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

Skin Ulcer Venous Stasis Chronic Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04971161
• Other study ID #: allo-APZ2-CVU-IIb
• Secondary ID: 2023-510162-27-0
• Status: Recruiting
• Phase: Phase 2
• Start date: August 18, 2021
• Est. completion date: June 2026

Study information

• Verified date: June 2024
• Source: RHEACELL GmbH & Co. KG
• Contact: Christoph Ganss, Dr.
• Phone: +49 6221 71833
• Email: office[@]rheacell.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Skin Ulcer
• Skin Ulcer Venous Stasis Chronic
• Ulcer
• Varicose Ulcer

Intervention

Biological:
• allo-APZ2-CVU
Suspension of ABCB5-positive dermal mesenchymal stromal cells. One topical application with a syringe.

Drug:
• Placebo
One topical application with a syringe

Locations

Country	Name	City	State
Germany	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	Franziskus-Krankenhaus Berlin, Klinik für Innere Medizin, Angiologie und Diabetologie	Berlin
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 "Carl Gustav Carus" der Technischen Universität Dresden, Medizinische Klinik und Poliklinik III Angiologie und Gefäßzentrum	Dresden
Germany	Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Klinik für Dermatologie	Düsseldorf
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	Helios Klinikum Krefeld, Klinik für Dermatologie und Venerologie	Krefeld
Germany	Hautarztpraxis Langenau, Studienzentrum	Langenau
Germany	Studienambulanz Dr. Schubert Leipzig	Leipzig
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	Dermazentrum München, Standort Neuhausen, Studienzentrum	München
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

Sponsors (2)

Lead Sponsor	Collaborator
RHEACELL GmbH & Co. KG	FGK Clinical Research GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Assessment of adverse event (AE) occurrence	All AEs occurring during the clinical trial will be registered, documented and evaluated.	Up to 10 months
Secondary	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
Secondary	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
Secondary	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, Month 16
Secondary	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
Secondary	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, Month 16
Secondary	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, Month 16
Secondary	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
Secondary	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
Secondary	Assessment of Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14, V15, V16	Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14, V15, V16 will be evaluated.	Week 6, 12, 18, Month 6 and 10
Secondary	Pain assessment as per numerical rating scale on each post-baseline follow-up visit	Pain assessment as per numerical rating scale on 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
Secondary	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