Assessment of Wound Closure Comparing Synthetic Hybrid-Scale Fiber Matrix With Standard of Care in Treating Diabetic Foot Ulcers (DFU) and With Living Cellular Skin Substitute in Treating Venous Leg Ulcers (VLU)

Study Overview
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Brief Summary
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In participants with diabetic foot ulcers (DFUs), this study will assess complete wound closure by comparing synthetic hybrid-scale fiber matrix (Restrata®) with standard of care. In participants with venous leg ulcers (VLUs), this study will assess complete wound closure by comparing synthetic hybrid-scale fiber matrix (Restrata®) with living cellular skin substitute (Apligraf®)

Official Title
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Assessment of Wound Closure Comparing Synthetic Hybrid-Scale Fiber Matrix With Standard of Care in Treating Diabetic Foot Ulcers (DFU) and With Living Cellular Skin Substitute in Treating Venous Leg Ulcers (VLU)

Conditions
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Diabetic Foot Ulcer, Venous Leg Ulcer

Intervention / Treatment
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* Device: Synthetic Hybrid-Scale Fiber Matrix
* Device: Standard of Care
* Device: Living Cellular Skin Substitute


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Participants with Diabetic Foot Ulcers: Participant is at least 18 years old Participant is willing and capable of complying with all protocol requirements Participant or legally authorized representative (LAR) is willing to provide written informed consent Participant has Type 1 or Type 2 diabetes (criteria for the diagnosis of diabetes mellitus per American Diabetes Association) Ulcer(s) must be located at least in part on the foot or ankle Ulcer(s) must be present for more than 28 days prior to randomization and initial application of study product, and has not adequately responded to conventional ulcer therapy Wound size must be >1.0 cm^2 and < 25 cm^2 on the day of randomization and initial application of the study product, after initial debridement Participant has adequate circulation to the affected extremity(ies), as demonstrated by at least ONE of the following within 60 days prior to enrollment/randomization: Dorsum transcutaneous oxygen test (TcPO2) of study leg(s) with results ≥40mmHg, OR Ankle-Brachial Index (ABI) of study leg(s) with results of ≥ 0.7 and ≤ 1.3, OR Toe-Brachial Index (TBI) of study extremity(ies) with results of ≥ 0.5 Exclusion Criteria for Participants with Diabetic Foot Ulcers: Participant has been previously enrolled into this study, or is currently participating in another prospective drug or device study that has not reached its primary endpoint Participant is pregnant, breast feeding or planning to become pregnant Participant has a known allergy to resorbable suture materials, e.g. Polyglactin 910 (PGLA), Polydioxanone (PDS) Participant has a life expectancy less than six months as assessed by the investigator Participant has received skin substitutes during the screening period or within 14 days prior to beginning of screening period Participant has an additional wound within 3 cm of the study wound(s) or study wounds are less than 3 cm apart Hgb A1c > 12 percent within 3 months prior to randomization Participant not in reasonable metabolic control in the judgment of the investigator Participant with a known history of poor compliance with medical treatments Participant currently undergoing cancer treatment Participant has been diagnosed with at least one of the following autoimmune connective tissue diseases: lupus, vasculitis, sickle cell, or uncontrolled rheumatoid arthritis Participant is taking parenteral corticosteroids or any cytotoxic agents for 7 consecutive days during the screening period or up to 30 days before the screening period. Chronic oral steroid use is not excluded if dose is < 10 mg per day for prednisone. Active infection, undrained abscess, or critical colonization of the wound(s) with bacteria in the judgment of the investigator Osteomyelitis or exposed bone, probes to bone or joint capsule on investigator's exam or radiographic evidence Participant unwilling or unable to safely utilize appropriate offloading device to unweight wound(s) Study ulcer(s) experiences greater than 30 percent reduction over the 2-week screening period Participant also has a venous leg ulcer that is enrolled into this study Inclusion Criteria for Participants with Venous Leg Ulcers: Participant is at least 18 years old Participant is willing and capable of complying with all protocol requirements Participant or legally authorized representative (LAR) is willing to provide written informed consent Participant has peripheral venous disease per investigator judgment or diagnostic confirmation Ulcer(s) must be venous in origin, located on a lower extremity Ulcer(s) must be present for more than 28 days prior to randomization and initial application of study product, and has not adequately responded to conventional ulcer therapy Wound(s) size must be >1.0 cm^2 and < 50 cm^2 on the day of randomization and initial application of the study product, after initial debridement Participant has adequate circulation to the affected extremity(ies), as demonstrated by at least ONE of the following within 60 days prior to enrollment/randomization: Dorsum transcutaneous oxygen test (TcPO2) of study leg(s) with results ≥ 40mmHg, OR Ankle-brachial index (ABI) of study leg(s) with results of ≥ 0.7 and ≤ 1.52, OR Toe-Brachial Index (TBI) of study leg(s) with results of ≥ 0.5, OR Doppler arterial waveforms, which are triphasic or biphasic at the ankle of the affected leg(s) Exclusion Criteria for Participants with Venous Leg Ulcers: Participant has been previously enrolled into this study, or is currently participating in another prospective drug or device study that has not reached its primary endpoint Participant is pregnant, breast feeding or planning to become pregnant Participant has a known allergy to resorbable suture materials, e.g. Polyglactin 910 (PGLA), Polydioxanone (PDS) Participant has a known allergy to bovine materials or agarose shipping materials Participant has a life expectancy less than six months as assessed by the investigator Participant has received skin substitutes during the screening period or within 14 days prior to the beginning of the screening period Participant has an additional wound within 3 cm of the study wound or study wounds are less than 3 cm apart Hgb A1c > 12 percent within 3 months prior to randomization in patients with a known history of diabetes Participant is not in reasonable metabolic control in the judgment of the investigator Participant has a known history of poor compliance with medical treatments Participant currently undergoing cancer treatment Participant has been diagnosed with at least one of the following autoimmune connective tissue diseases: lupus, vasculitis, sickle cell, or uncontrolled rheumatoid arthritis Participant is taking parenteral corticosteroids or any cytotoxic agents for 7 consecutive days during the screening period or up to 30 days before the screening period. Chronic oral steroid use is not excluded if dose is < 10 mg per day for prednisone. Active infection, undrained abscess, or critical colonization of the wound(s) with bacteria in the judgment of the investigator Participant unwilling or unable to tolerate use of compression therapy for the duration of the study Study ulcer(s) experiences greater than 30 percent reduction over the 2-week run-in period Participant also has a diabetic foot ulcer that is enrolled into this 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diabetic Foot Ulcer Participants Assigned to Synthetic Hybrid-Scale Fiber Matrix (Restrata®)<br>Biweekly (every 2 weeks) application for either 12 weeks or until 100 percent epithelialization / wound closure (whichever occurs first) | Device: Synthetic Hybrid-Scale Fiber Matrix<br>* A synthetic absorbable skin substitute indicated for use in the local management of wounds. It is made of small synthetic fibers that are designed to be similar to the structure of human skin.<br>* Other names: Restrata;|
| Active Comparator: Diabetic Foot Ulcer Participants Assigned to Standard of Care<br>Weekly application for either 12 weeks or until 100 percent epithelialization / wound closure (whichever occurs first) | Device: Standard of Care<br>* To ensure off-loading, each patient will be fitted with an off-loading device based on the investigator's decision, e.g. a boot for forefoot and a heel protector for hindfoot. Patients is instructed on how to care for the surgical site, utilize an off-loading device, and keep the surgical site moist and clean. If the wound is dry, a hydrogel category dressing type should be used. If the wound has exudate, an alginate or foam dressing is recommended.<br>|
| Experimental: Venous Leg Ulcer Participants Assigned to Synthetic Hybrid-Scale Fiber Matrix (Restrata®)<br>Biweekly (every 2 weeks) application for either 16 weeks or until 100 percent epithelialization / wound closure (whichever occurs first) | Device: Synthetic Hybrid-Scale Fiber Matrix<br>* A synthetic absorbable skin substitute indicated for use in the local management of wounds. It is made of small synthetic fibers that are designed to be similar to the structure of human skin.<br>* Other names: Restrata;|
| Active Comparator: Venous Leg Ulcer Participants Assigned to Living Cellular Skin Substitute (Apligraf®)<br>Biweekly (every 2 weeks) application for either 16 weeks or until 100 percent epithelialization / wound closure (whichever occurs first) | Device: Living Cellular Skin Substitute<br>* An absorbable skin substitute comprised of human and bovine (cow) tissues indicated for use in the local management of wounds.<br>* Other names: Apligraf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For Participants With Diabetic Foot Ulcers, number of participants with 100 Percent Epithelialization (Closure) of Wound | 100 percent epithelialization of wound as assessed by a blinded evaluator via review of a three-dimensional high resolution photo of the wound plus confirmation of no drainage or need for additional dressing 2 weeks after 100 percent epithelialization | 12 weeks | 
| For Participants With Venous Leg Ulcers, number of participants with 100 Percent Epithelialization (Closure) of Wound | 100 percent epithelialization of wound as assessed by a blinded evaluator via review of a three-dimensional high resolution photo of the wound plus confirmation of no drainage or need for additional dressing 2 weeks after 100 percent epithelialization | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in Wound Area | Wound area measurements will be made via a three-dimensional high resolution photo of the wound with automated measurements. | Weekly assessments for 12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first. | 
| Time to 100 Percent Epithelialization | The number of weeks from initial application of study product until 100 percent epithelialization is first identified. | 12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first. | 
| Number of Product Applications | The number of applications of study product until 100 percent epithelialization is first identified | 12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first |