Miro3D Wound Matrix Study for Diabetic Foot Ulcers and Wound Healing

This study is a prospective, randomized controlled trial designed to evaluate the effectiveness of Miro3D Wound Matrix plus Standard of Care (SOC) compared to SOC alone in treating Wagner Grade 1 diabetic foot ulcers (DFUs) and wound dehiscence in an outpatient setting. The trial is sponsored by Reprise Biomedical, Inc. and aims to explore whether the addition of Miro3D-a three-dimensional, acellular porcine-derived wound matrix-enhances wound healing outcomes compared to SOC alone.

Purpose of the Study: The primary purpose of the study is to determine whether applying Miro3D in combination with SOC leads to improved healing of diabetic foot ulcers compared to SOC alone. Specifically, the study seeks to assess early wound healing progress at four weeks (as measured by percent area reduction and granulation tissue formation) as a predictor of complete healing by twelve weeks.

Key Question the Study Seeks to Answer: Does the addition of Miro3D to standard wound care improve the healing rate and overall wound outcomes for patients with Wagner Grade 1 diabetic foot ulcers or dehisced wounds compared to standard care alone?

Study Design Overview: Subjects who meet inclusion/exclusion criteria will be randomized into one of two groups:

1. Miro3D + SOC arm - receiving Miro3D weekly for 4 weeks, then biweekly if needed, for up to 12 weeks.
2. SOC alone (control) arm - receiving SOC without Miro3D. If the wound remains unhealed at 12 weeks in the SOC alone arm, participants may "crossover" to receive Miro3D treatment under the same schedule for an additional 12 weeks.

Primary Endpoint:

1. Percent Area Reduction (PAR) and granulation tissue formation at 4 weeks, serving as predictors for wound healing at 12 weeks.

Secondary Endpoints:

1. Quality of Life (QOL) improvements, including pain, mobility, and emotional well-being, assessed using a validated Wound/Ulcer-QOL tool.
2. Pain levels using a Visual Analog Scale (VAS) at each visit.

Population: Approximately 30 adult subjects (15 per arm) with Wagner Grade 1 diabetic foot ulcers or dehisced wounds will be enrolled. Subjects must have adequate blood flow, demonstrate wound size criteria, and commit to offloading and follow-up care.

Follow-Up: Subjects will be followed weekly through the 12-week study period. Healed subjects will undergo confirmation visits at 2 and 4 weeks post-closure. Subjects in the crossover arm will be followed for an additional 12 weeks if their wound was unhealed at the primary endpoint.

Statistical Considerations: Data will be summarized using descriptive statistics, including wound measurements, infection status, and healing rates. Comparative analysis will be conducted between treatment groups and schedules (weekly vs. biweekly Miro3D application). Adverse events (AEs), serious adverse events (SAEs), and device-related events will also be documented.

This study aims to generate clinical evidence supporting the use of Miro3D as a beneficial adjunct to standard wound care in promoting early and complete healing of diabetic foot ulcers.

This prospective, randomized controlled trial evaluates the clinical effectiveness of Reprise Biomedical's Miro3D Wound Matrix in conjunction with standard of care (SOC) compared to SOC alone in treating Wagner Grade 1 diabetic foot ulcers (DFUs) in an outpatient setting. The investigational product, Miro3D, is a porcine liver-derived, acellular, three-dimensional extracellular matrix designed to support healing in complex wound environments by providing a biologically active scaffold that facilitates cell infiltration and tissue remodeling. This study aims to generate robust clinical evidence supporting Miro3D's role as an advanced biologic dressing for early and sustained wound healing in diabetic patients.

Background and Rationale: Diabetic foot ulcers are a common and serious complication of diabetes mellitus, affecting approximately 15-25% of individuals with diabetes over their lifetime. These ulcers are associated with high morbidity, increased healthcare utilization, and significant risk of lower extremity amputation. Despite established guidelines, many DFUs fail to heal adequately with standard of care alone, especially when early progress is not observed. According to consensus recommendations, wounds that do not demonstrate at least a 50% reduction in area within the first four weeks of SOC are unlikely to achieve closure by 12 weeks and are considered candidates for advanced wound therapies.

Advanced biologic matrices aim to address the limitations of SOC by enhancing the local wound environment. Miro3D is a perfusion-decellularized extracellular matrix derived from porcine liver, preserving native microvascular architecture and providing a highly porous scaffold for cellular infiltration. Unlike many sheet-based dermal matrices, Miro3D possesses significant three-dimensional structure and volume, making it suitable for filling shallow to moderately deep wound beds. The device is supplied sterile and dry, rehydrated at the point of care, trimmed to fit, and applied directly to the wound bed.

This study is designed to evaluate whether the addition of Miro3D to SOC accelerates healing and improves outcomes in Wagner Grade 1 DFUs, a common clinical presentation that often remains refractory to SOC alone. The trial also includes a crossover design for non-responders in the SOC arm, enhancing ethical treatment access while generating additional observational data.

Device Description and Mechanism of Action: Miro3D Wound Matrix is a sterile, acellular scaffold composed of porcine-derived extracellular matrix processed via perfusion decellularization to retain native liver architecture. The matrix is characterized by high porosity, preserved vascular pathways, and structural integrity, supporting rapid integration into the wound bed. Once rehydrated, Miro3D becomes pliable and conformable, suitable for application to irregular wound geometries.

Mechanistically, Miro3D provides a physical and biochemical scaffold that promotes cell adhesion, migration, angiogenesis, and granulation. As a non-crosslinked, resorbable collagen matrix, it undergoes host remodeling over time, integrating into newly formed tissue. The device can be trimmed to wound dimensions and applied weekly or biweekly depending on healing progression.

Study Objectives and Hypothesis: The primary objective of the study is to determine whether the application of Miro3D in combination with SOC leads to superior healing outcomes compared to SOC alone in the treatment of Wagner Grade 1 DFUs.

Primary Hypothesis: Miro3D + SOC will result in a significantly higher proportion of wounds achieving ≥50% area reduction and robust granulation tissue formation at 4 weeks, predictive of complete closure by 12 weeks.

Secondary Hypotheses: Subjects treated with Miro3D + SOC will demonstrate faster time to healing, improved patient-reported quality of life (QOL), reduced pain, and comparable or improved safety compared to those receiving SOC alone.

Study Design and Randomization: This is a randomized controlled trial enrolling approximately 30 subjects (15 per arm). Subjects meeting eligibility criteria will be randomized in a 1:1 ratio to either:

1. Intervention Arm (Miro3D + SOC): Weekly Miro3D application for the first four weeks, followed by biweekly application if the wound remains unhealed, for up to 12 weeks.
2. Control Arm (SOC alone): Standard wound care practices without Miro3D. Subjects with unhealed wounds at 12 weeks are eligible to cross over to receive Miro3D under the same application schedule for an additional 12-week observational phase.

Randomization will use sealed envelope assignment to ensure unbiased group assignment.

Visit Schedule and Study Assessments:

1. Screening Visit (Week -2 to 0):

   * Informed consent
   * Wound debridement and imaging
   * Vascular assessment
   * HbA1c testing, pregnancy test if applicable
   * Run-in period
2. Randomization Visit (Week 0):

   * Confirm eligibility
   * Randomization
   * Baseline wound measurements and photos
   * QOL and pain scale assessments
   * First application of Miro3D (intervention arm)
3. Weekly Treatment Visits (Weeks 1-11):

   * Wound imaging and measurements
   * Clinical assessment and re-debridement as needed
   * Miro3D reapplication (as indicated)
   * Pain assessment and adverse event tracking
4. End-of-Treatment Visit (Week 12):

   * Final wound assessment
   * Confirmation of wound closure
   * Final QOL and pain scale assessments
   * Eligibility for crossover (control arm, if unhealed)
5. Crossover Phase (Weeks 13-24, as needed):

   * Subjects from SOC arm receive Miro3D + SOC
   * Follow-up per the intervention arm protocol
6. Closure Confirmation Visits (2 and 4 weeks post-closure):

   * Validation of sustained healing

Crossover Design and Follow-Up: Subjects in the SOC arm who do not achieve complete healing by Week 12 are eligible to cross over to receive Miro3D under the same application schedule. The crossover phase is observational and not included in the primary efficacy analysis. These data will help characterize Miro3D's performance as a rescue therapy in chronic wounds unresponsive to SOC.

Subjects who achieve healing during the randomized phase or crossover phase will undergo 2- and 4-week confirmation visits to validate sustained closure.

Safety Monitoring and Adverse Event Reporting: All adverse events will be documented, assessed for severity and relatedness, and reported per FDA and IRB requirements. Investigators will monitor subjects for infection, delayed healing, inflammatory reactions, and systemic complications. Device-related events will be tracked by lot number.

Unanticipated adverse device effects (UADEs), if any, will be escalated to the sponsor and appropriate regulatory bodies. Based on previous clinical use of hepatic-derived ECM scaffolds, Miro3D is expected to demonstrate a favorable safety profile.

Regulatory, Ethical, and Clinical Context: Miro3D Wound Matrix is FDA-cleared under 510(k) as a Class II medical device (K223257) for use in managing partial- and full-thickness wounds. This trial is conducted as a post-market, investigator-initiated study in accordance with Good Clinical Practice (GCP), IRB approval, and informed consent regulations under 21 CFR Part 50.

The trial addresses a critical gap in clinical evidence by comparing Miro3D to SOC in a randomized, controlled framework. Few biologic wound matrices have RCT-level data supporting early use in Wagner Grade 1 DFUs. The findings will inform clinical guidelines, payer coverage decisions, and the design of larger-scale trials aimed at improving outcomes for patients with chronic diabetic wounds.

Eligibility Criteria:
Inclusion Criteria:

1. Must be at least 18 years of age and capable of providing informed consent.
2. Must have a full- or partial-thickness Wagner Grade 1 ulcer or wound on the foot; if involving the malleolus, no more than 50% of the wound may be above the midpoint of the medial malleolus.
3. Index wound/ulcer must be between 1 cm² and 20 cm² post-debridement.
4. Wound/ulcer must have been present for at least 4 weeks prior to screening.
5. Adequate circulation must be documented by one of the following: ABI between 0.7-1.2, TBI ≥ 0.7, TCPO2 ≥ 40 mmHg, or triphasic/biphasic Doppler waveforms.
6. Other wounds, if present, must be at least 2 cm from the index wound/ulcer.
7. Any previous infections must have been adequately treated per IDSA guidelines.
8. Subjects must agree to proper offloading and/or compression, have a stable living environment, and be able to attend follow-up visits.
9. Must provide written consent for digital imaging.
10. For Miro3D arm: Index wound/ulcer must have a clean base free of devitalized tissue or debris at the time of product placement.

Exclusion Criteria:

1. Index wound/ulcer has reduced ≥30% after two weeks of SOC from screening to baseline.
2. Poorly controlled diabetes (HbA1c ≥ 12%).
3. Active, untreated or uncontrolled osteomyelitis.
4. Malignancy or vasculitis at the wound site.
5. Undergoing chemotherapy.
6. On dialysis.
7. Use of investigational drugs or therapies within 30 days prior to screening.
8. Conditions that would compromise study participation or adherence.
9. Known sensitivity to porcine materials.
10. Third-degree burns.
11. Worsening ischemia or gangrene at screening.
12. History of radiation to the wound site.
13. Exposed internal fixation, implants, or hardware in the wound.
14. Patient is transitioning to palliative or comfort care.