Clinical trial NCT04971161: Allogeneic ABCB5-positive Dermal Mesenchymal Stromal Cells for Treatment of CVU (Phase IIb)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Skin Ulcer Venous Stasis Chronic
Keywords: Chronic Venous Ulcer
ABCB5
Allogeneic
Dermal mesenchymal stromal cells
varicose ulcer
skin ulcer
advanced therapy medicinal product
somatic cell therapy
phase IIb
Lead sponsor: RHEACELL GmbH & Co. KG
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
First posted: 2021-07-21
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled, double-blind, dose-ranging, interventional, multicenter, phase IIb clinical trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Complete wound closure at Week 18 already persisting for at least two weeks
timeFrame: Week 18
measure: Assessment of adverse event (AE) occurrence
timeFrame: Up to 10 months
Secondary outcomes:
measure: Wound size change in percent at each post-baseline follow-up visit
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
measure: Time to complete wound closure
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
measure: Complete wound closures at each post-baseline follow-up visit
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10, Month 16
measure: Duration of wound closure
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
measure: Recurrence of the wound
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10, Month 16
measure: Quality of wound healing (wound exudate) at each post-baseline follow-up visit
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10, Month 16
measure: Quality of wound healing (granulation tissue together with epithelialization) at each post-baseline follow-up visit
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
measure: Quality of wound healing (scar formation) at each post-baseline follow-up visit
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
measure: Assessment of Quality of Life using the Wound-Quality of Life Questionnaire at V8, V11, V14, V15, V16
timeFrame: Week 6, 12, 18, Month 6 and 10
measure: Pain assessment as per numerical rating scale on each post-baseline follow-up visit
timeFrame: Day 1-2, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, Month 6 and 10
measure: Physical examination and vital signs at V14
timeFrame: Week 18
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: MVZ Gefäßzentrum Aachen am Marienhospital Aachen GmbH
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg, Klinik für Dermatologie und Allergologie, Campus Süd
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim, Dermatologische Ambulanz
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch, Klinik für Plastische und Ästhetische Chirurgie
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring, Klinik für Plastische und Ästhetische Chirurgie
city: Bochum
country: Germany
facility: Hautarztpraxis Dr. Niesmann & Dr. Othlinghaus, Hautzentrum im Jahrhunderthaus
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum gGmbH, Venenzentrum der Kliniken für Dermatologie und Gefäßchirurgie der Ruhr-Universität Bochum
city: Braunschweig
country: Germany
facility: Hautärzte Braunschweig am Altstadtmarkt, Hautärztliche Gemeinschaftspraxis
city: Bremerhaven
country: Germany
facility: Klinikum Bremerhaven Reinkenheide gGmbH, Klinik für Dermatologie, Allergologie und Phlebologie, Wundzentrum
city: Dresden
country: Germany
facility: Klinische Forschung Dresden GmbH
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Hautklinik - Wundzentrum Dermatologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Dermatologie und Venerologie
city: Gelsenkirchen
country: Germany
facility: Marienhospital Gelsenkirchen GmbH, Klinik für Chirurgie (Allgemein-, Viszeral- und Endokrine Chirurgie, Thorax-, Gefäß- und Endovaskuläre Chirurgie und Kinderchirurgie)
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH, Zentrum für Klinische Studien
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Klinik und Poliklinik für Hautkrankheiten
city: Halle
country: Germany
facility: Praxis Dr. med. Abdou Zarzour
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg- Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP)
city: Hanau
country: Germany
facility: MVZ Prof. Dr. Ockenfels, Haut und Allergie-Praxisklinik GmbH
city: Hannover
country: Germany
facility: Klinikum Region Hannover GmbH, KRH Klinikum Siloah, Klinik für Nephrologie, Angiologie und Rheumatologie
city: Heidelberg
country: Germany
facility: Zentrum für Dermatochirurgie, St. Josefskrankenhaus Heidelberg GmbH
city: Karlsbad
country: Germany
facility: SRH Klinikum Karlsbad- Langensteinbach GmbH, Interdisziplinäres Gefäßzentrum Innere Medizin
city: Kiel
country: Germany
facility: Medizinisches Versorgungszentrum DermaKiel GmbH
city: Langenau
country: Germany
facility: Hautarztpraxis Langenau, Studienzentrum
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
city: Ludwigshafen
country: Germany
facility: Diabetologikum Ludwigshafen, die Praxis am Ludwigsplatz
city: Memmingen
country: Germany
facility: Beldio Research GmbH
city: München
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universität München, Klinik und Poliklinik für Dermatologie und Allergologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Hautkrankheiten, Allgemeine Dermatologie und Venerologie
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord, Klinik für Dermatologie
city: Potsdam
country: Germany
facility: MVZ Corius Potsdam GmbH, Dermatologie Potsdam MVZ
city: Regensburg
country: Germany
facility: Caritas-Krankenhaus St. Josef, Klinik für Plastische und Ästhetische, Hand- und Wiederherstellungschirurgie
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock, Klinik und Poliklinik für Dermatologie und Venerologie
city: Schwerin
country: Germany
facility: Helios Kliniken Schwerin, Plastische, Rekonstruktive und Ästhetische Chirurgie
city: Stuttgart
country: Germany
facility: Hautärztliche Gemeinschaftspraxis Dr. Leitz und Kollegen
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Universitäts-Hautklinik Tübingen
city: Wuppertal
country: Germany
facility: Helios Universitätsklinikum Wuppertal, Zentrums für Dermatologie, Allergologie und Dermatochirurgie
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Study officials:
affiliation: Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg
name: Andreas Kerstan, Dr.
role: PRINCIPAL_INVESTIGATOR
References: