Evaluation of Autologous Adipose Tissue-Derived Stromal Vascular Fraction Cells in Refractory Diabetic Foot Ulcers: A Phase II Multicenter Study

Trial ID: 2024-516342-19-00
Sponsor: Centre Hospitalier Regional De Marseille

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Diseases & Conditions

Diabetic foot

Objectives

The primary objective of this study is to evaluate the **effectiveness** of local injection of autologous stromal vascular fraction (SVF) derived from adipose tissue in the treatment of diabetic foot ulcers that are refractory to conventional treatment, as recommended by the International Working Group, at week 20. This is clinically relevant as diabetic foot ulcers are a common complication of diabetes, often leading to severe outcomes such as infection and amputation. The use of SVF, a cell therapy derived from the patient's own adipose tissue, represents a novel therapeutic approach that could potentially enhance healing and reduce the burden of this condition.

Participants

The sponsor does not provide information regarding the total number of participants in this clinical trial. The study population includes both **male** and **female** subjects aged 18 years and older, diagnosed with either type 1 or type 2 diabetes mellitus. Participants must have a **diabetic foot ulcer** (DFU) classified as grade I-C or II-C according to the University of Texas Diabetic Wound Classification, with a surface area between 1 and 15 cm² after debridement. The ulcers must be refractory to conventional treatment for at least two months and located on a toe or foot. Subjects are required to have a body mass index (BMI) of at least 18.5 kg/m² to ensure sufficient fat tissue for the study. Participants must be in good overall health, as determined by history and clinical examination, and must be willing to adhere to the study's discharge system and dressing requirements. Women of childbearing potential must have a negative pregnancy test and use reliable contraception throughout the study. The study does not include a vulnerable population, and all participants must be affiliated with social security. Key lifestyle considerations include the requirement for participants to maintain prescribed dressing and discharge systems daily.

Plans and Procedures

The clinical trial is designed to evaluate the effectiveness of **autologous adipose tissue-derived stromal vascular fraction cells** in the treatment of **diabetic foot ulcers**. This is a Phase II, open-ended, multi-centre study. The trial will involve a randomized, controlled design to ensure the reliability of the results. The study is expected to commence on January 9, 2024, and conclude by March 9, 2028, with the primary endpoint being the percentage of wounds completely healed by week 20 post-injection.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as the presence of neuropathy and a satisfactory arterial blood supply to the lower limb. The inclusion visit will also involve obtaining informed consent and conducting necessary baseline assessments. Following the initial visit, participants will receive the investigational product, SVF, administered as a **suspension for injection** via transdermal use. The maximum daily dose is 15 ml, with a total treatment period of one day.

Subsequent follow-up visits will be scheduled to monitor the participants' progress and assess the healing of the ulcers. These visits will include clinical evaluations and any necessary adjustments to the treatment protocol. The end-of-study visit will occur at the conclusion of the 20-week period, where the final assessment of wound healing will be conducted.

Participant involvement is expected to last approximately 20 weeks, from the initial screening to the end-of-study visit. Conditions that may lead to early termination from the study include the development of clinical signs of local wound infection or failure to adhere to the study protocol, such as not wearing the prescribed dressing or discharge system. The trial aims to provide valuable insights into the potential benefits of SVF in treating diabetic foot ulcers, contributing to the advancement of therapeutic options for this condition.

Treatment

The clinical trial involves the use of an **experimental medication** known as SVF, which is a **suspension for injection**. The active substance in SVF is **autologous adipose tissue-derived stromal vascular fraction cells**, classified as a structurally diverse substance used in cell therapy. The pharmaceutical form of SVF is specifically designed for **transdermal use**. The maximum daily dose and total dose amount are both set at 15 ml, with the treatment period limited to one day. The administration of SVF is intended to evaluate its effectiveness in treating diabetic foot ulcers that are refractory to conventional treatments.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapies as a comparator to assess the efficacy of the SVF treatment. These therapies are not experimental and are part of the conventional treatment protocols for diabetic foot ulcers. The study does not include the use of a placebo. Participant compliance with the dosing schedule will be monitored to ensure adherence to the treatment protocol. The trial aims to provide insights into the potential benefits of SVF in the management of diabetic foot ulcers, with a focus on safety and efficacy outcomes.

Efficacy

Efficacy in this clinical trial will be assessed by evaluating the effectiveness of local injection of **autologous adipose tissue-derived stromal vascular fraction cells** in the treatment of diabetic foot ulcers. The primary endpoint for efficacy assessment is the percentage of wounds completely healed by week 20 post-injection. This endpoint will be measured to determine the success of the treatment in achieving complete wound healing within the specified timeframe. The trial is designed to assess the treatment's efficacy in patients with diabetic foot ulcers that are refractory to conventional treatment, as defined by the International Working Group. The study will follow a structured schedule to collect and analyze data at the designated timepoint of week 20, ensuring a comprehensive evaluation of the treatment's impact on wound healing.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Informed Consent Form Information and Signature
Female or male patient 18 years of age or older
Type 1 or 2 diabetes mellitus patient with 10% HbA1C less than 1 month old (if this result is not available at the inclusion visit, analysis should be done during the 15-day assessment period)
Affiliation to social security.
Patient willing to wear the discharge system daily and the prescribed dressing throughout the study.
Patient with BMI 18.5 Kg/m² (in order to have sufficient fat tissue)
Good overall condition, based on history and clinical examination
Women of childbearing age must have a negative pregnancy test (serum or urine) pregnancy test (detection threshold (sensitivity): 25 mIU hCG/ml). Patients of both sexes must use a reliable method of contraception in accordance with CTFG. In addition, contraception must be maintained throughout the treatment until the end of systemic exposure.
UPD with "satisfactory" arterial blood supply to the lower limb bearing the target lesion: ischemia grade 0, 1 and 2 according to WIfI classification (Mills JL Sr, 2014).
UPD grade I-C or II-C as defined by the University of Texas Diabetic Wound Classification. University of Texas Appendix 1
Neuropathy confirmed by loss of protective sensation on monofilament test (Semmes-Weinstein 5.07 monofilament).
UPD located on a toe or on the foot
UPD with a surface area of between 1 and 15 cm2 after debridement
UPD refractory to conventional treatment for at least 2 months, including an appropriate wound care protocol.
No clinical signs of local wound infection (whether target UPD or not) localized to the lower limbs (as defined by IDSA/IWGDF infection criteria).

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Exclusion Criteria

Pregnant or breastfeeding women or women of childbearing age without effective contraception
Known hypersensitivity to human albumin.
Surgical revascularization or surgery of the lower limbs within the last month
Ischemic event (stroke, myocardial infarction) within 3 months of inclusion
Patient with renal failure requiring dialysis
Systemic infection not controlled by appropriate antibiotic treatment
Patient with documented osteomyelitis
Patient with active neoplasia, treated by radiotherapy, chemotherapy, hormone therapy or immunosuppressive therapy.
Patient treated for a chronic pathology requiring high-dose corticosteroid therapy (≥ 40 mg/d prednisolone or equivalent).
Patient with serious pathology that could lead to premature discontinuation of the study.
Patients with a history of coagulation disorders contraindicating surgical intervention
Positive markers of the following active infectious diseases: Infection with immunodeficiency viruses HIV 1 and HIV 2; HTLV I infection; Hepatitis C virus infection Hepatitis B virus infection; Hepatitis C virus infection; Syphilis infection.
Congenital or acquired immune deficiency.
UPD with ischemia grade 3 according to WIfI classification (Mills JL Sr, 2014)
UPD with surgery or revascularization planned at any time during the time of the study
deep UPD defined as stage III by the University of Texas Diabetic Wound Classification (Appendix 1)
UPD clinically infected, as defined by IDSA/IWGDF infection criteria
UPD whose surface is covered by more than 20% black necrosis after debridement
UPD located on the scar of the amputation stump
UPD with carcinomatous degeneration
Reduction ≥ 30% of wound surface measured after the 15 days (Urgostart and adapted offloading system) compared with wound surface area measured at the inclusion visit (on the basis of wound surface measurement) [criterion assessed after the 15-day evaluation period, on the day of treatment].
Adults protected by law (under guardianship or curatorship)
Minors
People staying in a health or social care establishment
People in emergency situations
Persons not covered by a social security scheme
Adults deprived of their freedom by administrative or judicial decision, or subject to a legal protection measure, or who are unable to express their consent
Patient participating in another clinical trial
Absence or refusal of informed consent