A Study of XSTEM-VLU in Patients With Difficult-to-heal Venous Leg Ulcers

Study Overview
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Brief Summary
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The aim of the study is to assess safety, tolerability and preliminary efficacy of XSTEM-VLU when administered as a single topical dose to patients with difficult-to-heal venous leg ulcers. The study is randomised and the patients will receive either XSTEM-VLU or vehicle as add on to standard wound care. The patients will be followed weekly for 10 weeks after treatment. At 6 months after treatment, the patients will return to the clinic for an end-of-study visit.

Official Title
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A Multi-centre, Randomised, Single-blind Phase I/IIa Study to Evaluate the Safety, Tolerability and Efficacy of a Single Topical Dose of Allogeneic Integrin α10β1-selected Mesenchymal Stem Cells (XSTEM-VLU) in Patients With Difficult-to-heal Venous Leg Ulcers

Conditions
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Venous Leg Ulcer

Intervention / Treatment
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* Biological: XSTEM-VLU
* Other: Vehicle


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Written informed consent for participation in the study Male or female patient aged ≥18 years BMI ≥18.5 and ≥35.0 kg/m2 Lower leg wound due to venous insufficiency Target wound has failed to heal despite standard wound care including compression therapy for a minimum of 6 weeks Patient who has been compliant to their prescribed compression therapy over the (at least) 6 weeks prior to screening A surface area of the target wound of ≥3 and ≤40 cm2 Major Exclusion Criteria: Signs or symptoms of clinically significant ongoing infection requiring intravenous or oral systemic treatment History of autoimmune disease, such as but not limited to systemic lupus erythematosus, Addison's disease, Crohn's disease and type I diabetes mellitus B-HbA1C value ≥52 mmol/mol Plaque psoriasis or any other skin disease that could interfere with the outcome of the study Arterial insufficiency History of any malignancy within the past 5 years Target wound diagnosed as a malignant wound, neuropathic wound, pressure wound or osteomyelitis Concomitant treatment that may interfere with the stem cell treatment Patients who are immunocompromised due to disease or for other reasons such as the use of systemic immunosuppressants

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XSTEM-VLU<br>Single topical dose of XSTEM-VLU | Biological: XSTEM-VLU<br>* XSTEM-VLU is an allogeneic, adipose tissue-derived, integrin alpha10beta1-selected and expanded mesenchymal stem cell (MSC) product for the treatment of venous leg ulcers.<br>|
| Placebo Comparator: Vehicle<br>Single topical dose of CryoStor CS10 | Other: Vehicle<br>* CryoStor CS10 cryomedium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Adverse events (AEs) | Frequency, seriousness and intensity of AEs assessed by the Common Terminology Criteria for Adverse Events (CTCAE) | From study start to 6 months after dosing | 
| Safety and tolerability: Local tolerability | Local tolerability evaluated by direct inspection by need for debridement (Yes/No) and clinical signs of wound infection (Yes/No) | From study start to 6 months after dosing | 
| Safety and tolerability: Number of participants with abnormal 12-lead electrocardiogram (ECG) | Abnormal findings assessed by the Investigator as clinically significant will be reported as AEs. | From study start to 6 months after dosing | 
| Safety and tolerability: Number of participants with abnormal vital signs | Vital signs include blood pressure, pulse and body temperature. Abnormal findings assessed by the Investigator as clinically significant will be reported as AEs. | From study start to 6 months after dosing | 
| Safety and tolerability: Number of participants with abnormal laboratory test results | Laboratory tests include clinical chemistry, haematology and coagulation parameters. Abnormal values assessed by the Investigator as clinically significant will be reported as AEs. | From study start to 6 months after dosing | 
| Safety and tolerability: Number of participants with abnormal physical examination findings | Abnormal findings assessed by the Investigator as clinically significant will be reported as AEs. | From study start to 6 months after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary efficacy: Wound area reduction (absolute and percentage) compared to baseline |  | From study start to 6 months after dosing | 
| Preliminary efficacy: Proportion of patients with re-epithelialization of >=95% and >=50% of the wound area measured at baseline |  | From study start to 6 months after dosing | 
| Preliminary efficacy: Time to re-epithelialization of >=95% and >=50% of the wound area measured at baseline |  | From study start to 6 months after dosing | 
| Preliminary efficacy: Pain for target wound and the affected leg using Visual Analogue Scale (VAS) | The VAS consists of a 100 mm line from no pain (0 mm) to worst possible pain (100 mm). | From study start to 6 months after dosing | 
| Preliminary efficacy: Scar formation assessed by the Patient and Observer Scar Assessment Scale (POSAS) | The POSAS is divided into two scales (for patient and for observer), each with six items scored numerically (1 -10). The lowest score 1 corresponds to normal skin. | At week 10 and at 6 months after dosing |