Allogeneic ABCB5-positive Dermal Mesenchymal Stromal Cells for Treatment of Therapy-resistant CVU (Phase III)

A Pivotal, Randomized, Placebo-controlled, Double-blind, Multicenter, International Phase III Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-CVU on Wound Healing of Therapy-Resistant Non-Healing Chronic Venous Ulcers (CVU)

The aim of this clinical trial is to investigate the efficacy and safety of allo-APZ2-CVU, administered topically on therapy-resistant non-healing CVUs compared to placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Venous Leg Ulcer
• Intervention / Treatment: Drug: Placebo; Drug: allo-APZ2-CVU

Detailed Description

This is a pivotal, randomized, placebo-controlled, double-blind, multicenter, international phase III clinical trial to investigate the efficacy and safety of the IMP allo-APZ2-CVU on wound healing in patients with therapy-resistant non-healing 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 or placebo. 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). Three safety follow-up visits will be performed at Month 6 (V15), Month 10 (V16) and Month 16 (V17).

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): 250
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Multiple Locations, Austria
    • RHEACELL Clinical Trial Site
• Czechia
  • Multiple Locations, Czechia
    • RHEACELL Clinical Trial Site
• France
  • Multiple Locations, France
    • RHEACELL Clinical Trial Site
• Germany
  • Several Locations, Germany
    • RHEACELL Clinical Trial Site
• Hungary
  • Multiple Locations, Hungary
    • RHEACELL Clinical Trial Site
• Italy
  • Multiple Locations, Italy
    • RHEACELL Clinical Trial Site
• Netherlands
  • Multiple Locations, Netherlands
    • RHEACELL Clinical Trial Site
• Poland
  • Multiple Locations, Poland
    • RHEACELL Clinical Trial Site
• Slovakia
  • Multiple Locations, Slovakia
    • RHEACELL Clinical Trial Site
• Sweden
  • Multiple Locations, Sweden
    • RHEACELL Clinical Trial Site
• United Kingdom
  • Multiple Locations, United Kingdom
    • RHEACELL Clinical Trial Site
• United States
  • Florida
    • Hialeah, Florida, United States, 33012
      • RHEACELL Clinical Trial Site
    • Miami, Florida, United States, 33136
      • RHEACELL Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • RHEACELL Clinical Trial Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • RHEACELL Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients at least 18 years old;
2. Chronic venous leg ulcer at lower leg and/or ankle region that has not been present longer than 15 years, diagnosed by Doppler or Duplex sonography, ankle brachial index, physical examination and dermatological review;
3. Wound size at V1 and V2 between 1 and 25 cm˄2 as measured by standardized photography;
4. If patients have 2 or more ulcers at the same extremity, the target ulcer has to be separated from the other ulcers with a bridge of epithelialized skin at least 1 cm wide;
5. Body mass index between 15 and 50 kg/m²;
6. Patients able to understand the nature of the study and able to provide written informed consent prior to any clinical trial procedures;
7. Women of childbearing potential must have a negative urine pregnancy test at Visit 1;
8. During the course of the clinical trial women of childbearing potential and their male partners must be willing to use highly effective contraceptive methods as defined in the EMA CTCG "Recommendations related to contraception and pregnancy testing in clinical trials" Version 1.2.

Exclusion Criteria:

1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
2. Uncontrolled Diabetes mellitus i.e. Hemoglobin A1c (HbA1c) >9.0% (75 mmol/mol) (measured by blood test);
3. Peripheral Artery Disease including claudication with need of treatment or intervention;
4. Acute deep vein thrombosis diagnosed within 30 days before V1, or untreated deep vein thrombosis;
5. Wounds showing size reduction of more than 40% at Visit 2 compared to Visit 1;
6. Patients with known hypersensitivity and/or clinical contraindications to the compression systems used in the clinical trial, or inability/unwillingness to tolerate leg ulcer compression systems;
7. Acute wound infection of ulcer requiring treatment as judged clinically;
8. Current use of medications that are known to influence wound healing i.e. systemic immunosuppressives, cytotoxic medicinal products, systemic steroids (above Cushingthreshold level) at investigator´s discretion;
9. Patients 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 an 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. Known hypersensitivities to the active substance or to any of the excipients in the IP or the placebo;
13. Surgical procedure affecting the CVU, such as bypass or mesh graft performed within two months prior to Visit 1;
14. Current or previous (within 30 days of enrollment) treatment with another IP, or participation in another clinical trial, including follow-up phase;
15. Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion);
16. Employees of the sponsor, or employees or relatives of the investigator(s).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: Verum	Drug: allo-APZ2-CVU; Allogeneic dermal ABCB5-positive Mesenchymal Stromal Cells (ABCB5+ MSCs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete wound closure	Complete wound closure already persisting for at least two weeks	18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete wound closures at each post-baseline follow-up visit	Complete wound closures at each post-baseline follow-up visit	at each post-baseline follow-up visit (starting the day after intervention until month 16)

Collaborators and Investigators

• Sponsor: RHEACELL GmbH & Co. KG
• Collaborators: FGK Clinical Research GmbH
• Investigators: Study Director: Anna Moessmer, RHEACELL GmbH & Co. KG

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Allogeneic; phase III; varicose ulcer; Chronic Venous Ulcer; ABCB5; skin ulcer; advanced therapy medicinal product; somatic cell therapy; Dermal mesenchymal stromal cells
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Skin Diseases; Varicose Veins; Leg Ulcer; Skin and Connective Tissue Diseases; Varicose Ulcer; Skin Ulcer
• Other Study ID Numbers: allo-APZ2-CVU-III; 2024-512720-11-00 (Ctis); U1111-1305-5114 (Registry Identifier: World Health Organization [WHO] Registry Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No