Clinical trial NCT05608187: 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
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Ilya Pharma
Sponsor class: INDUSTRY
Collaborators: name: European Commission
First posted: 2022-11-08
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 (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

Primary outcomes:
measure: Compare incidence of adverse events (AEs) between treatment groups
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Compare incidence of serious adverse events (SAEs) between treatment groups
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
Secondary outcomes:
measure: Local tolerability by Investigator's assessment
timeFrame: Compare Investigator's local tolerability assessments up to Week 26 between the ILP100-Topical and Placebo treatment arms.
measure: Local tolerability by Independent Assessor's assessment
timeFrame: Compare local tolerability up to Week 26 between the ILP100-Topical and Placebo treatment arms.
measure: Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Investigator's Assessment
timeFrame: Compare the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Proportion of subjects with a local tolerability parameter Grade ≥ 2 per Independent Assessor's Assessment
timeFrame: Compare the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Wound area reduction (percent of Baseline)
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Wound healing rate
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Proportion of subjects with ≥50% and 75% partially healed wounds
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Time to partial (≥50% and 75%) and complete healing
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Wound area
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Proportion of subjects with completely healed wounds
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Proportion of subjects with recurrence of index wound
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Proportion of subjects with new wound infections
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Days on antibiotic treatment
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Change in subject-reported wound-related pain
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 26
measure: Long-term incidence of AEs.
timeFrame: Compare the ILP100-Topical and Placebo treatment arms up to Year 5 after initiation of treatment.
measure: CXCL12 levels in plasma
timeFrame: Compare up to Week 16 between the ILP100-Topical and Placebo treatment arms.
measure: Presence of viable L. reuteri containing the pSIP_CXCL12 plasmid in wounds
timeFrame: Compare up to Year 5 between the ILP100-Topical and Placebo treatment arms.
Other outcomes:
measure: Proportion of subjects with index limb amputation and any limb amputation
timeFrame: Compare at Week 26, and thereafter annually Year 1 to 5, between the ILP100-Topical and Placebo treatment arms.
measure: All-cause mortality and index wound-related mortality
timeFrame: Compare at Week 26, and thereafter annually Year 1 to 5, between the ILP100-Topical and Placebo treatment arms.
measure: Quality of life assessed with Wound-Quality of Life (Wound QoL) questionnaire
timeFrame: Compare up to Week 16 between the ILP100-Topical and Placebo treatment arms.
measure: Time for IMP preparation
timeFrame: Compare at Week 4 between the ILP100-Topical and Placebo treatment arms.
measure: Total number of redressings, off-loading and devices used for the treatment of the index wound
timeFrame: Compare the ILP100-Topical and Placebo treatment arms during 16 weeks from baseline.
measure: Wound volume
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Wound depth
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Wound volume reduction (percent of Baseline)
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Wound depth reduction (percent of Baseline)
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Analyses of predictive factors for wound healing outcome
timeFrame: Analyses of associations between baseline clinical and biologic characteristics and wound healing outcomes up to Week 26.
measure: Analyses of predictive factors for occurence of AEs
timeFrame: Analyses of associations between baseline clinical and biologic characteristics and occurence of AEs up to Week 26.
measure: Analyses of scar area
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Analyses of scar volume
timeFrame: Compare between the ILP100-Topical and Placebo treatment arms up to Week 26.
measure: Change from Baseline in level of wound pH
timeFrame: Compare at Weeks 1, 4, 5, 8 and 16 between the ILP100-Topical and Placebo treatment arms.
measure: Change from Baseline in local blood flow in wound area measured with Laser Speckle Contrast Analysis
timeFrame: Compare ILP100-Topical and Placebo treatment arms up to Week 16
measure: Pathogenic wound bacteria characterization upon clinically defined or suspicions of wound infection
timeFrame: Compare species of infection-causing wound pathogens up to Week 26 between the ILP100-Topical and Placebo treatment arms.
measure: Wound microbiome profile, including presence and proportion of wound pathogenic bacteria
timeFrame: Compare the microbiome profile up to Week 16 between the ILP100 and Placebo treatment arms.
measure: Presence of anti-drug antibodies (ADA) to CXCL12 and the activation peptide SppIP up to Year 5
timeFrame: Compare presence of ADA up to Year 5 between the ILP100-Topical and Placebo treatment arms.
measure: Analysis of L. reuteri containing the pSIP_CXCL12 plasmid in blood, feces, and perilesional skin
timeFrame: Analyses of presence of L. reuteri containing the pSIP_CXCL12 plasmid up to Year 5.
Locations:
city: Lund
country: Sweden
facility: Department of Endocrinology, Skåne University Hospital
city: Uppsala
country: Sweden
facility: Clinical Diabetes Research Unit at Uppsala University Hospital
Study officials:
affiliation: Department of Endocrinology, Skåne University Hospital, Malmö, Sweden
name: Jan Apelqvist, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.