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 a10ß1-selected mesenchymal stem cells (XSTEM-VLU) in patients with difficult-to-heal venous leg ulcers
- Conditions
- Difficult-to-heal venous leg ulcersMedDRA version: 21.1Level: LLTClassification code 10047260Term: Venous ulcerationSystem Organ Class: 10040785 - Skin and subcutaneous tissue disordersTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2022-000492-39-SE
- Lead Sponsor
- Xintela AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 12
For inclusion in the study, patients must fulfil the following criteria:
1.Willing and able to give written informed consent for participation in the study.
2.Male or female patient aged =18 years at the time of the screening visit (Visit 1).
3.BMI =18.5 and =40.0 kg/m2.
4.Wound located on the lower part of the lower limb, with a predominant venous component.
5.Target wound has failed to heal despite standard wound care including compression therapy for a minimum of 6 weeks prior to the screening visit (Visit 1), as judged by the Investigator.
6.Patient who has been compliant to their prescribed compression therapy over the (at least) 6 weeks prior to the screening visit (Visit 1), as judged by the Investigator.
7. A surface area of the target wound of =2.00 and =40.00 cm2 measured using the SeeWound (or other wound planimetry measure) after standard wound care attention at the screening visit (Visit 1).
8.WOCBP must practice abstinence (only allowed when this is the preferred and usual lifestyle of the patient) or agree to use a highly effective method of contraception with a failure rate of <1 % to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]) from at least 4 weeks prior to ATIMP administration to 3 months after ATIMP administration. Female patients must refrain from donating eggs from the date of ATIMP administration until 3 months after ATIMP administration. Any male partner of a female study patient must agree to use a condom during the same period.
Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or post-menopausal defined as 12 months of amenorrhea.
Male patients must be willing to use condoms, be vasectomised or practice abstinence (only allowed when this is the preferred and usual lifestyle of the patient) to prevent pregnancy and drug exposure of a partner, as well as refrain from donating sperm from the date of ATIMP administration until 3 months after ATIMP administration. Any female partner of a male study patient must agree to use a contraceptive method with a failure rate of < 1 %, as described above, to prevent pregnancy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
Patients must not enter the study if any of the following exclusion criteria are fulfilled:
1.History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient’s ability to participate in the study.
2.Any planned major surgery during the study.
3.Signs or symptoms of clinically significant ongoing infection (in the target wound) requiring anti-microbial treatment (including antibiotics) during the screening period (from Visit 1) until randomisation (Visit 5), as judged by the Investigator. Topical anti-microbial therapy being part of a patient’s standard wound care is allowed prior to Visit 5.
4.History of any autoimmune disease, such as but not limited to systemic lupus erythematosus, Addison’s disease, Crohn’s disease and type I diabetes mellitus.
5.B-HbA1C value =52 mmol/mol at the time of the screening visit (Visit 1).
6.Plaque psoriasis or any other skin disease that could interfere with the outcome of the study, as judged by the Investigator.
7. Ankle-brachial index <0.7 at the screening visit (Visit 1).
8.History of any malignancy within the past 5 years.
9.Target wound diagnosed as a malignant wound, neuropathic wound, pressure wound or osteomyelitis.
10.Non-target wound within 2 cm of the target wound.
11.Current use of systemic corticosteroids which in the opinion of the Investigator could interfere with the quality of, or the healing properties of the skin.
12.Patients who are immunocompromised due to disease (e.g., HIV) or for other reasons such as the use of systemic immunosuppressants.
13.Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibodies and/or HIV.
14.History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to XSTEM-VLU, DMSO, dextran or any other components of the therapy media.
15.Patients who are pregnant, currently breastfeeding, or intend to become pregnant during the first 3 month after ATIMP administration.
16.Planned treatment or treatment with another investigational drug from signing of the informed consent until Visit 16.
17.Medical, psychiatric, cognitive, or other conditions that may compromise the patient’s ability to understand the patient information, give informed consent, comply with the study protocol or complete the study, as judged by the Investigator.
Additional exclusion criterion evaluated at Visit 5 (pre-dose):
18.A surface area of the target wound of <1.50 or >50.00 cm2 measured using SeeWound (or other planimetry measure).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To characterise the safety and tolerability of a single dose of XSTEM-VLU and vehicle as add on to standard wound care in patients with difficult-to-heal venous leg ulcers.;Secondary Objective: To assess preliminary efficacy of a single dose of XSTEM-VLU and vehicle as add on to standard wound care in patients with difficult-to-heal venous leg ulcers.;Primary end point(s): -Frequency, seriousness and intensity of adverse events (AEs)<br>-Local tolerability, including need for debridement and clinical signs of wound infection<br>-Clinically significant changes in vital signs, electrocardiogram (ECG), safety laboratory measurements (haematology, clinical chemistry, coagulation) and physical examination findings<br><br>;Timepoint(s) of evaluation of this end point: Regularly throughout the study, from dose until end of study visit.
- Secondary Outcome Measures
Name Time Method