CLINICAL STUDY TO TEST STEM CELLS FOR THE TREATMENT OF LONG-TERM, NON-HEALING VENOUS LEG ULCERS

Phase 3

Recruiting

• Conditions: chronic venous ulcers (CVU)

• Registration Number: 2024-512720-11-00
• Lead Sponsor: Rheacell GmbH & Co. KG

Brief Summary

The aim of this clinical trial is to investigate the efficacy (by monitoring complete wound closure) and safety (by monitoring AEs) of the IP allo-APZ2-CVU, administered topically on target wounds of patients with therapy-resistant non-healing CVU compared to placebo.

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 Timeline

• Study First Posted: 2024-12-16
• Last Update Posted: 2025-05-14

Recruitment & Eligibility

• Status: Authorised, recruiting
• Sex: Not specified
• Target Recruitment: 230

Inclusion Criteria

Patients at least 18 years old

Chronic venous leg ulcer at lower leg and/or ankle region that has not been present longer than 15 years, diagnosed by Doppler-Duplex sonography, ankle brachial index (ABI, 0.9-1.3; optionally, in case ABI > 1.3 or not measurable: toe brachial index (TBI) ≥0.7)), physical examination and dermatological review

Wound size at V1 and V2 between 1 and 25 cm2 as measured by standardized photography

If patients have 2 or more ulcers at the same extremity, the target ulcer (defined at V2) has to be separated from the other ulcers with a bridge of epithelialized skin at least 1 cm wide

Body mass index between 15 and 50 kg/m²

Patients able to understand the nature of the study and able to provide written informed consent prior to any clinical trial procedures

Women of childbearing potential must have a negative urine pregnancy test at Visit 1

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

Evidence of the ulcer extending to the underlying muscle, tendon, or bone

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

Pregnant or lactating women

Known hypersensitivities to the active substance or to any of the excipients in the IP or the placebo

Surgical procedure affecting the CVU, such as bypass or mesh graft performed within two months prior to Visit 1

Current or previous (within 30 days of enrollment) treatment with another IP, or participation in another clinical trial, including follow-up phase

Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion)

Employees of the sponsor, or employees or relatives of the investigator(s)

Uncontrolled Diabetes mellitus i.e. Hemoglobin A1c (HbA1c) >9.0% (75 mmol/mol) (measured by blood test)

Peripheral Artery Disease including claudication with need of treatment or intervention

Acute deep vein thrombosis diagnosed within 30 days before V1, or untreated deep vein thrombosis

Wounds showing size reduction of more than 40% at Visit 2 compared to Visit 1

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

Acute wound infection of ulcer requiring treatment as judged clinically

Current use of medications that are known to influence wound healing i.e. systemic immunosuppressives, cytotoxic medicinal products, systemic steroids (above Cushing-threshold level) at investigator´s discretion

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Efficacy: Complete wound closure at Week 18 already persisting for at least two weeks		Efficacy: Complete wound closure at Week 18 already persisting for at least two weeks
Safety: Adverse events		Safety: Adverse events

Secondary Outcome Measures

Name	Time	Method
Complete wound closures at each post-baseline follow-up visit		Complete wound closures at each post-baseline follow-up visit
Wound size change in percent at each post-baseline follow-up visit		Wound size change in percent at each post-baseline follow-up visit
Quality of wound healing at each post-baseline follow-up visit		Quality of wound healing at each post-baseline follow-up visit
Assessment of Quality of Life using the Wound-Quality of Life Questionnaire (W-QoL) as well as the EQ-5D-5L Questionnaire and the SF-36 at V8, V11, V14, V15, V16, V17		Assessment of Quality of Life using the Wound-Quality of Life Questionnaire (W-QoL) as well as the EQ-5D-5L Questionnaire and the SF-36 at V8, V11, V14, V15, V16, V17
Pain assessment as per numerical rating scale (NRS) on each post-baseline follow-up visit		Pain assessment as per numerical rating scale (NRS) on each post-baseline follow-up visit
Duration of wound closure		Duration of wound closure
Recurrence of the wound		Recurrence of the wound
Time to complete wound closure		Time to complete wound closure
Physical examination and vital signs at V14		Physical examination and vital signs at V14
Assessment of immunogenicity		Assessment of immunogenicity

Trial Locations

Locations (82)

Centrum Oosterwal; 🇳🇱 Alkmaar, Netherlands

Rijnstate Ziekenhuis Stichting; 🇳🇱 AD Arnhem, Netherlands

Bravis Ziekenhuis; 🇳🇱 Bergen Op Zoom, Netherlands

Medical University Of Vienna; 🇦🇹 Vienna, Austria

Medizinische Universität Graz; 🇦🇹 Graz, Austria

ÖGK Hanusch-Krankenhaus; 🇦🇹 Wien, Austria

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris, France

Centre Hospitalier Groupe Hospitalier De La Rochelle Re Aunis; 🇫🇷 La Rochelle, France

Centre Hospitalier Departemental Vendee; 🇫🇷 La Roche Sur Yon Cedex 9, France

Centre Hospitalier Universitaire De Montpellier; 🇫🇷 Montpellier Cedex 5, France

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Centrum Oosterwal

🇳🇱Alkmaar, Netherlands

Michael Cornelis Mooij

Site contact

+31725157744

r.pullens@centrum-oosterwal.nl