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

Phase 2

Terminated

• Conditions: Wound Heal; Wound Healing Disturbance of; Diabetic Foot Ulcer; Wound Healing Disorder; Wound Healing Delayed; Diabetic Foot Ulcer Mixed
• Interventions: Biological: Placebo; Biological: ILP100-Topical (emilimogene sigulactibac) 5x10^7 CFU/cm^2; Biological: ILP100-Topical (emilimogene sigulactibac) 1x10^9 CFU/cm^2

• Registration Number: NCT05608187
• Lead Sponsor: Ilya Pharma

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-26
• Study First Submitted: 2022-10-03
• Study First Submitted QC: 2022-10-31
• Study First Posted: 2022-11-08
• Primary Completion: 2024-12-16
• Study Completion: 2024-12-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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 (at or below the ankle) which fulfils all of the following criteria at Screening and at the time of Baseline:

  1. A non-interdigital wound
  2. Accessible for administration of IMP, wound study assessments and procedures
  3. Persistence of the wound for at least 6 weeks at Baseline
  4. Assessed by the investigator to be of non-venous etiology.
  5. Minimum full skin ulcer without undermining, with no exposed muscle, tendon or bone
  6. A wound area of 1.0 - 5.0 cm^2 after sharp or mechanical debridement at Screening
  7. 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, or at Screening expected by the Investigator to have a high probability for wound size changes within this range during this period.

• Toe pressure ≥20 mm Hg

• Expected to comply with the study procedures

Exclusion Criteria

• Infected index wound with clinical signs of inflammation at Screening or Baseline.
• 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 2 years
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
ILP100Lo	ILP100-Topical (emilimogene sigulactibac) 5x10^7 CFU/cm^2	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.
ILP100Hi	ILP100-Topical (emilimogene sigulactibac) 1x10^9 CFU/cm^2	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.

Primary Outcome Measures

Name	Time	Method
Compare incidence of serious adverse events (SAEs) between treatment groups	Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.	The incidence of SAEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.
Compare incidence of adverse events (AEs) between treatment groups	Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.	The incidence of AEs up to Week 26 will be presented for each treatment group and by category, causality, severity and frequency.

Secondary Outcome Measures

Name	Time	Method
Presence of viable L. reuteri containing the pSIP_CXCL12 plasmid in wounds	Compare up to Year 5 between the ILP100-Topical and Placebo treatment arms.	Bacteria will be collected from the wound and perilesional skin with sterile cotton swabs which will be cultured.
Local tolerability by Investigator's assessment	Compare Investigator's local tolerability assessments up to Week 26 between the ILP100-Topical and Placebo treatment arms.	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.
Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Independent Assessor's Assessment	Compare the ILP100-Topical and Placebo treatment arms up to Week 26.	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.
Proportion of subjects with recurrence of index wound	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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.
CXCL12 levels in plasma	Compare up to Week 16 between the ILP100-Topical and Placebo treatment arms.	CXCL12 levels in plasma as measured by enzyme-linked immunosorbent assay (ELISA).
Wound area reduction (percent of Baseline)	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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.
Proportion of subjects with ≥50% and 75% partially healed wounds	Compare ILP100-Topical and Placebo treatment arms up to Week 26	The proportion of subjects with ≥50% and 75% partially healed wounds will be calculated.
Time to partial (≥50% and 75%) and complete healing	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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 new wound infections	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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.	Compare the ILP100-Topical and Placebo treatment arms up to Year 5 after initiation of treatment.	AEs and SAEs will be recorded during annual visits from Year 1 through Year 5.
Wound healing rate	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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 completely healed wounds	Compare ILP100-Topical and Placebo treatment arms up to Week 26	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.
Local tolerability by Independent Assessor's assessment	Compare local tolerability up to Week 26 between the ILP100-Topical and Placebo treatment arms.	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	Compare the ILP100-Topical and Placebo treatment arms up to Week 26.	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.

Trial Locations

Locations (2)

Department of Endocrinology, Skåne University Hospital; 🇸🇪 Lund, Sweden

Clinical Diabetes Research Unit at Uppsala University Hospital; 🇸🇪 Uppsala, Sweden