Allogeneic ABCB5-positive Dermal Mesenchymal Stromal Cells for Treatment of CVU (Phase IIb)

NCT ID: NCT04971161

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-18
• Study Completion Date: 2025-11-25

Brief Summary

The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction of CVUs) and safety (by monitoring adverse events [AEs]) of three dose groups of the investigational medicinal product (IMP) allo-APZ2-CVU, topically administered on target wounds of patients with CVU compared to placebo.

Detailed Description

This is a randomized, placebo-controlled, double-blind, dose-ranging, multicenter, phase IIb clinical trial to investigate the efficacy and safety of the IMP allo-APZ2-CVU on wound healing in patients with therapy-resistant CVU. The allogeneic IMP allo-APZ2-CVU contains skin-derived ABCB5-positive dermal mesenchymal stromal cells isolated from skin tissue of healthy donors and stored in a donor cell bank.

Patients will be randomized to be treated with allo-APZ2-CVU (dose 1, dose 2, dose 3) or placebo (50 patients per dose group). The patients will undergo treatment with the IMP on Day 0 (V3) and will be followed up for efficacy for 18 weeks (V4 until V14). Two safety follow-up visits will be performed at Month 6 (V15) and Month 10 (V16). An additional visit (V17) will be performed to follow up on target wounds of all patients who reached the primary endpoint (i.e. wound was closed at V13 and V14) at Month 16 (at least).

The wound healing process will be documented by standardized photography. The wound size measurement will start at the first Screening Visit (V1) and will be measured at each following on-site visit.

Pain will be assessed using a numerical rating scale and quality of life will be investigated with standardized and validated questionnaires.

Conditions

Skin Ulcer Venous Stasis Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

allo-APZ2-CVU (dose group 1: 1 x 10e6 cells/cm²)

Application of IMP on patients wound

Group Type: EXPERIMENTAL

allo-APZ2-CVU

Intervention Type: BIOLOGICAL

Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.

Placebo

Application of IMP on patients wound

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One topical application with a syringe

allo-APZ2-CVU (dose group 2: 3 x 10e6 cells/cm²)

Application of IMP on patients wound

Group Type: EXPERIMENTAL

allo-APZ2-CVU

Intervention Type: BIOLOGICAL

Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.

allo-APZ2-CVU (dose group 3: 6 x 10e6 cells/cm²)

Application of IMP on patients wound

Group Type: EXPERIMENTAL

allo-APZ2-CVU

Intervention Type: BIOLOGICAL

Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.

Interventions

allo-APZ2-CVU

Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.

Intervention Type: BIOLOGICAL

Placebo

One topical application with a syringe

Intervention Type: DRUG

Other Intervention Names

Skin-derived ABCB5-positive dermal mesenchymal stromal cells

Eligibility Criteria

Inclusion Criteria

1. Male or female patients at least 18 years old;

2. 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;

3. Wound size of target ulcer between 1 and 50 cm² measured by a standardized photography at the screening visit;

4. 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);

5. Body mass index between 15 and 50 kg/m²;

6. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;

7. Women of childbearing potential must have a negative blood pregnancy test at Visit 1;

8. 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

1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone;

2. Diabetes mellitus that has to be confirmed by blood test (Hemoglobin A1c >7.5%);

3. Peripheral Artery Disease including claudication with need of treatment;

4. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;

5. Unable to tolerate leg ulcer compression bandage;

6. Infection of the target ulcer requiring treatment as judged clinically;

7. All diagnosed disorders, unrelated to CVU, that are influencing wound healing of the target wound at investigator's discretion;

8. Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);

9. 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;

10. 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;

11. Pregnant or lactating women;

12. Any known allergies to components of the IMP;

13. Prior surgical procedures such as bypass or mesh-graft treatment at target leg within 2 months prior to Visit 1 at target leg;

14. Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1;

15. Treatment of target ulcer with active wound care agents (e.g. Iruxol®N), which have not been paused 14 days before IMP application;

16. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;

17. Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion);

18. Employees of the sponsor, or employees or relatives of the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FGK Clinical Research GmbH

INDUSTRY

Sponsor Role: collaborator

RHEACELL GmbH & Co. KG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas Kerstan, Dr.

Role: PRINCIPAL_INVESTIGATOR

Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg

Locations

MVZ Gefäßzentrum Aachen am Marienhospital Aachen GmbH

Aachen, , Germany

Universitätsklinikum Augsburg, Klinik für Dermatologie und Allergologie, Campus Süd

Augsburg, , Germany

Fachklinik Bad Bentheim, Dermatologische Ambulanz

Bad Bentheim, , Germany

Helios Klinikum Berlin-Buch, Klinik für Plastische und Ästhetische Chirurgie

Berlin, , Germany

Helios Klinikum Emil von Behring, Klinik für Plastische und Ästhetische Chirurgie

Berlin, , Germany

Hautarztpraxis Dr. Niesmann & Dr. Othlinghaus, Hautzentrum im Jahrhunderthaus

Bochum, , Germany

Katholisches Klinikum Bochum gGmbH, Venenzentrum der Kliniken für Dermatologie und Gefäßchirurgie der Ruhr-Universität Bochum

Bochum, , Germany

Hautärzte Braunschweig am Altstadtmarkt, Hautärztliche Gemeinschaftspraxis

Braunschweig, , Germany

Klinikum Bremerhaven Reinkenheide gGmbH, Klinik für Dermatologie, Allergologie und Phlebologie, Wundzentrum

Bremerhaven, , Germany

Klinische Forschung Dresden GmbH

Dresden, , Germany

Universitätsklinikum Erlangen, Hautklinik - Wundzentrum Dermatologie

Erlangen, , Germany

Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie

Essen, , Germany

Universitätsklinikum Freiburg, Klinik für Dermatologie und Venerologie

Freiburg im Breisgau, , Germany

Marienhospital Gelsenkirchen GmbH, Klinik für Chirurgie (Allgemein-, Viszeral- und Endokrine Chirurgie, Thorax-, Gefäß- und Endovaskuläre Chirurgie und Kinderchirurgie)

Gelsenkirchen, , Germany

SRH Wald-Klinikum Gera GmbH, Zentrum für Klinische Studien

Gera, , Germany

Universitätsmedizin Greifswald, Klinik und Poliklinik für Hautkrankheiten

Greifswald, , Germany

Praxis Dr. med. Abdou Zarzour

Halle, , Germany

Universitätsklinikum Hamburg- Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP)

Hamburg, , Germany

MVZ Prof. Dr. Ockenfels, Haut und Allergie-Praxisklinik GmbH

Hanau, , Germany

Klinikum Region Hannover GmbH, KRH Klinikum Siloah, Klinik für Nephrologie, Angiologie und Rheumatologie

Hanover, , Germany

Zentrum für Dermatochirurgie, St. Josefskrankenhaus Heidelberg GmbH

Heidelberg, , Germany

SRH Klinikum Karlsbad- Langensteinbach GmbH, Interdisziplinäres Gefäßzentrum Innere Medizin

Karlsbad, , Germany

Medizinisches Versorgungszentrum DermaKiel GmbH

Kiel, , Germany

Hautarztpraxis Langenau, Studienzentrum

Langenau, , Germany

Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie

Leipzig, , Germany

Diabetologikum Ludwigshafen, die Praxis am Ludwigsplatz

Ludwigshafen, , Germany

Beldio Research GmbH

Memmingen, , Germany

Klinikum der Ludwig-Maximilians-Universität München, Klinik und Poliklinik für Dermatologie und Allergologie

München, , Germany

Universitätsklinikum Münster, Klinik für Hautkrankheiten, Allgemeine Dermatologie und Venerologie

Münster, , Germany

Klinikum Nürnberg Nord, Klinik für Dermatologie

Nuremberg, , Germany

MVZ Corius Potsdam GmbH, Dermatologie Potsdam MVZ

Potsdam, , Germany

Caritas-Krankenhaus St. Josef, Klinik für Plastische und Ästhetische, Hand- und Wiederherstellungschirurgie

Regensburg, , Germany

Universitätsmedizin Rostock, Klinik und Poliklinik für Dermatologie und Venerologie

Rostock, , Germany

Helios Kliniken Schwerin, Plastische, Rekonstruktive und Ästhetische Chirurgie

Schwerin, , Germany

Hautärztliche Gemeinschaftspraxis Dr. Leitz und Kollegen

Stuttgart, , Germany

Universitätsklinikum Tübingen, Universitäts-Hautklinik Tübingen

Tübingen, , Germany

Helios Universitätsklinikum Wuppertal, Zentrums für Dermatologie, Allergologie und Dermatochirurgie

Wuppertal, , Germany

Universitätsklinikum Würzburg, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie

Würzburg, , Germany

Countries

Germany

Other Identifiers

allo-APZ2-CVU-IIb

Identifier Type: -

Identifier Source: org_study_id

2023-510162-27-00

Identifier Type: CTIS

Identifier Source: secondary_id

U1111-1301-6596

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-004960-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id