Evaluation of the Safety and Efficacy of Live ASCs in the Treatment of Diabetic Foot (FOOTCELL) (FOOTCELL)

Evaluation of the Safety and Efficacy of an Advanced Therapy Medicinal Product Containing Live ASCs in the Treatment of Diabetic Foot Syndrome - a Double-blind, Randomized Study.

The goal of this study is to investigate the safety and efficacy of allogenic mesenchymal stem cells isolated from adipose tissue as the treatment for chronic wounds in diabetic foot syndrome in a double-blinded three armed setup.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Biological: A - Allogenic ADSC cells in fibrin solution - two times administration ADSC/ASC; Biological: B - Allogenic ADSC cells in fibrin solution - one time administration of ADSC/ASC, one time of placebo; Other: C - Standard care in diabetic foot ulcer with aplication of fibrin gel to cover wound surface.

Detailed Description

Patients will be randomized and assigned to one of three study groups, and will receive according IMP solutions: 1) two doses of cell solution; 2) one dose of cell solution and one dose of placebo solution; 3) two doses of placebo solutions. During the study Patients will attend to weekly visits for routine monitoring and SOC treatment. The IMP solutions will be administered in two weeks intervals, on day 0 and day 14 of the treatment, and the control visits are scheduled on days 7, 21, 28, 35 and 42 - for a total of 7 visits during the active phase of the study. The follow-up visits will be performed 8, 26 and 52 weeks after the last visit in the active phase (day 42).

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Beata Mrozikiewicz-Rakowska, Assoc.Prof.; Phone Number: +48 225690529; Email: klinendo@bielanski.med.pl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age >18 years at the time of consent,
2. The patient's psychophysical and legal ability to give informed consent to participate in the study,
3. Signing the informed consent document for participation in the study,
4. Ulcer classified as diabetic foot syndrome (DFS) of neuropathic and/or neuroischemic etiology corresponding to grade IA/IIA and IC/IIC according to the University of Texas classification (Appendix E),
5. Duration of the ulcer not less than 6 weeks,
6. Presence of a wound with an area of 1-25 cm² (after wound debridement),

7. Satisfactory blood supply to the wound area:

   • assessed using transcutaneous oxygen pressure measurement, if its value is not less than 30 mmHg,
   • or measurement of systolic blood pressure at the posterior tibial artery and/or dorsalis pedis artery, which is not less than 50 mmHg, to exclude patients who require revascularization therapy,
8. Glycated hemoglobin (HbA1c) < 11%,
9. General health status of the patient, which in the investigator's opinion allows participation in all study procedures,
10. Use of the wound offloading method recommended by the investigator,

11. Use of effective contraception methods to avoid pregnancy (see also Appendix F) and/or based on the following criteria:

    • a woman who is unable to have children (after a hysterectomy or bilateral oophorectomy or post-menopause, defined as a period of at least 12 months since the last menstrual period) is exempt from pregnancy tests,
    • a woman able to have children with a negative pregnancy test result before the administration of the investigational product on the first day and who agrees to periodic pregnancy testing according to the study protocol and to use highly effective contraceptive methods for one month after the end of the active phase of the study (from V6), or two months after the last administration of the investigational drug (from V2).

Exclusion Criteria:

1. Etiology of the ulcer other than diabetic foot syndrome,
2. Presence of an active infection in the wound at the time of inclusion in the study,
3. Wound area <1 cm² or >25 cm²,
4. The patient was enrolled in another clinical trial within the 4 weeks preceding the qualification for this study.

5. Clinically significant limb ischemia:

   • assessed using transcutaneous oxygen pressure measurement, if its value is lower than 30 mmHg
   • or measurement of systolic blood pressure at the posterior tibial artery and/or dorsalis pedis artery, if it is lower than 50 mmHg,
6. Presence of an active phase of Charcot joint,
7. Suspected osteitis and/or osteomyelitis within the study wound,
8. Revascularization procedure on the affected lower limb within 3 months prior to study inclusion or planned revascularization procedure,
9. Chronic kidney disease with GFR < 20 ml/min,
10. Pregnancy and lactation,
11. Allergy to thrombin,
12. Active venous thrombosis,
13. Systemic diseases in the exacerbation stage (acute or decompensated), including heart, kidney, and liver diseases,
14. Active alcohol disease or addiction to psychoactive substances,
15. Allergies to dressing materials used in the study,
16. Oral/intravenous antibiotic therapy at the time of inclusion in the study,
17. Patient undergoing immunosuppressive therapy, including corticosteroid therapy (within 30 days prior to study inclusion),
18. Active cancer or cancer disease in the last 5 years, excluding locally malignant cancers not involving foot tissues,
19. Presence of known clinically active, uncontrolled infections such as hepatitis B, hepatitis C, HIV, and venereal disease (syphilis),
20. Significant features of malnutrition additionally impairing the healing process, regardless of the cause (albumin < 2.5 g/dl and total protein < 5 g/dl),
21. Hemoglobin levels < 9 g/dl,
22. Serum transaminase (alanine and aspartate) activity higher 3x the upper limit of normal (locally).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A - ADSC/ASC cells in fibrin solution - two times administration of ADSC/ASC; Application of allogeneic ADSC stem cells in fibrin gel, to cover wound surface with thin cells layer. Therapy is based on standard of care procedure for diabetic foot ulcer treatment combined with application of allogeneic ADSC stem cells in fibrin solution onto the wound surface.	Biological: A - Allogenic ADSC cells in fibrin solution - two times administration ADSC/ASC; ADSC/ASC will be administered twice, at two-week intervals - during V0 and V2 visits The first dose will be administered one week after the randomisation visit. Control visits after administration will be performed every week, up to V6 visit (up to 6 weeks after V0).
Experimental: B - ADSC/ASC cells in fibrin solution - one administration of ADSC/ASC, one administration placebo; Application of allogeneic ADSC stem cells and placebo in fibrin gel, to cover wound surface with thin cells layer. Therapy is based on standard of care procedure for diabetic foot ulcer treatment combined with application of allogeneic ADSC stem cells and placebo in fibrin solution onto the wound surface.	Biological: B - Allogenic ADSC cells in fibrin solution - one time administration of ADSC/ASC, one time of placebo; ADSC/ASC will be administered once, at the time of the second application patients will receive a placebo - during V0 and V2 visits The first dose will be administered one week after the randomisation visit. Control visits after administration will be performed weekly, up to V6 visit (up to 6 weeks after V0)
Placebo Comparator: C - Standard care in diabetic foot ulcer with aplication of fibrin gel to cover wound surface.; Standard of care procedure for diabetic foot ulcer with aplication of fibrin gel to cover wound surface. Application of fibrin gel to cover wound surface.	Other: C - Standard care in diabetic foot ulcer with aplication of fibrin gel to cover wound surface.; Placebo will be administered twice, at two-week intervals - during V0 and V2 visits The first dose will be administered one week after the randomisation visit. Control visits after administration will be performed every week, up to V6 visit (up to 6 weeks after V0).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in wound size (%) at 6 weeks after first study treatment administration compared to baseline with the actual wound size measured by the independent assessor.	Percentage change in wound size, measured by an independent assessor using a standardized wound area measurement method. The calculation is based on the difference between the baseline wound size and the wound size at 6 weeks, expressed as a percentage of the baseline value.	6 weeks after the first administration
Type, frequency and severity of adverse events (assessed according CTCAE v5.0); change from baseline of laboratory parameters and selected vital signs of the participants.	Adverse events will be assessed based on type, frequency, and severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Changes from baseline in laboratory parameters and selected vital signs will be evaluated using standardized clinical measurement methods.	6 weeks after the first administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early efficacy of the allogenic ADSC/ASC defined as percentage of patients with significant clinical success defined as complete wound closure (100% epithelialization), or partial epithelialization of the wound (>50% epithelialization)	The percentage of patients achieving significant clinical success, defined as either complete wound closure (100% epithelialization) or partial epithelialization of the wound (>50%). Wound epithelialization will be assessed using standardized wound assessment criteria by an independent assessor.	6 weeks after the first administration
Long-term efficacy of the allogenic ADSC/ASC defined as percentage of patients with significant clinical success defined as complete wound closure (100% epithelialization), or partial epithelialization of the wound (>50% epithelialization) over time.	The percentage of patients achieving significant clinical success, defined as either complete wound closure (100% epithelialization) or partial epithelialization of the wound (>50%), assessed over time. Wound epithelialization will be evaluated using standardized wound assessment criteria by an independent assessor at predefined time points.	Through study completion, an average of 1 year
The dynamics of wound healing defined as the time required for patients to reach the wound size reduction thresholds: 50% reduction of the wound; maximum reduction of the wound area (%); complete wound healing .	The time required for patients to achieve predefined wound size reduction thresholds, including 50% wound size reduction, maximum wound area reduction (percentage), and complete wound healing (100% epithelialization). Wound size will be measured using standardized wound assessment methods by an independent assessor at predefined time points.	6 weeks after the first administration and through study completion, an average of 1 year
Absolute change in the wound-associated pain perception over time assessed by the patient using visual analogue scale.	Evaluation of the wound-associated pain, assessed by the patient using visual analogue scale. The minimum value is 0 and means "no pain" and the maximum value is 10 and means "the worst possible pain". The lower value the better outcome.	6 weeks after the first administration and through study completion, an average of 1 year
Additional safety parameters such as wound infection requiring antibiotic treatment expressed as total number of patients, and number of antibiotic therapies per patient.	The total number of patients with wound infections requiring antibiotic treatment and the number of antibiotic therapy courses per patient. Infections will be assessed based on clinical criteria and standard medical guidelines.	6 weeks after the first administration and through study completion, an average of 1 year .
Changes in quality of life parameters assessed by the dedicated QoL questionnaire.	Evaluation of the patient's quality of life, assessed by the dedicated QoL questionnaire. The QoL questionnaire consists of 10 questions. Each question is scored 1 to 5. The minimum score is 10 and it means "the best possible state of health", and the maximum score is 50, which means ,,the worst possible state of health".	6 weeks after the first administration and through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the additional safety and efficacy parameters such as the percentage of patients requiring lower or upper limb amputation or the percentage of patients experiencing CVD events (CVD death, hospitalization for CVD reason)	The percentage of patients requiring lower or upper limb amputation and the percentage of patients experiencing cardiovascular events (CVD death, hospitalization for CVD reasons). Events will be assessed based on clinical diagnosis and medical records.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Collaborators: Medical Research Agency, Poland
• Investigators: Principal Investigator: Beata Mrozikiewicz-Rakowska, Assoc.Prof., Bielanski Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 8, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: diabetes; adipose-derived mesenchymal stem cells; chronic wounds; foot ulcer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Pharmaceutical Solutions
• Other Study ID Numbers: FOOTCELL

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