Skin Ulcer Venous Stasis Chronic
Conditions
Keywords
somatic cell therapy, phase I/IIa, mesenchymal stem cells, ABCB5+, APZ2, chronic venous ulcer, varicose ulcer, skin ulcer, advanced therapy medicinal product, APZ2-II-01, autologous use
Brief summary
The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction) and safety (by monitoring occurring adverse events) of the investigational medicinal product APZ2 after one single application on chronic venous leg ulcer wounds.
Detailed description
This is an interventional, single arm, phase I/IIa clinical trial to investigate the efficacy and safety of ABCB5+ mesenchymal stem cells (MSCs) on wound healing in patients with chronic venous ulcer (CVU). Autologous MSCs will be isolated ex vivo from a small skin biopsy and will be expanded in vitro. The IMP APZ2 containing the ABCB5+ cells will then be applied on the wound surface of CVU under local anesthesia. Patients are followed up for efficacy for 3 months which allows to distinguish actual wound healing from transient wound coverage. The wound healing process will be documented by standardized photography. The wound size evaluation will start on the day of the first change of wound dressing. The quality of the wound healing process will be assessed on the basis of formation of granulation tissue, epithelialization and wound exudation. Pain will be assessed using a numerical rating scale and quality of life will be investigated with standardized and validated questionnaires. To assess long-term safety of APZ2 an additional follow-up visit at Month 12 post IMP application is included.
Interventions
BIOLOGICALAPZ2 application
Application of IMP on patients wound.
Sponsors
Ticeba GmbH
FGK Clinical Research GmbH
Granzer Regulatory Consulting & Services
RHEACELL GmbH & Co. KG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 18 to 85 years; 2. Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy resistant ulcer that shows no improvement within 3 months despite of optimal phlebological therapies or is not healed within 12 months) for at least 6 weeks but shorter than 3 years diagnosed by doppler ultrasonography (DUS), ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review; 3. Wound size between 5 and 50 square cm measured by a standardized photography at the screening visit; 4. Wound location between knee and ankle; 5. Patients suffering from 2 ulcers at the same extremity, as long as these ulcers are separated by a minimum bridge of 1 cm of epithelialized skin; 6. Patients must agree to have at least one biopsy performed before treatment. In case IMP production from the first biopsy is not successful, a second biopsy will be taken; 7. Body mass index (BMI) between 20 and 40 kg/m²; 8. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure; 9. Women of childbearing potential must have a negative blood pregnancy test at Screening and at Visit 5 before the IMP application; 10. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of wound size reduction | Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing | Percentage of wound size reduction at Week 12, or last available post-baseline measurement if the Week 12 measurement is missing (last observation carried forward \[LOCF\]) |
| Assessment of adverse event (AE) occurrence | At biopsy removal, 1-3 days post biopsy, 7-10 days post biopsy, 6-12 weeks post biopsy; at baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 and month 12 post baseline | All during the clinical trial occurring AEs will be registered, documented and evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving complete wound closure | Weeks 2, 3, 4, 6, 8, 10, and 12 post baseline and at any time point up to week 12 | — |
| Time to first complete wound closure | Between baseline and week 12 post baseline | A priori specification not possible |
| Proportion of patients achieving 30% wound closure | Weeks 2, 3, 4, 6, 8, 10, 12 post baseline and at any time point up to week 12 | — |
| Time to first 30% wound closure | Between baseline and week 12 post baseline | A priori specification not possible |
| Percentage of wound epithelialization | At baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline | Amount of wound epithelialization in % of wound area will be assessed by the investigator based on image analysis of images taken from the wound. |
| Percentage of wound size reduction | Weeks 2, 3, 4, 6, 8, 10 and 12 post baseline | Percentage of wound size reduction at Weeks 2, 3, 4, 6, 8, 10 and 12 (without LOCF) |
| Pain assessment as per numerical rating scale (NRS) | At baseline and days 1-3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline | — |
| Quality of life (QoL) assessment using the SF-36 questionnaire | At baseline and weeks 4, 8, 12 post baseline | — |
| Dermatologic quality of life assessment using the DLQI questionnaire | At baseline and weeks 4, 8, 12 post baseline | — |
| Physical examination and vital parameters | At Screening, baseline, week 12, month 12 | — |
| Formation of granulation tissue and wound exudation | At baseline and days 3, 8 and weeks 2, 3, 4, 6, 8, 10, 12 post baseline | Formation of granulation tissue in % of wound area will be assessed by the investigator based on image analysis of images taken from the wound. Wound exudation will be classified by the investigator using following scores: * High: Small amounts of fluid or free fluids are visible when the dressing is removed; dressing is extensively marked or wet * Moderate: Small amounts of fluid are visible when dressing is removed; wound bed may appear glossy; Primary dressing may be lightly marked * Low: Wound bed is dry; there is no visible moisture; Primary dressing is unmarked; dressing may be adherent to wound |
| Absolute wound size reduction | Weeks 2, 3, 4, 6, 8, 10, and 12 post baseline | — |
Countries
Germany
Outcome results
None listed