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

Phase 2TerminatedNCT05608187

Ilya Pharma1 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Wound Heal Wound Healing Disturbance of Wound Healing Disorder Wound Healing Delayed

Interventions

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

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

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

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

PlaceboBIOLOGICAL

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

Secondary Outcomes

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.

Time frame: 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

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.

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.

Time frame: 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

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.

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.