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

A Randomized, Placebo-Controlled, Double-blind, Dose-Ranging, Multicenter, Phase IIb Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-CVU on Wound Healing of Therapy-Resistant Chronic Venous Ulcer (CVU)

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.

Study Overview

• Status: Recruiting
• Conditions: Skin Ulcer Venous Stasis Chronic
• Intervention / Treatment: Biological: allo-APZ2-CVU; Drug: 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).

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 Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christoph Ganss, Dr.; Phone Number: +49 6221 71833; Email: office@rheacell.com
• Study Contact Backup: Name: Anna Mößmer; Phone Number: +49 6221 71833; Email: anna.moessmer@rheacell.com

Study Locations

• Germany
  • Aachen, Germany, 52066
    • Recruiting
    • MVZ Gefäßzentrum Aachen am Marienhospital Aachen GmbH
    • Contact: Jens D Puschmann
  • Augsburg, Germany, 86179
    • Recruiting
    • Universitätsklinikum Augsburg, Klinik für Dermatologie und Allergologie, Campus Süd
    • Contact: Julia Welzel, Prof. Dr.
  • Bad Bentheim, Germany, 48455
    • Recruiting
    • Fachklinik Bad Bentheim, Dermatologische Ambulanz
    • Contact: Athanasios Tsianakas, PD Dr. med.
  • Berlin, Germany, 13125
    • Recruiting
    • Helios Klinikum Berlin-Buch, Klinik für Plastische und Ästhetische Chirurgie
    • Contact: Oliver C. Thamm, PD Dr. med.
  • Berlin, Germany, 14165
    • Recruiting
    • Helios Klinikum Emil von Behring, Klinik für Plastische und Ästhetische Chirurgie
    • Contact: Daniel Schiltz, Dr. med.
  • Berlin, Germany, 10787
    • Withdrawn
    • Franziskus-Krankenhaus Berlin, Klinik für Innere Medizin, Angiologie und Diabetologie
  • Bochum, Germany, 44793
    • Recruiting
    • Hautarztpraxis Dr. Niesmann & Dr. Othlinghaus, Hautzentrum im Jahrhunderthaus
    • Contact: Johannes Niesmann, Dr. med.
  • Bochum, Germany, 44805
    • Recruiting
    • Katholisches Klinikum Bochum gGmbH, Venenzentrum der Kliniken für Dermatologie und Gefäßchirurgie der Ruhr-Universität Bochum
    • Contact: Markus Stücker, Prof. Dr.
  • Braunschweig, Germany, 38100
    • Recruiting
    • Hautärzte Braunschweig am Altstadtmarkt, Hautärztliche Gemeinschaftspraxis
    • Contact: Herms Wittstock, Dr. med.
  • Bremerhaven, Germany, 27574
    • Recruiting
    • Klinikum Bremerhaven Reinkenheide gGmbH, Klinik für Dermatologie, Allergologie und Phlebologie, Wundzentrum
    • Contact: Michael M. Sachse, Dr. med.
  • Dresden, Germany, 01069
    • Recruiting
    • Klinische Forschung Dresden GmbH
    • Contact: Peter Heymer, Dr. med.
  • Dresden, Germany, 01307
    • Withdrawn
    • Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden, Medizinische Klinik und Poliklinik III Angiologie und Gefäßzentrum
  • Düsseldorf, Germany, 40225
    • Withdrawn
    • Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Klinik für Dermatologie
  • Erlangen, Germany, 91054
    • Recruiting
    • Universitätsklinikum Erlangen, Hautklinik - Wundzentrum Dermatologie
    • Contact: Cornelia Erfurt-Berge, PD Dr. med.
  • Essen, Germany, 45147
    • Recruiting
    • Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
    • Contact: Joachim Dissemond, Prof. Dr.
  • Freiburg, Germany, 79104
    • Terminated
    • Universitätsklinikum Freiburg, Klinik für Dermatologie und Venerologie
  • Gelsenkirchen, Germany, 45886
    • Recruiting
    • Marienhospital Gelsenkirchen GmbH, Klinik für Chirurgie (Allgemein-, Viszeral- und Endokrine Chirurgie, Thorax-, Gefäß- und Endovaskuläre Chirurgie und Kinderchirurgie)
    • Contact: Mansur Duran, PD Dr. med.
  • Gera, Germany, 07548
    • Recruiting
    • SRH Wald-Klinikum Gera GmbH, Zentrum für Klinische Studien
    • Contact: Sabine Sell
  • Greifswald, Germany, 17475
    • Recruiting
    • Universitätsmedizin Greifswald, Klinik und Poliklinik für Hautkrankheiten
    • Contact: Stine Lutze, Dr. med.
  • Halle, Germany, 06108
    • Recruiting
    • Praxis Dr. med. Abdou Zarzour
    • Contact: Abdou Zarzour, Dr. med.
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitätsklinikum Hamburg- Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP)
    • Contact: Matthias Augustin, Prof. Dr.
  • Hanau, Germany, 63450
    • Recruiting
    • MVZ Prof. Dr. Ockenfels, Haut und Allergie-Praxisklinik GmbH
    • Contact: Hans Michael Ockenfels, Prof. Dr.
  • Hannover, Germany, 30459
    • Recruiting
    • Klinikum Region Hannover GmbH, KRH Klinikum Siloah, Klinik für Nephrologie, Angiologie und Rheumatologie
    • Contact: Jan Menne, Prof. Dr.
  • Heidelberg, Germany, 69115
    • Recruiting
    • Zentrum für Dermatochirurgie, St. Josefskrankenhaus Heidelberg GmbH
    • Contact: Moritz Felcht, Prof. Dr.
  • Karlsbad, Germany, 76307
    • Recruiting
    • SRH Klinikum Karlsbad- Langensteinbach GmbH, Interdisziplinäres Gefäßzentrum Innere Medizin
    • Contact: Rüdiger von Bauer, Dr. med.
  • Kiel, Germany, 24148
    • Terminated
    • Medizinisches Versorgungszentrum DermaKiel GmbH
  • Krefeld, Germany, 47805
    • Withdrawn
    • Helios Klinikum Krefeld, Klinik für Dermatologie und Venerologie
  • Langenau, Germany, 89129
    • Recruiting
    • Hautarztpraxis Langenau, Studienzentrum
    • Contact: Beate Schwarz, Dr. med.
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
    • Contact: Jan C. Simon, Prof. Dr.
  • Leipzig, Germany, 04315
    • Withdrawn
    • Studienambulanz Dr. Schubert Leipzig
  • Ludwigshafen, Germany, 67059
    • Recruiting
    • Diabetologikum Ludwigshafen, die Praxis am Ludwigsplatz
    • Contact: Lutz Stemler, Dr. med.
  • Memmingen, Germany, 87700
    • Recruiting
    • Beldio Research GmbH
    • Contact: Andreas Schwinn, Dr. med.
  • München, Germany, 80337
    • Recruiting
    • Klinikum der Ludwig-Maximilians-Universität München, Klinik und Poliklinik für Dermatologie und Allergologie
    • Contact: Daniela Hartmann, PD Dr. med.
  • München, Germany, 80636
    • Withdrawn
    • Dermazentrum München, Standort Neuhausen, Studienzentrum
  • Münster, Germany, 48149
    • Recruiting
    • Universitätsklinikum Münster, Klinik für Hautkrankheiten, Allgemeine Dermatologie und Venerologie
    • Contact: Tobias Görge, Prof. Dr.
  • Nürnberg, Germany, 90419
    • Recruiting
    • Klinikum Nürnberg Nord, Klinik für Dermatologie
    • Contact: Erwin S. Schultz, Prof. Dr.
  • Potsdam, Germany, 14467
    • Recruiting
    • MVZ Corius Potsdam GmbH, Dermatologie Potsdam MVZ
    • Contact: Khusru Asadullah, Prof. Dr.
  • Regensburg, Germany, 93053
    • Recruiting
    • Caritas-Krankenhaus St. Josef, Klinik für Plastische und Ästhetische, Hand- und Wiederherstellungschirurgie
    • Contact: Stephan Seitz, PD Dr. med.
  • Rostock, Germany, 18057
    • Recruiting
    • Universitätsmedizin Rostock, Klinik und Poliklinik für Dermatologie und Venerologie
    • Contact: Susen Rode
  • Schwerin, Germany, 19049
    • Recruiting
    • Helios Kliniken Schwerin, Plastische, Rekonstruktive und Ästhetische Chirurgie
    • Contact: Frank Masberg, Dr. med.
  • Stuttgart, Germany, 70178
    • Recruiting
    • Hautärztliche Gemeinschaftspraxis Dr. Leitz und Kollegen
    • Contact: Nicolas Leitz, Dr. med.
  • Tübingen, Germany, 72076
    • Recruiting
    • Universitätsklinikum Tübingen, Universitäts-Hautklinik Tübingen
    • Contact: Anke Strölin, Prof. Dr.
  • Wuppertal, Germany, 42283
    • Recruiting
    • Helios Universitätsklinikum Wuppertal, Zentrums für Dermatologie, Allergologie und Dermatochirurgie
    • Contact: Silke C. Hofmann, Prof. Dr.
  • Würzburg, Germany, 97080
    • Recruiting
    • Universitätsklinikum Würzburg, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
    • Contact: Andreas Kerstan, PD Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: allo-APZ2-CVU (dose group 1: 1 x 10e6 cells/cm²); Application of IMP on patients wound	Biological: allo-APZ2-CVU; Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.; Other Names: Skin-derived ABCB5-positive dermal mesenchymal stromal cells
Placebo Comparator: Placebo; Application of IMP on patients wound	Drug: Placebo; One topical application with a syringe
Experimental: allo-APZ2-CVU (dose group 2: 3 x 10e6 cells/cm²); Application of IMP on patients wound	Biological: allo-APZ2-CVU; Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.; Other Names: Skin-derived ABCB5-positive dermal mesenchymal stromal cells
Experimental: allo-APZ2-CVU (dose group 3: 6 x 10e6 cells/cm²); Application of IMP on patients wound	Biological: allo-APZ2-CVU; Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.; Other Names: Skin-derived ABCB5-positive dermal mesenchymal stromal cells

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound size change in percent at each post-baseline follow-up visit	Wound size change in percent at each post-baseline follow-up visit will be evaluated.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Time to complete wound closure	Time to complete wound closure will be evaluated.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Complete wound closures at each post-baseline follow-up visit	Complete wound closures at each post-baseline follow-up visit will be evaluated.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Duration of wound closure	Duration of wound closure will be evaluated.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Recurrence of the wound	Recurrence of the wound will be evaluated.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Quality of wound healing (wound exudate) at each post-baseline follow-up visit	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.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Quality of wound healing (granulation tissue together with epithelialization) at each post-baseline follow-up visit	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.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Quality of wound healing (scar formation) at each post-baseline follow-up visit	The Quality of wound healing will be assessed at each post-baseline follow-up visit on the basis of the questions regarding scar formation.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Assessment of Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14	Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14 will be evaluated.	Week 6, 12, 18
Pain assessment as per numerical rating scale on each post-baseline efficacy follow-up visit	Pain assessment as per numerical rating scale on each post-baseline efficacy follow-up visit will be evaluated.	Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
Physical examination and vital signs at V14	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.	Week 18

Collaborators and Investigators

• Sponsor: RHEACELL GmbH & Co. KG
• Collaborators: FGK Clinical Research GmbH
• Investigators: Principal Investigator: Andreas Kerstan, Dr., Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Allogeneic; varicose ulcer; Chronic Venous Ulcer; ABCB5; skin ulcer; advanced therapy medicinal product; somatic cell therapy; Dermal mesenchymal stromal cells; phase IIb
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Leg Ulcer; Varicose Veins; Ulcer; Varicose Ulcer; Skin Ulcer
• Other Study ID Numbers: allo-APZ2-CVU-IIb

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No