DFC 004 Biomarkers for Active Diabetic Foot Ulcers

Study Overview
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Brief Summary
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This study is a platform study designed to efficiently test multiple biomarkers to identify diabetic foot ulcers (DFUs) with a higher potential for healing versus not healing that ultimately could be applied at the point of care to drive personalized management decisions, and to better inform clinical trials of wound healing interventions

Detailed Description
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This study is a platform study designed to efficiently test multiple biomarkers to identify diabetic foot ulcers (DFUs) with a higher potential for healing versus not healing that ultimately could be applied at the point of care to drive personalized management decisions, and to better inform clinical trials of wound healing interventions The platform study is designed to be flexible so that it is suitable for a wide range of studies relevant to patients with open (active) DFUs. This platform study will enroll patients with DFUs seen in an outpatient setting in diabetic foot and wound care clinics across a range of healthcare systems, including community settings and tertiary care hospitals, participating in the DFC. The platform study will include common procedures that are applicable across the entire spectrum of DFUs (e.g., uniform biospecimen collections, clinical and usual care characteristics, social determinants of health, and patient reported outcomes). Blood, wound fluid (by a variety of methods), wound dressings, and debridement tissue (if debridement is performed during the participant's clinical wound care) will be collected from all participants to support a biorepository for concurrent and future research. Urine samples will be collected if participants agree to provide them, and collection will be encouraged. Biomarker-specific studies requiring additional data or biospecimens not required in the platform study will be included as appendices, as needed. Other biomarker-specific studies that use platform study biospecimens and study data will follow the DFC ancillary study process. Eligible participants enrolled in the master protocol who signed the informed consent may be enrolled in multiple biomarkers sub studies associated with the master protocol without the need to sign an additional informed consent. This platform study is non-interventional; no study prescribed agents or therapies are administered. Eligible and consented participants are managed at each DFC site according to the usual clinical care, which is expected to be in line with the current standards of care recommendations1-3. The study will collect relevant details regarding the care provided at each clinic visit and participant outcomes. Follow-up for participants will vary based upon the occurrence and timing of healing: All participants will be followed every other week for one month and monthly thereafter until the wound is healed or week 52 if the wound has not healed. Participants who experience wound healing prior to week 52 will have a confirmation visit 2 weeks later. These participants will also be assessed for recurrence of their DFU at weeks 52 and 78 via phone call or video visit. Participants who experience wound healing at week 52 will have a confirmation visit 2 weeks later. These participants will also be assessed for recurrence of their DFU at week 78 via phone call or video visit. Participants who do not experience wound healing by week 52 will have an additional phone call or video visit scheduled at week 78 to assess patient-reported wound healing, infection, or amputation with confirmation by electronic medical records (EMR), if available. Study visits may occur in conjunction with the participant's scheduled clinical follow-up visits. After wound healing has been confirmed, the visit may be conducted by remote means. The master protocol will enable evaluation of the time to healing over a 78-week period and of expectations on the natural history of wound healing in contemporary DFU participants. It also enables exploring rates of DFU recurrence in those who healed. These data will lead to more accurate DFU-specific standards of care guidelines that will have a direct impact and benefit in the clinical care, for a personalized approach. General and biomarker-specific analyses will be performed. Participants who share common demographic or clinical characteristics may be pooled across substudies.

Official Title
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Predictive and Diagnostic Biomarkers for Diabetic Foot Ulcers: Open Wound Master Study

Conditions
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Diabetic Foot Ulcer, Diabetic Foot, Diabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form. Age 18 years or older. Clinically diagnosed with diabetes or meeting the American Diabetes Association (ADA) criteria. [ADA Standards of Clinical Care Diabetes Care 2022, Suppl 1] Open foot ulcer, defined as an open wound from malleolus down. This includes post-surgical wounds within this area left open to heal by secondary intention. In case of multiple ulcers, the largest ulcer will be considered the study index DFU. Agreement to adhere to protocol visits and provide all required biospecimens and clinical data. Exclusion Criteria: Participation in an interventional clinical trial for DFU within 1 month of Visit 1. Currently receiving radiation to target area or chemotherapy. Gangrene in any portion of the foot with the index ulcer. Planned revascularization or under evaluation for revascularization of the index limb for advanced ischemia within next 4 weeks of Week 0. Severe limb ischemia (SVS WIfl Ischemia grade 3). Any concomitant medical or psychiatric condition that, in the opinion of the investigator(s), would compromise the participant's ability to safely complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Diabetic Foot Ulcer<br>Adult individuals with at least one diabetic foot ulcer who meet inclusion/exclusion criteria | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound Healing | Proportion of participants with complete wound healing by week 52, defined as complete wound closure where there is skin re-epithelialization without drainage or dressing requirements at two consecutive study visits 2 weeks apart. | 52 Weeks | 
| DFU Infections | Proportion of participants who develop infections of the index DFU among those with no infections at baseline. | 52 Weeks | 
| Amputations | Proportion of participants who have an amputation of the limb associated with the index DFU. | 52 Weeks | 
| Prediction Performance | Measures of prediction performance (e.g., predictive power, AUC, ROC, Akaike information criterion) of biomarker(s) for each of the clinical outcomes: Wound Healing, DFU Infections, and Amputations described above. Prediction performance is measured by multiple statistical measures to assess ability of the biomarker to predict event risk for each of the three clinical outcomes. | 52 Weeks | 
| Biospecimens Count | Proportion of eligible participants providing biospecimens by site, and by type (serum, plasma, wound fluid, wound dressings, wound debridement tissue, urine). | 52 Weeks | 
| Biospecimen Quality | Proportion of biospecimens of adequate quality by type. | 52 Weeks | 
| Standard of Care Prescription by Site | Proportion of sites that prescribe the most current SOC into usual care, specifically for: (a) offloading; (b) vascular assessment; and (c) debridement. | 52 Weeks | 
| Standard of Care Adherence | Proportion of participants who adhere to physician-prescribed SOC therapies for their DFU care. | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Healing | Time to healing, defined as the time (in weeks) from baseline to complete healing. | Up to 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in SF-12 Physical Domain Score | Change from baseline to later of Week 52 or Confirmation Visit in: SF-12 physical domain score. SF-12 for physical Score range from 0-100 Higher scores indicate better physical health. | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in SF-12 Mental Domain Score | Change from baseline to later of Week 52 or Confirmation Visit in: SF-12 mental domain score. Score range from 0-100 Higher scores indicate better mental health. | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF subscale leisure score. | Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring Five-point scale: 1=never to 5=all the time Score is based on sum of all items Scored 0-100 - higher scores indicate better QOL | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF physical health subscale score. | Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring Five-point scale: 1=never to 5=all the time Score is based on sum of all items Scored 0-100 - higher scores indicate better QOL | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF dependence/daily life subscale score. | Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring Five-point scale: 1=never to 5=all the time Score is based on sum of all items Scored 0-100 - higher scores indicate better QOL | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF negative emotions subscale score. | Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring Five-point scale: 1=never to 5=all the time Score is based on sum of all items Scored 0-100 - higher scores indicate better QOL | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF worried about ulcers/feet subscale score | Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring Five-point scale: 1=never to 5=all the time Score is based on sum of all items Scored 0-100 - higher scores indicate better QOL | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in DFS-SF bother by ulcer care subscale score. | Change from baseline to later of Week 52 or Confirmation Visit in: DFS-SF subscale scores (leisure, physical health, dependence/daily life, negative emotions, worried about ulcers/feet, bother by ulcer care). DFS-SF subscale scoring Five-point scale: 1=never to 5=all the time Score is based on sum of all items Scored 0-100 - higher scores indicate better QOL | 52 Weeks | 
| Change from baseline to later of Week 52 or Confirmation Visit in PROMIS Sleep Disturbance | Change from baseline to later of Week 52 or Confirmation Visit in: PROMIS Sleep disturbance. Each items has a 5-point response scale 1=never, 2=rarely, 3=sometimes, 4=often, 5=always Score ranges from 8-40; higher scores indicate greater severity of sleep disturbance. | 52 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetic foot ulcer, Diabetic Foot Consortium