Safety and Efficacy of HO/03/03 10μg in the Treatment of Plantar Neuropathic Diabetic Foot Ulcers

Study Overview
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Brief Summary
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A prospective, double blind, randomized, placebo controlled, outpatient, parallel group comparison trial to assess the safety and efficacy of HO/03/03 10µg versus Placebo, applied topically once daily for up to 14 weeks in at least 196 subjects diagnosed with Diabetes Mellitus and having a single target non-healing Plantar Neuropathic Diabetic Foot Ulcer.

Official Title
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Safety and Efficacy of HO/03/03 10μg in the Treatment of Plantar Neuropathic Diabetic Foot Ulcers (Truheal)

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Drug: HO/03/03 10µg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 80 years, extremes included Diagnosed with Diabetes Mellitus Type 1 or Type 2 Having a documented single target non-healing Plantar Neuropathic Diabetic Foot Ulcer with a minimal duration of 4 weeks prior to the informed consent signature Ulcer size at randomization: Wagner grade 1, between 2.0 cm2 to 10 cm2, extremes included or; Wagner grade 2, between 1.0 cm2 to 10 cm2, extremes included; Single target, ulcer on the study foot: Wagner grade 1 or; Wagner grade 2 (does not involve abscess or osteomyelitis); Target ulcer area decreased by ≤ 30% OR ≤ 0.1 cm/wk edge healing rate measured after debridement at screening to after debridement if clinically indicated at randomization. Glycosylated Haemoglobin A1c (HbA1c) ≤ 12%; Ankle to Brachial Index (ABI) on study foot: 0.7 ≤ ABI ≤ 1.2 or ABI > 1.2 and toe pressure > 50 mm Hg (ABI measured by Doppler; toe blood pressure measured by toe cuff); Diabetic Neuropathy is confirmed by neurological testing Subject should be available for the entire study period, and be able and willing to adhere to protocol requirements Subject has signed the informed consent form prior to any study protocol related procedure Exclusion Criteria: Subjects meeting one or more of the following criteria cannot be selected: Anamnesis of current or recent past (within the last 2 years) abuse of alcohol, barbiturates, benzodiazepines, amphetamines, narcotics, cocaine, psychoactive drugs or other abused substances that will interfere with treatment compliance Use of growth factors, skin graft or participation in an investigational study within the last 30 days prior to the beginning of the screening period Females who are pregnant, lactating, of child-bearing potential, or post-menopausal for less than 2 years and not using a medically approved method of contraception or females who test positive on a blood-based pregnancy test Have a documented medical history of HIV, HBV or HCV Have a documented medical history of a significant cardiac, pulmonary, gastrointestinal, endocrine (other than Diabetes Mellitus type 1 or 2), metabolic, neurological, hepatic or nephrologic disease and/or receiving dialysis Anaemia (Haemoglobin < 9 gram/dL for females or Haemoglobin < 10 gram/dL for males) or White Blood Cells count > 11,000/μL or Platelets count < 100,000/μL or impaired renal function (Creatinine > 3 mg/dL) or liver function tests > 3 times upper normal lab values or any indication of malnourishment (Albumin < 2.8 g/dL) or any other clinically significant biochemistry, haematology and urinalysis tests; Had any clinically significant illness during the last 4 weeks prior to the screening period; Have a current malignancy or a past malignancy in the last 5 years other than Basal Cell Carcinoma or is treated by radio/chemotherapy Have any signs of clinical infection in the wound (which could be linked to raised body temperature, abscess, osteomyelitis, necrosis or erythema) Had any antibiotic treatment during the screening period; Had evidence of infection or osteomyelitis on a plain foot x-ray at screening; Is bed-ridden or unable to come to the clinic; Have more than one target non-healing Diabetic Foot Ulcer per subject; Plantar Neuropathic DFU is located on an active Charcot foot; Have hind foot ulcer or have a foot deformity/condition preventing the use of offload footwear; Had a leg revascularization surgery within the last 6 months or be a candidate for revascularization surgery during the course of the study; Glucocorticosteroid treatment (Prednisone >10 mg/day or its equivalent) Inability to stop alternative wound healing treatment (e.g. Becaplermin or other topical products) following debridement

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HO/03/03 10µg<br> | Drug: HO/03/03 10µg<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete ulcer closure | Time to Event Analysis that determines time for incidence of 100% study wound closure per unit of time (days) and the incidence of 100% wound closure per unit of time using the log rank test. | Up to 14 weeks inclusive | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in wound area at 4 weeks |  | 4 weeks | 
| 75% wound closure by or on Study Week 14 |  | Up to 14 weeks inclusive | 
| Incidence of adverse events, changes in vital signs, physical examination, electrocardiogram and laboratory tests from baseline to termination. |  | 14 weeks | 
| Incidence of 100% Closure tested by the Fisher exact 2-tailed test |  | Up to 14 weeks inclusive | 
| Percent change in granulation tissue at 4 weeks |  | 4 weeks | 
| Incidence of improved ulcers |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Foot Ulcer, DFU, Wound healing