Diabetic neuropathic ulcer (DFU) MedDRA version: 21.1 Level: LLT Classification code 10012664 Term: Diabetic foot ulcer System Organ Class: 100000004858
Conditions
Interventions
Product Name: allo-APZ2-DFU
Product Code: allo-APZ2-DFU
Pharmaceutical Form: Cutaneous suspension
Current Sponsor code: T202-3
Other descriptive name: Allogeneic skin-derived ABCB5-positive mesenchyma
Sponsors
RHEACELL GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 18 to 85 years; 2. Patients with an existing diagnosis of diabetic mellitus Type 2, evaluated by blood test [HbA1c] 40 mmHg or doppler ultrasonography (at the discretion of the investigator) to exclude significant arterial diseases and critical limb ischemia, and a diabetic neuropathy test using a 128 Hz vibration tuning fork according to Rydel-Seiffer (as described by Guideline ”Nationale Versorgungsleitlinie - Neuropathie bei Diabetes im Erwachsenenalter”). If the ABI is >1.3, an additional doppler ultrasonography must be performed to exclude a PAOD masked by media sclerosis; 4. At Screening Visit 1 and 2 the wound surface area of the target ulcer should be between 1 and 50 cm² measured by using a scaled measuring sensor in combination with digital image analysis; 5. The ulcer’s surface area should be (mostly) free from callus or necrotic tissue; 6. If patients are suffering from two or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of healthy tissue from other ulcers; 7. Patients are willing and able to wear therapeutic shoes that are especially designed for patients with a diabetic neuropathic foot; 8. Body mass index (BMI) between 20 and 45 kg/m²; 9. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure; 10. Women of childbearing potential must have a negative blood pregnancy test at Visit 1; 11. Women of childbearing potential must be willing to use highly effective contraceptive methods during the course of the clinical trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: 1. Presence of acute Charcot foot; 2. Clinical signs of active osteomyelitis in the last three months; 3. Active wet gangrenous tissue; 4. Infection of the target ulcer requiring treatment as judged clinically; 5. Presence of an ulcer Grade =3 according to Wagner on the same foot as target ulcer; 6. Patients who are currently receiving dialysis; 7. Peripheral arterial occlusive disease (PAOD) including claudication with need of treatment; 8. Ulcers due to non-diabetic etiology; 9. Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to IMP application; 10. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis; 11. Any chronic dermatological disorders diagnosed at the investigator’s discretion; 12. Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound; 13. Treatment of target wound with active wound care agents (e.g. iruxol, local antibiotics or silver dressings), which have not been stopped 14 days before IMP application; 14. Any malignancy within the past 5 years, excluding successfully treated carcinoma in situ, basal cell carcinoma or squamous cell carcinoma of the skin without evidence of metastases; 15. Current use of steroid medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent); 16. Known abuse of alcohol, drugs, or medicinal products; 17. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol; 18. Pregnant or lactating women; 19. Patients infected with the human immunodeficiency virus (HIV 1&2); 20. Any known allergies to components of the IMP or concomitant medication; 21. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial; 22. Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient’s compliance, or place the patient at high risk of complications related to the treatment; 23. Employees of the sponsor, or employees or relatives of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction of DFUs) and safety (by monitoring adverse events) of two doses of allo-APZ2-DFU topically administered to the wound matrix of patients with diabetic neuropathic ulcer.;Secondary Objective: Not applicable.;Primary end point(s): 1. Primary efficacy endpoint: Percentage of wound surface area reduction at Week 12, or last available post-baseline measurement of Weeks 4, 6 or 8, if the Week 12 measurement is missing (last observation carried forward [LOCF]). 2. Primary safety endpoint: Adverse events. ;Timepoint(s) of evaluation of this end point: 1. Week 12, or last available post-baseline measurement of Weeks 4, 6 or 8, if the Week 12 measurement is missing. 2. During all patient visits except screening. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: 1. Percentage of wound surface area reduction; 2. Percentage of invisible and visible wound surface area reduction; 3. Absolute wound surface area reduction; 4. Absolute invisible and visible wound surface area reduction 5. Assessment of wound infection; 6. Time to first complete wound closure; 7. Proportion of patients achieving complete wound closure; 8. Time to first 30% reduction of wound surface area; 9. Proportion of patients achieving 30% reduction of wound surface area; 10. Assessment of wound exudation, epithelialization and formation of granulation tissue; 11. Time to amputation at target leg until Week 12; 12. Pain assessment as per numerical rating scale (NRS); 13. Assessment of Quality of life (QoL) using the short form 36 (SF-36) questionnaire; 14. Assessment of Dermatology-specific QoL based on the Dermatology Life Quality Index (DLQI) questionnaire. Secondary safety endpoints: 15. Physical examination and vital signs at Week 6.1 and Week 12; 16. Time to amputation of target leg until Month 12.;Timepoint(s) of evaluation of this end point: 1. Weeks 2, 4, 6, 8, 12, w/o LOCF; 2. Weeks 2, 4, 6, 8, 12, w/o LOCF; 3. Weeks 2, 4, 6, 8, 12, w/o LOCF; 4. Weeks 2, 4, 6, 8, 12, w/o LOCF; 5. Days 1 and 2, Weeks 1, 2, 4, 6, 6.1, 6.2, 6.3, 8, 12; 6. A priori specification not possible; between baseline and week 12; 7. Weeks 2, 4, 6, 8, 12; 8. A priori specification not possible; between baseline and week 12; 9. Weeks 2, 4, 6, 8, 12; 10. Day 0 and Week 6.1 prior IMP-application, Weeks 1, 2, 4, 6, 8, 12; 11. A priori specification not possible; between baseline and month 12; 12. Both Screening Visits, Days 0, 1, 2 and Weeks 1, 2, 4, 6, 6.1, 6.2, 6.3, 8, 12; 13. Screening V1, V3, Weeks 4 and 12; 14. Screening V1, V3, Weeks 4 and 12. 15. Weeks 6.1 and 12; 16. A priori specification not possible; between baseline and month 12. | — |
Countries
Germany
Contacts
Public ContactInformation Office
RHEACELL GmbH & Co. KG
Outcome results
None listed