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

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

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.

Inclusion Criteria:

1. Age between 18 and 80 years, extremes included

2. Diagnosed with Diabetes Mellitus Type 1 or Type 2

3. 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

4. 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;

5. Single target, ulcer on the study foot:

   • Wagner grade 1 or;
   • Wagner grade 2 (does not involve abscess or osteomyelitis);

6. 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.

7. Glycosylated Haemoglobin A1c (HbA1c) ≤ 12%;

8. 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);

9. Diabetic Neuropathy is confirmed by neurological testing

10. Subject should be available for the entire study period, and be able and willing to adhere to protocol requirements

11. 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:

1. 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
2. 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
3. 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
4. Have a documented medical history of HIV, HBV or HCV
5. 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
6. 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;
7. Had any clinically significant illness during the last 4 weeks prior to the screening period;
8. Have a current malignancy or a past malignancy in the last 5 years other than Basal Cell Carcinoma or is treated by radio/chemotherapy
9. Have any signs of clinical infection in the wound (which could be linked to raised body temperature, abscess, osteomyelitis, necrosis or erythema)
10. Had any antibiotic treatment during the screening period;
11. Had evidence of infection or osteomyelitis on a plain foot x-ray at screening;
12. Is bed-ridden or unable to come to the clinic;
13. Have more than one target non-healing Diabetic Foot Ulcer per subject;
14. Plantar Neuropathic DFU is located on an active Charcot foot;
15. Have hind foot ulcer or have a foot deformity/condition preventing the use of offload footwear;
16. Had a leg revascularization surgery within the last 6 months or be a candidate for revascularization surgery during the course of the study;
17. Glucocorticosteroid treatment (Prednisone >10 mg/day or its equivalent)
18. Inability to stop alternative wound healing treatment (e.g. Becaplermin or other topical products) following debridement