Efficacy and Safety Evaluation of Allogeneic Skin-Derived ABCB5-Positive Dermal Mesenchymal Stromal Cells in Therapy-Resistant Chronic Venous Ulcers
- Trial ID
- 2023-510162-27-00
- Protocol
- allo-APZ2-CVU-IIb
- Sponsor
- Rheacell GmbH & Co. KG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **efficacy** and **safety** of three doses of the investigational medicinal product allo-APZ2-CVU, a cutaneous suspension containing allogeneic skin-derived ABCB5-positive dermal mesenchymal stromal cells, in patients with therapy-resistant **chronic venous ulcers** (CVU). Efficacy will be assessed by monitoring the wound closure of CVUs, while safety will be evaluated by monitoring adverse events. This study is clinically relevant as it aims to provide a potential therapeutic option for patients with CVUs that are resistant to conventional treatments, addressing a significant unmet medical need.
Participants
The clinical trial focuses on **chronic venous ulcers (CVU)**, with the objective of assessing the efficacy and safety of the investigational medicinal product allo-APZ2-CVU. The study population includes both male and female participants, aged 18 years and older, who are diagnosed with chronic venous leg ulcers as per current guidelines. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants are required to have a body mass index between 15 and 50 kg/m² and must provide written informed consent. Women of childbearing potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods during the trial. The trial population includes individuals with a wound size of the target ulcer between 1 and 50 cm², and if multiple ulcers are present, the target ulcer must be separated by at least 1 cm of epithelialized skin. The study involves a vulnerable population, and the selection criteria ensure that participants understand the nature of the procedure.
Plans and Procedures
The clinical trial is designed as a **randomized**, **placebo-controlled**, **double-blind**, dose-ranging, multicenter, Phase IIb study. The primary objective is to evaluate the efficacy and safety of the investigational medicinal product (IMP), allo-APZ2-CVU, in the treatment of therapy-resistant **chronic venous ulcers** (CVU). The trial will compare three different doses of the IMP, administered as a **cutaneous suspension**, against a placebo. The study is expected to run from June 2021 to June 2026, with the primary endpoint being complete wound closure at Week 18, persisting for at least two weeks, and monitoring of adverse events.
Participants will be involved in the study for a period that includes multiple visits. The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, wound characteristics, and health status. Follow-up visits will occur post-baseline to assess wound size changes, time to complete wound closure, and other secondary endpoints such as quality of life and pain assessment. The end-of-study visit will conclude the participant's involvement, evaluating the overall treatment outcomes and any long-term effects.
The expected length of participant involvement is approximately 18 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. Participants must meet specific inclusion criteria, such as being at least 18 years old, having a chronic venous leg ulcer as defined by current guidelines, and providing informed consent. Exclusion criteria are not specified in the provided data. The trial aims to provide valuable insights into the potential of allo-APZ2-CVU as a treatment for CVU, with a focus on both efficacy and safety.
Treatment
The clinical trial involves the use of **allo-APZ2-CVU_1**, a **cutaneous suspension** containing **allogeneic skin-derived ABCB5-positive dermal mesenchymal stromal cells**. This investigational medicinal product is administered topically on the target wounds of patients with therapy-resistant chronic venous ulcers (CVU). The dosage for **allo-APZ2-CVU_1** is set at a maximum of 1 million organisms per day, with a total treatment period of one day. The product is of biological origin and is developed by RHEACELL GMBH & CO. KG. The administration route is cutaneous use, ensuring direct application to the affected area.
Another formulation, **allo-APZ2-CVU_2**, also a **cutaneous suspension**, contains the same active substance, **allogeneic skin-derived ABCB5-positive dermal mesenchymal stromal cells**. This variant is administered at a higher dosage, with a maximum of 3 million organisms per day, maintaining the same one-day treatment period. The administration method remains cutaneous, and the product is similarly of biological origin, developed by the same manufacturer.
The third formulation, **allo-APZ2-CVU_3**, is identical in pharmaceutical form and active substance to the previous formulations. It is administered at the highest dosage of 6 million organisms per day, with the treatment period also limited to one day. The cutaneous route of administration is employed, and the product is of biological origin, produced by RHEACELL GMBH & CO. KG.
A **placebo** is used as a comparator in this trial. The placebo is designed to mimic the investigational product in appearance and administration method but does not contain the active substance. The placebo serves to provide a control for evaluating the efficacy and safety of the investigational products. The administration schedule and compliance monitoring for the placebo group are consistent with those of the active treatment groups to ensure the integrity of the trial results.
Efficacy
The efficacy of the investigational medicinal product (IMP) allo-APZ2-CVU in the treatment of therapy-resistant **Chronic Venous Ulcer (CVU)** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the complete wound closure at Week 18, which must persist for at least two weeks. This will be evaluated alongside the monitoring of adverse events to ensure safety. Secondary endpoints include the percentage change in wound size at each post-baseline follow-up visit, the time to complete wound closure, and the number of complete wound closures at each follow-up visit. Additional secondary measures involve the duration of wound closure, recurrence of the wound, and the quality of wound healing assessed at each follow-up visit.
Quality of life will be evaluated using the Wound-Quality of Life Questionnaire at specific visits (V8, V11, V14), and pain will be assessed using a numerical rating scale during each post-baseline efficacy follow-up visit. Physical examination and vital signs will be recorded at V14. These assessments will be conducted at various timepoints throughout the trial to provide a comprehensive evaluation of the IMP's efficacy in promoting wound healing in patients with CVU.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patients at least 18 years old;
- Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy-resistant ulcer that shows no tendency to heal within 3 months despite of optimal phlebological therapies or has not fully healed within 12 months) at lower leg and/or ankle region and has not been present longer than 15 years, diagnosed by doppler or duplex sonography, ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review;
- Wound size of target ulcer between 1 and 50 cm2 measured by a standardized photography at the screening visit;
- If patients have 2 or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of epithelialized skin from other ulcers (the largest ulcer should be the target ulcer, if not decided otherwise at discretion of the investigator; the target ulcer is defined at Visit 1);
- Body mass index between 15 and 50 kg/m²
- Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
- Women of childbearing potential must have a negative blood pregnancy test at Visit 1;
- 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
- Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
- Diabetes mellitus that has to be confirmed by blood test (Hemoglobin A1c >7.5%);
- Peripheral Artery Disease including claudication with need of treatment;
- Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
- Unable to tolerate leg ulcer compression bandage;
- Infection of the target ulcer requiring treatment as judged clinically;
- All diagnosed disorders, unrelated to CVU, that are influencing wound healing of the target wound at investigator’s discretion;
- Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
- Patient who, in the opinion of the investigator, for any reason are unable or unwilling to complete the trial per protocol (e.g. alcohol or substance abuse, not mobile, short life expectancy) or there is evidence of any other medical condition (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;
- 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;
- Pregnant or lactating women;
- Any known allergies to components of the IMP;
- Prior surgical procedures such as bypass or mesh-graft treatment at target leg within 2 months prior to Visit 1 at target leg;
- Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1;
- Treatment of target ulcer with active wound care agents (e.g. Iruxol®N), which have not been paused 14 days before IMP application;
- Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
- Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion);
- Employees of the sponsor, or employees or relatives of the investigator.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Jun 2021 | 200 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
allo-APZ2-CVU_2 | Test | CUTANEOUS SUSPENSION | CUTANEOUS USE | 3 | 1 | PRD8930697 |
allo-APZ2-CVU_1 | Test | CUTANEOUS SUSPENSION | CUTANEOUS USE | 1 | 1 | PRD5244687 |
allo-APZ2-CVU_3 | Test | CUTANEOUS SUSPENSION | CUTANEOUS USE | 6 | 1 | PRD8930698 |
Placebo | Placebo | N/A | — | — | — | N/A |