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.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 105
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years at the time of consent,
- •The patient's psychophysical and legal ability to give informed consent to participate in the study,
- •Signing the informed consent document for participation in the study,
- •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),
- •Duration of the ulcer not less than 6 weeks,
- •Presence of a wound with an area of 1-25 cm² (after wound debridement),
- •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,
- •Glycated hemoglobin (HbA1c) < 11%,
- •General health status of the patient, which in the investigator's opinion allows participation in all study procedures,
- •Use of the wound offloading method recommended by the investigator,
- •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).
排除标准
- •Etiology of the ulcer other than diabetic foot syndrome,
- •Presence of an active infection in the wound at the time of inclusion in the study,
- •Wound area <1 cm² or >25 cm²,
- •The patient was enrolled in another clinical trial within the 4 weeks preceding the qualification for this study.
- •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,
- •Presence of an active phase of Charcot joint,
- •Suspected osteitis and/or osteomyelitis within the study wound,
- •Revascularization procedure on the affected lower limb within 3 months prior to study inclusion or planned revascularization procedure,
- •Chronic kidney disease with GFR < 20 ml/min,
- •Pregnancy and lactation,
- •Allergy to thrombin,
- •Active venous thrombosis,
- •Systemic diseases in the exacerbation stage (acute or decompensated), including heart, kidney, and liver diseases,
- •Active alcohol disease or addiction to psychoactive substances,
- •Allergies to dressing materials used in the study,
- •Oral/intravenous antibiotic therapy at the time of inclusion in the study,
- •Patient undergoing immunosuppressive therapy, including corticosteroid therapy (within 30 days prior to study inclusion),
- •Active cancer or cancer disease in the last 5 years, excluding locally malignant cancers not involving foot tissues,
- •Presence of known clinically active, uncontrolled infections such as hepatitis B, hepatitis C, HIV, and venereal disease (syphilis),
- •Significant features of malnutrition additionally impairing the healing process, regardless of the cause (albumin < 2.5 g/dl and total protein < 5 g/dl),
- •Hemoglobin levels < 9 g/dl,
- •Serum transaminase (alanine and aspartate) activity higher 3x the upper limit of normal (locally).
研究组 & 干预措施
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.
干预措施: A - Allogenic ADSC cells in fibrin solution - two times administration ADSC/ASC (Biological)
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.
干预措施: B - Allogenic ADSC cells in fibrin solution - one time administration of ADSC/ASC, one time of placebo (Biological)
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.
干预措施: C - Standard care in diabetic foot ulcer with aplication of fibrin gel to cover wound surface. (Other)
结局指标
主要结局
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.
时间窗: 6 weeks after the first administration
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.
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.
时间窗: 6 weeks after the first administration
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.
次要结局
- 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)(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.(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 .(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.(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.(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.(6 weeks after the first administration and through study completion, an average of 1 year)