Miro3D Wound Matrix for Treatment of Diabetic Foot Ulcers

This is a prospective, multicenter, open-label, randomized controlled trial designed to evaluate the safety and effectiveness of the Miro3D Wound Matrix in the treatment of chronic, non-healing diabetic foot ulcers (DFUs).

Diabetic foot ulcers represent a significant clinical and economic burden and are associated with increased risk of infection, hospitalization, and amputation. Despite adherence to standard of care (SOC), including offloading, debridement, infection control, and moisture management, a substantial proportion of DFUs fail to achieve complete healing. This study aims to assess whether adjunctive treatment with Miro3D Wound Matrix can improve healing outcomes compared to SOC alone.

Miro3D Wound Matrix is a sterile, acellular, three-dimensional scaffold derived from porcine liver tissue. The matrix is designed to provide a structural environment that supports tissue regeneration and wound healing. The product is applied topically to the wound following appropriate wound bed preparation.

Approximately 180 adult subjects with Wagner Grade 1 or 2 diabetic foot ulcers will be enrolled across up to 20 clinical sites in the United States. Subjects must have ulcers present for at least 4 weeks but less than 12 months and must demonstrate less than 25% reduction in wound area during a two-week screening period under standard of care.

Following screening, eligible subjects will be randomized in a 1:1 ratio to one of two treatment arms: treatment with Miro3D Wound Matrix in addition to standard of care, or standard of care alone.

Standard of care will include sharp debridement, offloading using a protocol-defined device, and appropriate moisture-retentive dressings.

Subjects will be evaluated at weekly intervals for up to 12 weeks. At each visit, assessments will include wound measurement, photographic documentation, infection status, pain assessment using the Numeric Pain Rating Scale (NPRS), and monitoring of adverse events. At select sites, additional exploratory imaging assessments may be performed, including near-infrared tissue oxygenation and fluorescence imaging.

The primary endpoints of the study are complete wound closure at 12 weeks, defined as full re-epithelialization without drainage or need for dressing, with closure confirmed at a single healing confirmation visit conducted two weeks after complete closure is initially documented, and percentage area reduction of the target ulcer over the study period. Secondary endpoints include change in pain associated with the ulcer and the incidence and frequency of adverse events. Exploratory endpoints will assess spatial and temporal changes in tissue oxygenation and fluorescence imaging characteristics at technology-enabled sites.

The study will use a Bayesian adaptive statistical framework, incorporating prior information and observed data to estimate treatment effects. Interim analyses may be conducted to evaluate efficacy, safety, and sample size assumptions.

This study is intended to generate clinical evidence supporting the use of Miro3D Wound Matrix as an adjunctive therapy for improving healing outcomes in patients with chronic diabetic foot ulcers.

Inclusion criteria

• Subjects 18 years of age or older.
• Subject history of Type I or Type II Diabetes Mellitus requiring treatment with oral medications and/or insulin replacement therapy.
• A diabetic foot ulcer present for greater than 4 weeks (documented in the medical record) but less than 12 months duration if being treated with active SOC.
• Objectively, less than 25% wound area reduction in the two-week screening period prior to randomization.
• Study ulcer is a minimum of 1.0cm2 and a maximum of 25 cm2 post-debridement at first treatment visit.
• Index ulcer and/or index ulcer limb may have had prior infection, but infection(s) must be adequately treated and controlled as defined by IDSA Guidelines Grade level 1.
• The subject is able and willing to follow the protocol requirements.
• Subject has signed informed consent.

Subjects with the following ulcer:

A. Presence of a diabetic foot ulcer Wagner 1 or 2 grade at the first screening visit on any aspect of the foot, provided 50% of the wound sits below the level of the malleolus. This includes DFUs as a result of open amputation sites and surgical wound dehiscence as long as all other criteria are met. [NOTE: If two or more DFUs are present with the same grade, the index ulcer is the largest ulcer and the only one evaluated in the study. Index ulcer must be more than 2 cm distant apart.]

• Adequate circulation to the affected foot as demonstrated by a dorsum transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg; Toe pressures >50mmHg; an ABI between 0.7 and ≤ 1.3, or TBI of >0.6 within 3 months of the first Screening Visit.
• Negative pregnancy test for females of childbearing potential (e.g., not post- menopausal for at least one year or surgically sterile). Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence) starting at Screening and continuing through the duration of their study participation.
• The index ulcer has been offloaded with protocol defined offloading device throughout the study run-in period for at least 14 days prior to randomization (Run- in period defined as Screening through TV1/Randomization).
• The index ulcer has a clean base and is free of necrotic debris at time of placement of treatment product.

Exclusion criteria

• Subject has a known life expectancy of < 1 year.
• Index ulcer has been present for >1 year.
• Patient does not have adequate 2-week historical data demonstrating < 25% area reduction.
• Subject is unable to comply with offloading device.
• Presence of any condition(s) which seriously compromises the subject's ability to complete this study or has a known history of poor adherence to medical treatment.
• Subject has ulcers that are completely necrotic or fibrotic tissue.
• Subject has major uncontrolled medical disorders such as serious cardiovascular, renal, liver or pulmonary disease, lupus, palliative care or sickle cell anemia.
• Subject currently being treated for an active malignant disease or subjects with history of malignancy within the ulcer.
• The Subject has other concurrent conditions that in the opinion of the Principal Investigator may compromise subject safety.
• Known contraindications to acellular dermal matrices or known allergies to any of the Miro3D components.
• Concurrent participation in another clinical trial that involves an investigational drug or device that would interfere with this study.
• Index ulcer has reduced in area by ≥25% after 2 weeks of standard of care from the first screening visit (S1) to the TV1/randomization visit.
• Subject is pregnant or breastfeeding.
• Subjects with a history of more than two weeks treatment with immunosuppressants (including systemic corticosteroids >10mg daily dose), cytotoxic chemotherapy, or application of topical steroids to the ulcer surface within 30 days prior to randomization visit or who receive such medications during the screening period, or who are anticipated to require such medications during the course of the study.
• Index ulcer has been previously treated with tissue engineered materials (e.g. Apligraf® or Dermagraft®) or other scaffold materials (e.g. Oasis, Matristem) including any other CAMP within the last 30 days preceding the first treatment visit.
• Affected extremity requiring hyperbaric oxygen during the trial or within 2 weeks of screening visit 1.
• Presence of diabetes with poor metabolic control as documented with an HbA1c ≥12.0 within 30 days of randomization (TV1).
• Index ulcer and/or index limb with presence of gangrene or unstable ischemia at screening (SV1).
• Revascularization surgery on the lower extremity on which the index ulcer is located within 30 days of Screening Visit (SV1).
• Index ulcer in the opinion of the Principal Investigator, is suspicious for cancer and should undergo an ulcer biopsy to rule out a neoplasm of the ulcer.
• Any clinically significant finding, in the judgment of the Principal Investigator, that would place the subject at health risk, impact the study, or affect the completion of the study.