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Evaluating Safety and Biological Effect on Wound Healing of ILP100-Topical in Subjects With Diabetic Foot Ulcers

Primary Purpose

Wound Heal, Wound Healing Disturbance of, Wound Healing Disorder

Status
Recruiting
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
ILP100-Topical (emilimogene sigulactibac) 5x10^7 CFU/cm^2
ILP100-Topical (emilimogene sigulactibac) 1x10^9 CFU/cm^2
Placebo
Sponsored by
Ilya Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wound Heal focused on measuring emilimogene sigulactibac, ILP100, ILP100-Topical, Lactobacillus reuteri, Limosilactobacillus reuteri, CXCL12, diabetic foot ulcer, wound healing, Ilya Pharma, live biopharmaceutical product, lactic acid bacteria

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed written informed consent Males and females aged ≥18 years Diagnosis of diabetes mellitus type 1 or 2 HbA1c ≤ 86 mmol/mol (≤ 10%) at Screening Subjects with at least one first time or recurrent full thickness ulcer (below the ankle) that fulfils all of the following criteria at Screening and at the time of Baseline: A non-interdigital wound Accessible for administration of IMP, wound study assessments and procedures Persistence of the wound for at least 6 weeks at Baseline Minimum full skin ulcer without undermining, with no exposed muscle, tendon or bone A wound area of 1.0 - 5.0 cm^2 after sharp or mechanical debridement at Screening During the 2-weeks between start of Run-in Phase and Baseline the wound size must not decrease by more than 30% or increase by more than 25%, which correspond to wound areas of 0.7 - 6.3 cm^2 Toe pressure ≥30 mm Hg Expected to comply with the study procedures Exclusion Criteria: Has any clinically infected diabetic foot ulcer at Screening and Baseline, confirmed by bacterial wound culture, or ongoing antibiotic treatment The index wound determined as heavily exuding defined as requiring more than 1 dressing change per day or requiring use of super absorbent dressing Wound duration longer than 1 year Active Charcot deformity of the study foot Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 Hemoglobin concentration <100 g/L at Baseline Planned or ongoing treatment with corticosteroids to an equivalent dose of prednisolone >10 mg per day or other immunosuppressive therapy, or such treatment within 4 weeks prior to Baseline Has any major surgery or hospitalization planned up to Week 26 Has changed a treatment for diabetes during the last 3 weeks before Baseline. Dose change is allowed Ongoing treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors Revascularization procedure in the index wound leg planned or undertaken within 8 weeks before Screening, or under investigation Current smokers Participation in other clinical studies or having received any investigational treatment within 1 month or at the earliest five times the half-life prior to Screening Has any disease conditions, including ulcerative dermatological disorders and vasculitis, or comorbidities which is expected to prevent the subject from participating in the study or confounding the evaluation of the safety profile and effect on wound healing of ILP100 Pregnant or lactating woman Male subjects not willing to use a condom and refrain from donating sperm Female subjects of childbearing potential unless they use a contraceptive method with a failure rate of < 1% to prevent pregnancy

Sites / Locations

  • Cordinator Medical Service ABRecruiting
  • Department of Endocrinology, Skåne University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

ILP100Lo

ILP100Hi

Placebo

Arm Description

During the Treatment Phase, subjects will continue on standard of care according to the protocol and ILP100Lo (ILP100-Topical, 5x10^7 colony forming units (CFU)/cm^2) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.

During the Treatment Phase, subjects will continue on standard of care according to the protocol and ILP100Hi (ILP100-Topical, 1x10^9 CFU/cm^2) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.

During the Treatment Phase, subjects will continue on standard of care according to the protocol and Placebo (ILP100 dilution buffer mixed with the activation peptide SppIP) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.

Outcomes

Primary Outcome Measures

Compare incidence of adverse events (AEs) between treatment groups
The incidence of AEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.
Compare incidence of serious adverse events (SAEs) between treatment groups
The incidence of SAEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.

Secondary Outcome Measures

Local tolerability by Investigator's assessment
Local tolerance to treatment will be assessed by the Investigator. Wound tolerability parameters will be presented in categories of appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Local tolerability by Independent Assessor's assessment
Local tolerance to treatment will be assessed by the Independent Assessor. Wound tolerability parameters will be presented in categories of appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Investigator's Assessment
The proportion of subjects with a local tolerability parameter grade ≥ 2 will be calculated (grading system=0 to 3, where 3 is severe). Local tolerance to treatment, infection and wound healing will be assessed by the Investigator. Wound tolerability parameters include appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Independent Assessor's Assessment
The proportion of subjects with a local tolerability parameter grade ≥ 2 will be calculated (grading system=0 to 3, where 3 is severe). Local tolerance to treatment, infection and wound healing will be assessed by the Independent Assessor. Wound tolerability parameters include appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Wound area reduction (percent of Baseline)
Wound area will be measured and calculated as proportion of the wound area at Baseline. Metric analyses of wound area is made on 3D models acquired up to Week 26.
Wound healing rate
Wound healing rate will be calculated as change in the wound area per week. Wound healing will be assessed by Investigators and Independent Assessor.
Proportion of subjects with ≥50% and 75% partially healed wounds
The proportion of subjects with ≥50% and 75% partially healed wounds will be calculated.
Time to partial (≥50% and 75%) and complete healing
Time to event outcomes will be evaluated using Kaplan-Meier curves. Wound healing is defined as full skin re-epithelialization without drainage or dressing requirements confirmed at two consecutive study visits 2 weeks apart. Wound healing will be assessed by Investigators and Independent Assessor.
Wound area
Wound area will be measured and calculated (cm^2). Metric analyses of wound healing, including area, are made using 3D models acquired Screening to Week 26. Wound measures will be automatically generated by a computer software and validated by the Independent Assessor.
Proportion of subjects with completely healed wounds
The proportion of subjects with completely healed wounds will be calculated. Wound healing is defined as full skin re-epithelialization without drainage or dressing requirements confirmed at two consecutive study visits 2 weeks apart. Wound healing will be assessed by Investigators and the Independent Assessor.
Proportion of subjects with recurrence of index wound
The proportion of subjects with recurrence of index wound will be calculated. For wound assessments after each index wound healing visit, it will be documented if the index wound is still healed or if any recurrence of the wound has occurred.
Proportion of subjects with new wound infections
The proportion of subjects with new wound infections will be calculated based on the Investigators evaluation of the skin, including assessing whether there are any new wound infections, at each study visit.
Days on antibiotic treatment
Days on antibiotic treatment as a percentage of days in the study up to Week 26 will be calculated for each subject.
Change in subject-reported wound-related pain
Change in wound-related pain in the area of the index wound, as reported by subjects, using a numeric rating scale (NRS; 0-10, where 10 is the worst possible pain).
Long-term incidence of AEs.
AEs and SAEs will be recorded during annual visits from Year 1 through Year 5.
CXCL12 levels in plasma
CXCL12 levels in plasma as measured by enzyme-linked immunosorbent assay (ELISA).
Presence of viable L. reuteri containing the pSIP_CXCL12 plasmid in wounds
Bacteria will be collected from the wound and perilesional skin with sterile cotton swabs which will be cultured.

Full Information

First Posted
October 3, 2022
Last Updated
October 31, 2022
Sponsor
Ilya Pharma
Collaborators
European Commission
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1. Study Identification

Unique Protocol Identification Number
NCT05608187
Brief Title
Evaluating Safety and Biological Effect on Wound Healing of ILP100-Topical in Subjects With Diabetic Foot Ulcers
Official Title
A Randomized, Double-Blind, Placebo-controlled, Parallel, Exploratory Phase 2a Study to Evaluate Safety and Biological Effect on Wound Healing of ILP100-Topical in Subjects With Diabetic Foot Ulcers
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 26, 2022 (Actual)
Primary Completion Date
December 2027 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ilya Pharma
Collaborators
European Commission

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A randomized, double-blind, placebo-controlled, parallel, exploratory phase 2a study to evaluate safety and biologic efficacy on wound healing of ILP100-Topical in subjects with diabetic foot ulcers during 26 weeks with a 5-year long-term follow-up period. A total of 30 subjects will be randomized to low dose of ILP100-Topical (ILP100Lo), high dose of ILP100-Topical (ILP100Hi) or Placebo according to a 1:1:1 randomization schedule. The study will consist of a 3-weeks Screening and Run-in Phase, followed by a 5-week Treatment Phase starting from Baseline and an Assessment Phase from Week 5 to Week 26. Thereafter, the subjects will be followed yearly during 5 years in a Long-Term Safety Follow-up Phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wound Heal, Wound Healing Disturbance of, Wound Healing Disorder, Wound Healing Delayed, Diabetic Foot Ulcer, Diabetic Foot Ulcer Mixed
Keywords
emilimogene sigulactibac, ILP100, ILP100-Topical, Lactobacillus reuteri, Limosilactobacillus reuteri, CXCL12, diabetic foot ulcer, wound healing, Ilya Pharma, live biopharmaceutical product, lactic acid bacteria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This is a double-blind study, and the allocation of treatments will not be disclosed to subjects, Investigator or Independent Evaluators until database lock after all subjects (who were not withdrawn) completed Week 26.
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ILP100Lo
Arm Type
Experimental
Arm Description
During the Treatment Phase, subjects will continue on standard of care according to the protocol and ILP100Lo (ILP100-Topical, 5x10^7 colony forming units (CFU)/cm^2) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.
Arm Title
ILP100Hi
Arm Type
Experimental
Arm Description
During the Treatment Phase, subjects will continue on standard of care according to the protocol and ILP100Hi (ILP100-Topical, 1x10^9 CFU/cm^2) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
During the Treatment Phase, subjects will continue on standard of care according to the protocol and Placebo (ILP100 dilution buffer mixed with the activation peptide SppIP) will be topically administered at two occasions on Day 1 (Baseline and Hour 2), Days 2, 3, and thereafter every second to third day until Day 31.
Intervention Type
Biological
Intervention Name(s)
ILP100-Topical (emilimogene sigulactibac) 5x10^7 CFU/cm^2
Other Intervention Name(s)
ILP100-Topical
Intervention Description
Topical application of ILP100-Topical (emilimogene sigulactibac) at a dose of 5x10^7 CFU/cm^2 wound area.
Intervention Type
Biological
Intervention Name(s)
ILP100-Topical (emilimogene sigulactibac) 1x10^9 CFU/cm^2
Other Intervention Name(s)
ILP100-Topical
Intervention Description
Topical application of ILP100-Topical (emilimogene sigulactibac) at a dose of 1x10^9 CFU/cm^2 wound area.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Topical application of placebo (ILP100 dilution buffer mixed with the activation peptide SppIP).
Primary Outcome Measure Information:
Title
Compare incidence of adverse events (AEs) between treatment groups
Description
The incidence of AEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Compare incidence of serious adverse events (SAEs) between treatment groups
Description
The incidence of SAEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Secondary Outcome Measure Information:
Title
Local tolerability by Investigator's assessment
Description
Local tolerance to treatment will be assessed by the Investigator. Wound tolerability parameters will be presented in categories of appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Time Frame
Compare Investigator's local tolerability assessments up to Week 26 between the ILP100-Topical and Placebo treatment arms.
Title
Local tolerability by Independent Assessor's assessment
Description
Local tolerance to treatment will be assessed by the Independent Assessor. Wound tolerability parameters will be presented in categories of appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Time Frame
Compare local tolerability up to Week 26 between the ILP100-Topical and Placebo treatment arms.
Title
Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Investigator's Assessment
Description
The proportion of subjects with a local tolerability parameter grade ≥ 2 will be calculated (grading system=0 to 3, where 3 is severe). Local tolerance to treatment, infection and wound healing will be assessed by the Investigator. Wound tolerability parameters include appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Time Frame
Compare the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Independent Assessor's Assessment
Description
The proportion of subjects with a local tolerability parameter grade ≥ 2 will be calculated (grading system=0 to 3, where 3 is severe). Local tolerance to treatment, infection and wound healing will be assessed by the Independent Assessor. Wound tolerability parameters include appearance of inflammation, amount of exudate present, hemorrhage, presence of slough/necrotic tissue, presence of granulation tissue and hypergranulation.
Time Frame
Compare the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Wound area reduction (percent of Baseline)
Description
Wound area will be measured and calculated as proportion of the wound area at Baseline. Metric analyses of wound area is made on 3D models acquired up to Week 26.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Wound healing rate
Description
Wound healing rate will be calculated as change in the wound area per week. Wound healing will be assessed by Investigators and Independent Assessor.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Proportion of subjects with ≥50% and 75% partially healed wounds
Description
The proportion of subjects with ≥50% and 75% partially healed wounds will be calculated.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Time to partial (≥50% and 75%) and complete healing
Description
Time to event outcomes will be evaluated using Kaplan-Meier curves. Wound healing is defined as full skin re-epithelialization without drainage or dressing requirements confirmed at two consecutive study visits 2 weeks apart. Wound healing will be assessed by Investigators and Independent Assessor.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Wound area
Description
Wound area will be measured and calculated (cm^2). Metric analyses of wound healing, including area, are made using 3D models acquired Screening to Week 26. Wound measures will be automatically generated by a computer software and validated by the Independent Assessor.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Proportion of subjects with completely healed wounds
Description
The proportion of subjects with completely healed wounds will be calculated. Wound healing is defined as full skin re-epithelialization without drainage or dressing requirements confirmed at two consecutive study visits 2 weeks apart. Wound healing will be assessed by Investigators and the Independent Assessor.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Proportion of subjects with recurrence of index wound
Description
The proportion of subjects with recurrence of index wound will be calculated. For wound assessments after each index wound healing visit, it will be documented if the index wound is still healed or if any recurrence of the wound has occurred.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Proportion of subjects with new wound infections
Description
The proportion of subjects with new wound infections will be calculated based on the Investigators evaluation of the skin, including assessing whether there are any new wound infections, at each study visit.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Days on antibiotic treatment
Description
Days on antibiotic treatment as a percentage of days in the study up to Week 26 will be calculated for each subject.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Change in subject-reported wound-related pain
Description
Change in wound-related pain in the area of the index wound, as reported by subjects, using a numeric rating scale (NRS; 0-10, where 10 is the worst possible pain).
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 26
Title
Long-term incidence of AEs.
Description
AEs and SAEs will be recorded during annual visits from Year 1 through Year 5.
Time Frame
Compare the ILP100-Topical and Placebo treatment arms up to Year 5 after initiation of treatment.
Title
CXCL12 levels in plasma
Description
CXCL12 levels in plasma as measured by enzyme-linked immunosorbent assay (ELISA).
Time Frame
Compare up to Week 16 between the ILP100-Topical and Placebo treatment arms.
Title
Presence of viable L. reuteri containing the pSIP_CXCL12 plasmid in wounds
Description
Bacteria will be collected from the wound and perilesional skin with sterile cotton swabs which will be cultured.
Time Frame
Compare up to Year 5 between the ILP100-Topical and Placebo treatment arms.
Other Pre-specified Outcome Measures:
Title
Proportion of subjects with index limb amputation and any limb amputation
Description
The proportion of subjects with index limb amputation and any limb amputation will be calculated.
Time Frame
Compare at Week 26, and thereafter annually Year 1 to 5, between the ILP100-Topical and Placebo treatment arms.
Title
All-cause mortality and index wound-related mortality
Description
Mortality data will be acquired from the patient's medical records.
Time Frame
Compare at Week 26, and thereafter annually Year 1 to 5, between the ILP100-Topical and Placebo treatment arms.
Title
Quality of life assessed with Wound-Quality of Life (Wound QoL) questionnaire
Description
Quality of life will be assessed by the subjects using the Wound-QoL questionnaire including 17 questions on impairment related to the wound, each to be answered by grades from 0-4 (0='not at all' to 4='very much')
Time Frame
Compare up to Week 16 between the ILP100-Topical and Placebo treatment arms.
Title
Time for IMP preparation
Description
Time needed for IMP preparation, by the study personnel, will be recorded.
Time Frame
Compare at Week 4 between the ILP100-Topical and Placebo treatment arms.
Title
Total number of redressings, off-loading and devices used for the treatment of the index wound
Description
Wound management will include redressing, which will be done both during home visits and study site visits, while debridement and changes of off-loading devices should only be done at study site visits. The total number of redressings, off-loading and devices used for the treatment of the index wound will be recorded.
Time Frame
Compare the ILP100-Topical and Placebo treatment arms during 16 weeks from baseline.
Title
Wound volume
Description
Metric analyses of wound healing, including volume, are made using 3D models acquired from Screening to Week 26. Wound measures will be automatically generated by a computer software and validated by the Independent Assessor.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Wound depth
Description
Metric analyses of wound healing, including depth, are made using 3D models acquired from Screening to Week 26. Wound measures will be automatically generated by a computer software and validated by the Independent Assessor.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Wound volume reduction (percent of Baseline)
Description
Reduction of wound volume (percent of Baseline) will be calculated. Metric analyses of wound healing, including volume, are made using 3D models acquired from Screening to Week 26. Wound measures will be automatically generated by a computer software and validated by the Independent Assessor.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Wound depth reduction (percent of Baseline)
Description
Reduction of wound depth (percent of Baseline) will be calculated. Metric analyses of wound healing, including depth, are made using 3D models acquired from Screening to Week 26. Wound measures will be automatically generated by a computer software and validated by the Independent Assessor.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Analyses of predictive factors for wound healing outcome
Description
Analyses of associations between baseline clinical (including toe pressure at Baseline and sex) and biologic characteristics (including wound size and pH) with wound healing outcomes through Week 26. A statistical regression model will be developed to predict wound healing up to Week 26
Time Frame
Analyses of associations between baseline clinical and biologic characteristics and wound healing outcomes up to Week 26.
Title
Analyses of predictive factors for occurence of AEs
Description
Analyses of associations between baseline clinical (including toe pressure at Baseline and sex) and biologic characteristics (including wound size and pH) with AEs. A statistical regression model will be developed to predict the AE outcome up to Week 26
Time Frame
Analyses of associations between baseline clinical and biologic characteristics and occurence of AEs up to Week 26.
Title
Analyses of scar area
Description
Scar area will be measured for the index wound using 3D models generated from superimposing 2D images and infrared scanning of the topography of the wound and perilesional skin acquired at the study visits.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Analyses of scar volume
Description
Scar volume will be measured for the index wound using 3D models generated from superimposing 2D images and infrared scanning of the topography of the wound and perilesional skin acquired at the study visits.
Time Frame
Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Title
Change from Baseline in level of wound pH
Description
Change from Baseline in level of wound pH will be measured on exuding wounds (at the discretion of the Investigator) at selected timepoints just prior to IMP administration using sterile litmus paper strips.
Time Frame
Compare at Weeks 1, 4, 5, 8 and 16 between the ILP100-Topical and Placebo treatment arms.
Title
Change from Baseline in local blood flow in wound area measured with Laser Speckle Contrast Analysis
Description
Change from Baseline in local blood flow around the index wound will be addressed by non-invasive imaging using Laser Speckle Contrast Analysis (LASCA) where each wound and surrounding skin will be recorded for at least one minute of stable recording at selected timepoints in the study.
Time Frame
Compare ILP100-Topical and Placebo treatment arms up to Week 16
Title
Pathogenic wound bacteria characterization upon clinically defined or suspicions of wound infection
Description
Characteristics of ILP100 will be addressed by collecting bacteria from the wound with sterile cotton swabs which will be cultured.
Time Frame
Compare species of infection-causing wound pathogens up to Week 26 between the ILP100-Topical and Placebo treatment arms.
Title
Wound microbiome profile, including presence and proportion of wound pathogenic bacteria
Description
The impact of ILP100 on the wound microbiome composition will be assessed from wounds swabs identified by sequencing bacterial 16S ribosomal ribonucleic acid (rRNA) genes.
Time Frame
Compare the microbiome profile up to Week 16 between the ILP100 and Placebo treatment arms.
Title
Presence of anti-drug antibodies (ADA) to CXCL12 and the activation peptide SppIP up to Year 5
Description
The development of anti-drug antibodies (ADAs, to CXCL12 and SppIP) as measured by electrochemiluminescence immunoassay (ECLIA).
Time Frame
Compare presence of ADA up to Year 5 between the ILP100-Topical and Placebo treatment arms.
Title
Analysis of L. reuteri containing the pSIP_CXCL12 plasmid in blood, feces, and perilesional skin
Description
Shedding to the external environment will be measured in feces and water lock samples collected at the sites. The method will determine the number of live L. reuteri R2LC containing pSIP_CXCL12 in the samples. Used dressings will also be collected for shedding analyses of L. reuteri R2LC containing the pSIP_CXCL12 plasmid.
Time Frame
Analyses of presence of L. reuteri containing the pSIP_CXCL12 plasmid up to Year 5.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed written informed consent Males and females aged ≥18 years Diagnosis of diabetes mellitus type 1 or 2 HbA1c ≤ 86 mmol/mol (≤ 10%) at Screening Subjects with at least one first time or recurrent full thickness ulcer (below the ankle) that fulfils all of the following criteria at Screening and at the time of Baseline: A non-interdigital wound Accessible for administration of IMP, wound study assessments and procedures Persistence of the wound for at least 6 weeks at Baseline Minimum full skin ulcer without undermining, with no exposed muscle, tendon or bone A wound area of 1.0 - 5.0 cm^2 after sharp or mechanical debridement at Screening During the 2-weeks between start of Run-in Phase and Baseline the wound size must not decrease by more than 30% or increase by more than 25%, which correspond to wound areas of 0.7 - 6.3 cm^2 Toe pressure ≥30 mm Hg Expected to comply with the study procedures Exclusion Criteria: Has any clinically infected diabetic foot ulcer at Screening and Baseline, confirmed by bacterial wound culture, or ongoing antibiotic treatment The index wound determined as heavily exuding defined as requiring more than 1 dressing change per day or requiring use of super absorbent dressing Wound duration longer than 1 year Active Charcot deformity of the study foot Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 Hemoglobin concentration <100 g/L at Baseline Planned or ongoing treatment with corticosteroids to an equivalent dose of prednisolone >10 mg per day or other immunosuppressive therapy, or such treatment within 4 weeks prior to Baseline Has any major surgery or hospitalization planned up to Week 26 Has changed a treatment for diabetes during the last 3 weeks before Baseline. Dose change is allowed Ongoing treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors Revascularization procedure in the index wound leg planned or undertaken within 8 weeks before Screening, or under investigation Current smokers Participation in other clinical studies or having received any investigational treatment within 1 month or at the earliest five times the half-life prior to Screening Has any disease conditions, including ulcerative dermatological disorders and vasculitis, or comorbidities which is expected to prevent the subject from participating in the study or confounding the evaluation of the safety profile and effect on wound healing of ILP100 Pregnant or lactating woman Male subjects not willing to use a condom and refrain from donating sperm Female subjects of childbearing potential unless they use a contraceptive method with a failure rate of < 1% to prevent pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andreas Fasth, PhD
Phone
+46 (0) 704 663110
Email
andreas.fasth@ilyapharma.se
First Name & Middle Initial & Last Name or Official Title & Degree
Evelina Vågesjö, PhD/MBA
Phone
+46 (0) 706 366494
Email
evelina.vagesjo@ilyapharma.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan Apelqvist, MD/PhD
Organizational Affiliation
Department of Endocrinology, Skåne University Hospital, Malmö, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cordinator Medical Service AB
City
Linköping
ZIP/Postal Code
587 58
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Wilhems, MD/PhD
Facility Name
Department of Endocrinology, Skåne University Hospital
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Magnus Löndahl, MD/PhD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Undecided due to ongoing development.
Citations:
PubMed Identifier
29432190
Citation
Vagesjo E, Ohnstedt E, Mortier A, Lofton H, Huss F, Proost P, Roos S, Phillipson M. Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):1895-1900. doi: 10.1073/pnas.1716580115. Epub 2018 Feb 5.
Results Reference
background
PubMed Identifier
30870037
Citation
Ohnstedt E, Lofton Tomenius H, Vagesjo E, Phillipson M. The discovery and development of topical medicines for wound healing. Expert Opin Drug Discov. 2019 May;14(5):485-497. doi: 10.1080/17460441.2019.1588879. Epub 2019 Mar 14.
Results Reference
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PubMed Identifier
35213962
Citation
Ohnstedt E, Lofton Tomenius H, Frank P, Roos S, Vagesjo E, Phillipson M. Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria. Pharmaceutics. 2022 Jan 19;14(2):229. doi: 10.3390/pharmaceutics14020229.
Results Reference
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Evaluating Safety and Biological Effect on Wound Healing of ILP100-Topical in Subjects With Diabetic Foot Ulcers

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