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

Phase 2

Recruiting

• Conditions: Skin Ulcer Venous Stasis Chronic
• Interventions: Drug: Placebo; Biological: allo-APZ2-CVU

• Registration Number: NCT04971161
• Lead Sponsor: RHEACELL GmbH & Co. KG

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.

Study Timeline

• Study First Submitted: 2021-06-07
• Study First Submitted QC: 2021-07-12
• Study First Posted: 2021-07-21
• Study Start: 2021-08-18
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-23
• Last Update Posted: 2024-08-26
• Primary Completion: 2026-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Application of IMP on patients wound
allo-APZ2-CVU (dose group 1: 1 x 10e6 cells/cm²)	allo-APZ2-CVU	Application of IMP on patients wound
allo-APZ2-CVU (dose group 3: 6 x 10e6 cells/cm²)	allo-APZ2-CVU	Application of IMP on patients wound
allo-APZ2-CVU (dose group 2: 3 x 10e6 cells/cm²)	allo-APZ2-CVU	Application of IMP on patients wound

Primary Outcome Measures

Name	Time	Method
Assessment of adverse event (AE) occurrence	Up to 10 months	All AEs occurring during the clinical trial will be registered, documented and evaluated.
Complete wound closure at Week 18 already persisting for at least two weeks	Week 18	Complete wound closure at Week 18 already persisting for at least two weeks will be evaluated.

Secondary Outcome Measures

Name	Time	Method
Wound size change in percent at each post-baseline follow-up visit	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10	Wound size change in percent at each post-baseline follow-up visit will be evaluated.
Time to complete wound closure	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10	Time to complete wound closure will be evaluated.
Duration of wound closure	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10	Duration of wound closure will be evaluated.
Quality of wound healing (granulation tissue together with epithelialization) at each post-baseline follow-up visit	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10	The Quality of wound healing will be assessed at each post-baseline follow-up visit on the basis of the formation of granulation tissue together with epithelialization.
Quality of wound healing (scar formation) at each post-baseline follow-up visit	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10	The Quality of wound healing will be assessed at each post-baseline follow-up visit on the basis of the questions regarding scar formation.
Physical examination and vital signs at V14	Week 18	A physical body examination (e.g. general appearance, thyroid, head, lungs and thorax, ears, cardiovascular system, eyes, abdomen, nose-mouth-throat, musculoskeletal system, skin, extremities, lymph nodes, neurological system) will be performed and abnormal physical examination results will be evaluated and reported as AEs.
Complete wound closures at each post-baseline follow-up visit	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10, Month 16	Complete wound closures at each post-baseline follow-up visit will be evaluated.
Recurrence of the wound	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10, Month 16	Recurrence of the wound will be evaluated.
Quality of wound healing (wound exudate) at each post-baseline follow-up visit	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10, Month 16	The Quality of wound healing will be assessed at each post-baseline follow-up visit on the basis of the amount and type of wound exudate.
Assessment of Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14, V15, V16	Week 6, 12, 18, Month 6 and 10	Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14, V15, V16 will be evaluated.
Pain assessment as per numerical rating scale on each post-baseline follow-up visit	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10	Pain assessment as per numerical rating scale on each post-baseline follow-up visit will be evaluated.

Trial Locations

Locations (38)

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, 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; 🇩🇪 Hannover, 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; 🇩🇪 Nürnberg, 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