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

NCT05608187 | Terminated Phase 2 DMC

• 2 other identifiers: IP-CT-0032021-000563-69
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 between the ILP100-Topical and Placebo treatment arms up to Week 26.

• 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.

  Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.

Secondary Outcomes (17)

• 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 tolerability by Independent Assessor's assessment

  Compare local tolerability up to Week 26 between the ILP100-Topical and Placebo treatment arms.

• 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.

• 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.

• Wound area reduction (percent of Baseline)

  Compare ILP100-Topical and Placebo treatment arms up to Week 26

Other Outcomes (19)

• Proportion of subjects with index limb amputation and any limb amputation

  Compare at Week 26, and thereafter annually Year 1 to 5, between the ILP100-Topical and Placebo treatment arms.

• All-cause mortality and index wound-related mortality

  Compare at Week 26, and thereafter annually Year 1 to 5, between the ILP100-Topical and Placebo treatment arms.

• Quality of life assessed with Wound-Quality of Life (Wound QoL) questionnaire

  Compare up to Week 16 between the ILP100-Topical and Placebo treatment arms.

Study Arms (3)

ILP100Lo

EXPERIMENTAL

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.

Biological: ILP100-Topical (emilimogene sigulactibac) 5x10^7 CFU/cm^2

ILP100Hi

EXPERIMENTAL

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.

Biological: ILP100-Topical (emilimogene sigulactibac) 1x10^9 CFU/cm^2

Placebo

PLACEBO COMPARATOR

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.

Biological: Placebo

Interventions

ILP100-Topical (emilimogene sigulactibac) 5x10^7 CFU/cm^2 BIOLOGICAL

Topical application of ILP100-Topical (emilimogene sigulactibac) at a dose of 5x10\^7 CFU/cm\^2 wound area.

Also known as: ILP100-Topical

ILP100Lo

ILP100-Topical (emilimogene sigulactibac) 1x10^9 CFU/cm^2 BIOLOGICAL

Topical application of ILP100-Topical (emilimogene sigulactibac) at a dose of 1x10\^9 CFU/cm\^2 wound area.

Also known as: ILP100-Topical

ILP100Hi

Placebo BIOLOGICAL

Topical application of placebo (ILP100 dilution buffer mixed with the activation peptide SppIP).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• Assessed by the investigator to be of non-venous etiology.
• 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, 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ilya Pharma: lead
• European Commission: collaborator

Study Sites (2)

Department of Endocrinology, Skåne University Hospital

Lund, 221 85, Sweden

Location

Clinical Diabetes Research Unit at Uppsala University Hospital

Uppsala, Sweden

Location

Related Publications (3)

• 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.

  PMID: 29432190 BACKGROUND

• 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.

  PMID: 30870037 BACKGROUND

• 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.

  PMID: 35213962 BACKGROUND

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Jan Apelqvist, MD/PhD

  Department of Endocrinology, Skåne University Hospital, Malmö, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: November 8, 2022
• Study Start: September 26, 2022
• Primary Completion: December 16, 2024
• Study Completion: December 20, 2024
• Last Updated: March 5, 2025

Record last verified: 2025-03

Locations

SE (2)