cohort allocation. They will perform the following procedures:
- Removal of dressings and irrigation of wound with sodium chloride 0.9%
- Application of the topical RECCE®327 and re-dressing of wound
- Record keeping for study and medicolegal purposes
Each visit should take approximately 30 minutes and is representative of a typical home-visiting nurse follow up, however the number of visits required over the study duration are more than that of "standard care". At each visit, participants will be assessed for treatment-related adverse effects which can be escalated to the study team. The volume of RECCE®327 applied per cm2 will also be recorded.

Participants will be monitored in the High Risk Foot Clinic at Liverpool Hospital face-to-face on days 7 and 14 of the trial. During these visits, topical therapy will be re-applied and standard wound care (as above) will be provided. Participants will be assessed for treatment-related adverse effects and the volume of RECCE®327 applied per cm2 will be recorded. Daily or second daily home-nursing reviews will allow the study team to quickly detect deterioration and escalate matters if required.

The requirement for rescue therapy will be be assessed at each review (clinic or home-nursing). Home-visiting nurses would need to escalate this matter to the study team and an urgent clinic visit would need to be arranged. The mainstay rescue therapy would be cessation of the study drug with escalation to the appropriate systemic antimicrobial therapy. Rescue therapy may be required if there are signs of increasing infection severity, determined by the International Working Group on the Diabetic Foot (IWGDF) DFI classification as; increasing erythema, inflammation, increasing wound dimensions and/or poorer tissue quality (necrosis), involvement of deeper anatomical structures (bone, joint, tendon etc), presence of systemic signs of infection (fever, rigors etc.), increased leukocytosis and an increase in other inflammatory markers through adjunctive pathology. Rescue therapy may also be required at the end of the treatment period (14 days) where a member of the study team determines that the DFI is resolving (improvement in clinical markers and DFI score), but a clinical cure is not achieved (DFI resolution).

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Cohort 2 (16 participants) will receive spray-on RECCE®327 every two days over a 14-day study period. This form of treatment (cohort 2) with dressing changes every two days more closely corresponds to usual clinical practice than a daily dressing change.

Control group

Dose comparison

Outcomes

Primary outcome [1]

This is a composite outcome as it each part is assessed as a change in score:
Change in diabetic foot wound scores as assessed using the Diabetic Foot Infection Wound Scoring Scale and the Wound, Ischaemia and foot Infection (WIfI) classification:
1. Number of participants demonstrating DFI resolution as assessed by a change in score of the Diabetic Foot Infection Wound Scoring Scale and the Wound, Ischaemia and foot Infection (WIfI) classification.
2. Number of participants demonstrating healing as assessed by a change in score of the Diabetic Foot Infection Wound Scoring Scale and the Wound, Ischaemia and foot Infection (WIfI) classification.

Timepoint [1]

Baseline/ day 0 of commencement of spray-on RECCE®327 solution, day 3 post-commencement of spray-on RECCE®327 solution, day 7 post-commencement of spray-on RECCE®327 solution, day 10 post-commencement of spray-on RECCE®327 solution day 14, day 21 post-commencement of spray-on RECCE®327 solution, and day 28 post-commencement of spray-on RECCE®327 solution.

Primary outcome [2]

Number of participants requiring rescue therapy (escalation to appropriate systemic antimicrobial therapy), as assessed by either:
1. Signs of increasing infection severity and a change in infection score (WIfI), including increasing erythema, inflammation, enlargement of the ulcer with increased appearance of necrotic tissue, involvement of deeper anatomical structures, presence of systemic manifestations such as fever or rigors and increased leukocytosis and other inflammatory markers through adjunctive pathology.
2. Participant has completed 14 days of study treatment and infected ulcer is resolving (improvement in Diabetic Foot Infection Wound Scoring Scale and the Wound, Ischaemia and foot Infection (WIfI) classification) but a clinical cure has not been achieved (DFI resolution).
The requirement for rescue therapy will be assessed by the research podiatrist and team during face-to-face visits and reported subjectively by patient during telehealth reviews.

Timepoint [2]

Primary outcome [3]

(This is a composite outcome)
Describe local and/or systemic changes in:
1. Participant clinical status that might suggest toxicity
2; Diabetic foot ulcer that might suggest toxicity
Both factors will be assessed by the research podiatrist and team during face-to-face visits and reported subjectively by patient during telehealth reviews.
(There have been no adverse effects or events reports in topical application to infected burn wounds in a Phase I/II clinical trial for the treatment of acute burn wound infections at the Fiona Stanley Hospital, WA. Patients have only subjectively reported minor, brief stinging as the solution contacts the infected area, however this is quite common in therapeutic activity on wound surfaces and has been noted to diminish in line with reduction in bacterial loads on the wound, confirmed by wound culture.)

Timepoint [3]

Secondary outcome [1]

Presence or absence of wound pathogens as determined by standard microbiological analysis of tissue wound specimens obtained after treatment for likely pathogens of infection

Timepoint [1]

Within 18 months of study commencement.

Secondary outcome [2]

(This is a composite secondary outcome):
Rates of treatment failure as assessed by:
1. A change in score of the Diabetic Foot Infection Wound Scoring Scale and the Wound, Ischaemia and foot Infection (WIfI) classification.
2. Clinical signs of infection progression (greater than 2 signs or symptoms of infection substantially worsening (i.e. increasing erythema, inflammation, enlargement of the ulcer with increased appearance of necrotic tissue, involvement of deeper anatomical structures, presence of systemic manifestations such as fever or rigors and increased leukocytosis and other inflammatory markers through adjunctive pathology)), or;
3. A requirement for rescue therapy to alter therapy: to a broader spectrum antibiotic; or to switch from oral to parenteral therapy; or to any unplanned additional antibiotic therapy, surgery or hospitalization required to control the index DFI.

All factors will be assessed by the research podiatrist and team during face-to-face visits and reported subjectively by patient during telehealth reviews.

Timepoint [2]

Secondary outcome [3]

(This is a composite secondary outcome as all components will be analysed together).
Changes in laboratory results demonstrating clinical outcomes and drug safety: full blood count; renal and liver function tests; serum inflammatory markers; microbiologic results of cultures; and antibiotic sensitivities.

Timepoint [3]

Baseline/ day 0 of commencement of spray-on RECCE®327 solution, day 7 post-commencement of spray-on RECCE®327 solution, day 14 post-commencement of spray-on RECCE®327 solution.

Secondary outcome [4]

Number of participants demonstrating healing using the Diabetic Foot Infection Wound Scoring Scale and the Wound, Ischaemia and foot Infection (WIfI) classification. (this is an additional primary outcome)

Timepoint [4]

Eligibility

Key inclusion criteria

1. Wound – Grade 1 (excluding bone involvement or exposed deep structures)
2. Ischemia – Grade 0 – 2
3. Foot Infection – Grade 1; This represents the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) Classification System and Score 2 /Infectious Diseases Society of America (IDSA) Score Mild DFI
AND
4. Aged > 18 years
5. Presence of either type 1 or type 2 diabetes mellitus
6. Newly diagnosed (<14 days) infective signs or symptoms with no use of systemic or topical antimicrobial/antibiotic therapy 72-hours (3 days) prior to enrolment.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Using WIfI the study exclusion criteria are:
- Wound – Grade 0, 2 or 3, or wound with exposed bone or deep structures
- Ischemia – Grade 3
- Foot Infection – Grade 0, 2 or 3; This represents PEDIS 1, 3 or 4 / IDSA uninfected or moderate or severe DFI
AND
- Participants with chronic infective symptoms who have received multiple (>2) antibiotic regimens within the previous 4 weeks or greater;
- Proof of underlying bone involvement (osteomyelitis) based on; imaging (plain X-ray, CT or MRI), clinical examination (exposed bone or positive probe to bone test) or culture/histopathology of a bone specimen;
- DRFU < 1cm in surface area;
- Aged < 18 years;
- Documented peripheral arterial disease with ankle brachial indices = 0.4 or toe brachial indices < 0.5 or toe pressure < 40 mmHg;
- Pregnant women, women desiring pregnancy within the duration of the study or those unwilling to practice contraception, women who are breast feeding;
- Known allergy to any components of the RECCE®327 solution or any of its excipients, including polyethylene glycol (PEG) 200, the active oligomer, acrolein monomer, or conjugated carbonyls.
- Otherwise assessed by study investigators as unsuitable to take tissue via biopsy or unable to follow trial protocols.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Eligible patients who are consented for the study will be allocated by opening, in sequence, a sealed envelope containing details of the allocation.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

The sequence of envelopes will be available in the Clinic. They will have been prepared by a research team member not involved in recruitment, using Sealed Envelope free software with block sizes of 2 and 4 to generate the randomised list.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 1 / Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Statistical analysis will be descriptive providing details of the clinical characteristics and microbiology of the infected wounds as well as the outcomes (clinical or toxicity) at the end of treatment, and after 2 weeks. Analysis of the primary outcome will be conducted using all participants that have received at least one dose of the study drug. Pre-defined sub-group analysis will consider the daily and every second day dosing interval groups separately. We consider a desirable outcome to be at least 80% complete response, which would be clinically comparable (equivalent) to the outcome from oral systemic antibiotic therapy.

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Other reasons/comments

Other reasons

Study Principal Investigator is retiring and the site has been unable to source an appropriate substitute PI. The study therefore has to terminate earlier than originally anticipated.

Date of first participant enrolment

Anticipated

1/08/2023

Actual

9/08/2023

Date of last participant enrolment

Anticipated

Actual

30/11/2023

Date of last data collection

Anticipated

Actual

2/01/2024

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Liverpool Hospital - Liverpool

Recruitment postcode(s) [1]

2170 - Liverpool

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Recce Pharmaceuticals

Address [1]

Head Office - Sydney
Level 25, 88 Phillip Street
Aurora Place
SYDNEY NSW 2000
AUSTRALIA

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Recce Pharmaceuticals

Address

Head Office - Sydney
Level 25, 88 Phillip Street
Aurora Place
SYDNEY NSW 2000
AUSTRALIA

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Liverpool Hospital (High Risk Foot Service)

Address [1]

Corner Elizabeth and Goulburn Streets, Liverpool NSW 2170

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry HREC

Ethics committee address [1]

 123 Glen Osmond Road
Eastwood SA 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

06/12/2022

Ethics approval number [1]

2022/ETH00769

Summary

Brief summary

This is a Phase I/II proof-of-concept study of RECCE®327 topical anti-infective therapy for mild skin and soft tissue diabetes foot infections (DFIs). It is designed to establish effect size, patient tolerability and ease of use of a topical application in an ambulatory sample of patients. 

The study has been designed to provide proof of concept regarding the effect and tolerability of the study drug. We hypothesise that this will provide pilot data to guide sample size for future trials in the same patient group using the same assessment tools.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Hugh Dickson

Address

Liverpool Hospital
Corner of Elizabeth and Goulburn Streets
LIVERPOOL NSW 2170

Country

Australia

Phone

+61 2 8738 8089

Fax

+61 2 8738 7975

[email protected]

Contact person for public queries

Name

Amanda Carr

Address

Recce Pharmaceuticals
Head Office: Level 25, 88 Phillip Street, Aurora Place, Sydney, NSW. 2000

Country

Australia

Phone

+61 8 9362 9863

Fax

[email protected]

Contact person for scientific queries

Name

Hugh Dickson

Address

Liverpool Hospital
Corner of Elizabeth and Goulburn Streets
LIVERPOOL NSW 2170

Country

Australia

Phone

+61 2 8738 8089

Fax

+61 2 8738 7975

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically