| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Diabetic Foot Ulcers |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10012664 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To determine the efficacy of Dermal – LSR plus Standard of Care (SOC) for the treatment of chronic diabetic foot ulcers (DFUs) in comparison to treatment with SOC alone.
To determine the safety of Dermal – LSR plus SOC for the treatment of chronic DFUs in comparison to treatment with SOC alone. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects may be included in the study only if they meet ALL of the following criteria:
1. Subject or legal guardain/representative has signed a written informed consent form prior to the first study intervention.
2. Subject is ≥18 and < 85 years old at the time the informed consent form is signed.
3. Subject has only one or more diatbetic ulcers on the target limb, with only one ulcer marked for study (target ulcer). The target ulcer must be no less than 4 cm from a non-target ulcer and in the investigator's opinion, be unlikely to coalesce with another ulcer within 12 weeks from randomization.
4. The target ulcer must have all of the following characteristics:
a. Plantar ulcers (fore and mid foot only, including lateral ulcers);
b. Grade 2 per Curative Health Services Classification (full thickness and subcutaneous tissues) i.e., extends through the dermis but without tendon, muscule, capsule or bone exposure;
c. Non-infected as determined by clinical assessment; where diagonsis of mild infection is characterized by the presence of two or more signs of inflammation (e.g., purulence (pus), erythema, pain, tenderness, warmth, and induration) with cellulitis/erythema extending ≤ 2 cm around the ulcer and is limited to the skin or superficial subcutaneous tissues. Additionally, there are no other local complications or evidence of systemic illness.
Providing that all other eligibility criteria are met, all subjects clinically assessed as non-infected at their baseline visit will be randomized and permittted to receive their assigned treatment.
● A sample of the debrided wound bed will be taken by curettage for quantitative analysis.
d. Neuropathic as determined by monofilament assessment;
e. Non-malignant as determined by radiologic examination and, if malignancy is suspected, confirmed by histological assessment;
f. Area ≥1.0 cm2 and ≤ 25.0 cm2 post-debridement;
g. Has been present for at least 8 weeks at the time of randomization, with the ulcer being under a physician's observation for at least 2 weeks prior to randomization.
5. Subject has been diagnosed with Type I or Type II Diabetes Mellitus and has an HbA1C value in the range of 6% to 10%.
6. Subject has a maxmium fasting blood glucose level of 13.8 mmol/L (245 mg/dL).
7. Subject has an ankle-brachial systolic pressure index between 0.7 and 1.3. If the value is > 1.3, then a transcutaneous partial pressure of oxygen (TcPO2) of ≥ 40 mmHg OR a toe pressure of ≥ 50 mmHg must be obtained for subject to be eligible.
8. Subject, if female and of childbearing potential, has a negative serum pregnancy test prior to randomization and is neither breastfeeding nor intending to become pregnant during the course of the study and agrees to use effective contraception (oral or dermal contraceptives, approved implant or IUD) for the duration of the study, OR has undergone tubal ligation, hysterectomy or is post-menopausal (no menses for a period of 12 months).
9. Subject is able and willing to attend the scheduled visits and to comply with the study procedures. |
|
| E.4 | Principal exclusion criteria |
Subjects will be excluded from the study for ANY of the following reasons:
1. Known or suspected disease of the immune system currently under investigation, other than Diabetes Mellitus.
2. Active or untreated malignancy or active, uncontrolled connective tissue disease.
3. Treatment with immunosuppressive or chemotherapeutic agents, radiotherapy or systemic corticosteroids less than 30 days before enrolment.
4. Presence of necrosis, purulence or sinus tracts that cannot be removed by debridement.
5. Has undergone a revascularization procedure aimed at increasing blood flow in the treatment target limb < 4 weeks prior to enrolment.
6. Active febrile illness (fever ≥ 38.0 °C p.o.).
7. Subject screening laboratory values outside the following ranges:
● Chemistry of AST, ALT and ALP: > 3x the normal upper limit
● Chemistry of serum creatinine: > 2x the normal upper limit
8. Osteomyelitis, as confirmed by radionuclide bone scan.
9. Presence of an active Charcot as determined by the clinical examination (new local pain, evidence of swelling and warmth).
10. Use of any topical treatments, other than SOC, in or on the surface of the target ulcer at the time of enrolment.
11. Enrolment in any investigational clinical trial within 30 days of the screening visit.
12. Knwon or suspected hypersensitivity to any study product components.
13. Recent or current history of alcohol or drug abuse.
14. Any condition, which in the opinion of the Investigator, would interfere with the evaluation of the study product or poses a health risk to the subject.
15. All site personnel directly affiliated with this study and their immediate families (immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Outcome:
• Complete ulcer closure by week 12
Secondary Efficacy Outcomes:
• Complete ulcer closure by week 20
• Time to achieve complete ulcer closure
• Rate of ulcer healing
• Relative ulcer area from baseline to week 20
• Recurrence of target ucler post closure to week 20
Safety Endpoints:
Safety assessments will include the incidence of adverse events, adverse reactions, immediate reactions, local and systemic reactions, osteomyelitis, ulcer infection, amputations and serious adverse events/unanticipated adverse device effects.
The potential for the development of an immune response to Dermal-LSR will be evaluated at the end of the study on retained serum samples collected at study entry and during the study period. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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