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Multi-Center, Prospective, Randomized Controlled Trial Evaluating SkinTE® in the Treatment of Wagner 2 DFUs (COVER DFUs)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05372809
Recruitment Status : Recruiting
First Posted : May 13, 2022
Last Update Posted : May 13, 2022
Alira Health
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to assess the safety and efficacy of SkinTE for treatment of Wagner grade 2 diabetic foot ulcers.

Condition or disease Intervention/treatment Phase
Diabetic Foot Biological: SkinTE Other: Control Phase 3

Detailed Description:
This study is a prospective, multi-center, randomized controlled trial (RCT) designed to assess the safety and efficacy of SkinTE with standard of care (SOC) dressings compared to SOC dressings alone (wound debridement, collagen-alginate dressing, multi-layer compression dressings, and offloading) in the treatment of Wagner grade 2 diabetic foot ulcers (DFUs) ranging in size from 1 to 10 cm2. After being informed about the study and potential risks, all patients giving written informed consent who meet eligibility criteria will undergo a 2-week screening period of SOC. Patients meeting eligibility criteria following the screening period will be randomized in a single-blind manner (blinded evaluator with closure confirmed by a blinded adjudicator) in a 1:1 ratio to SkinTE with SOC or SOC alone. Patients will be followed weekly for 6 months for wound closure.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: mult-center, randomized controlled trial
Masking: Single (Outcomes Assessor)
Masking Description: Due to the nature of the test article, a placebo harvest procedure or placebo treatment is not possible. Patients will be treated by an unblinded investigator. Wounds will be assessed at each visit by a blinded assessor. Wound closure determined by the blinded assessor will be confirmed by a blinded adjudicator.
Primary Purpose: Treatment
Official Title: Closure Obtained With Vascularized Epithelial Regeneration for DFUs With SkinTE®
Actual Study Start Date : April 28, 2022
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: SkinTE
SkinTE plus standard care
Biological: SkinTE
SkinTE is an Autologous Heterogeneous Skin Construct (AHSC), which is manufactured from a small piece of healthy full-thickness skin harvested from the patient at the time of randomization to the SkinTE arm. SkinTE is manufactured aseptically by PolarityTE following current Good Manufacturing Practice (cGMP). SkinTE is not cultured ex vivo; rather, it is returned to the provider expeditiously to maintain cellular viability. SkinTE includes various multicellular segments as a result of the manufacturing process. The different multicellular segments contain different types of skin cells, such as keratinocytes, dermal fibroblasts, dermal endothelial cells, and follicular cells, as well as extracellular matrix. The multicellular segments have a surface area-to-volume ratio for improved sustenance by imbibition prior to engraftment.
Other Name: Autologous Heterogeneous Skin Construct

Standard care alone
Other: Control

Standard care is defined in this protocol to include the following:

  • Debridement
  • Collagen-alginate primary wound dressing
  • Local offloading with felt pad for wounds on weight bearing surfaces
  • Silicone backed absorbent foam
  • Multi-layer compression dressing
  • Off-loading device such as a full-length boot or total contact cast (if full-length boot cannot accommodate the patient) or surgical shoe for ulcers in non-weight bearing locations
Other Name: Standard of Care

Primary Outcome Measures :
  1. Incidence of index ulcers closed [ Time Frame: 24 weeks ]
    Wound closure is confirmed at two consecutive visits each two weeks apart

Secondary Outcome Measures :
  1. Percent area reduction (PAR) [ Time Frame: Assessed at 4, 8, 12, 16, and 24 weeks ]
    Change in wound area from the time of randomization

  2. Wound Quality of Life (w-QoL) Questionnaire [ Time Frame: 24 weeks ]
    Change in w-QoL from baseline

  3. Wound infection [ Time Frame: 24 weeks ]
    Incidence of new onset infection of index ulcer requiring treatment with antibiotics

Other Outcome Measures:
  1. Incidence of pain, infection, and complications of the harvest site [ Time Frame: 24 weeks ]
  2. Incidence of adverse events of the index ulcer [ Time Frame: 24 weeks ]
  3. Time to closure [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • At least 18 years of age.
  • Documented history of Type I or Type II Diabetes Mellitus requiring oral and/or insulin replacement therapy.
  • Presence of a DFU Wagner 2 grade wound on any aspect of the foot, provided it is at or below the aspect of the medial malleolus. 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.
  • If other wounds are present on the same foot, they must be more than 2 cm distant from the index ulcer.
  • Index ulcer (i.e. current episode of ulceration) has been present for greater than four weeks prior to the initial screening visit (SV1).
  • Index ulcer (post-debridement) is a minimum of 1.0 cm2 and a maximum of 10 cm2 at the first screening visit (SV1) and first treatment visit (RV1).
  • Adequate circulation to the affected foot as documented by a dorsal transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg, or an Ankle Branchial Index (ABI) of ≥ 0.7 and ≤ 1.2 or Arterial Doppler with a minimum of biphasic flow or Toe Brachial Index (TBI) ≥ 0.75 at SV1, using the affected study extremity.
  • 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 PEDIS Grade level 1.
  • The index ulcer has been offloaded with protocol defined offloading device throughout the study screening period for at least 14 days prior to randomization (SV1 through the first randomization visit (RV1)).
  • Negative pregnancy test for females of childbearing potential (e.g., not post- menopausal for at least one year or surgically sterile).
  • Subject understands and is willing to participate in the clinical study and can comply with weekly visits and the follow-up regimen.
  • Females of childbearing potential must agree to use effective methods of contraception (birth control pills, barriers, or abstinence) from screening through end of study (EOS) and undergo pregnancy tests.
  • Properly obtained written informed consent.
  • Subject must have stable living environment in order to manage offloading and wound care management.
  • The index ulcer has a clean base and is free of necrotic debris at time of placement of treatment product.

Exclusion Criteria:

  • 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 (SV1).
  • Index ulcer in the opinion of the investigator is suspicious for cancer and should undergo an ulcer biopsy to rule out a neoplasm of the ulcer.
  • Subjects with history of radiation on the same limb as the index ulcer (regardless of time since last radiation treatment).
  • Subjects with exposed internal fixation on the same limb as the index ulcer (note: external fixation is allowed if deemed stable by the investigator).
  • Subjects on any investigational drug(s) or therapeutic device(s) within 30 days preceding the first screening visit (SV1).
  • Index ulcer treated within the last 30 days prior to screening with a prohibited treatment as defined in full protocol.
  • Subjects with a history of more than two weeks treatment with immunosuppressants (including systemic corticosteroids > 10mg prednisone (or equivalent) daily dose), cytotoxic chemotherapy, or application of topical steroids to the index ulcer surface within one month prior to first screening visit, or who receive such medications during the screening period, or who are anticipated to require such medications during the study.
  • 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.
  • In the opinion of the investigator, the subject is non-compliant with offloading or index ulcer dressing prior to randomization.
  • Active Charcot's arthropathy of the index ulcer limb as verified by clinical evaluation, and/or imaging (x-ray or MRI) within 30 days prior to randomization.
  • Subjects with chronic osteomyelitis and/or cellulitis on the same limb as the index ulcer as verified by clinical evaluation, and/or imaging (x-ray or MRI) within 30 days prior to randomization.
  • Subject is pregnant or breast-feeding.
  • Presence of diabetes with poor metabolic control as documented with an HbA1c ≥12.0 within 30 days of randomization (RV1).
  • Subjects with end stage renal disease as evidenced by an eGFR <30 mL/min/1.73m2 within 120 days of randomization.
  • Index ulcer has reduced or increased in area by 30% or more after 14 days of SOC from SV1 to the RV1/randomization visit.
  • Evidence of unstable human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C in the opinion of the investigator at first screening visit (SV1).
  • Documented history of New York Heart Association Class III or IV congestive heart failure or unstable cardiovascular disease requiring intervention within 60 days prior to screening.
  • Requiring surgical intervention (excluding debridement) at the time of consenting and/or increased probability of requiring surgical intervention during study participation (note: non-invasive surgical intervention is allowed if, per the Principal Investigator, treatment will not affect subject's ability to participate in clinical trial).
  • Any clinically significant finding, in the judgment of the investigator, that would place the subject at health risk, impact the study, or affect the completion of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05372809

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Contact: Ashlee Fishleigh 800-653-8031

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United States, Ohio
NOMS Ankle and Foot Care Centers Recruiting
Youngstown, Ohio, United States, 44512
Contact: Lawrence Didomenico, DPM         
United States, Texas
University of Texas Southwestern Wound Care Clinic Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Lawrence Lavery, DPM, MPH         
Sponsors and Collaborators
Alira Health
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Study Director: Nikolai Sopko, MD, PhD PolarityTE
Study Chair: David Armstrong, DPM, MD, PhD University of Southern California
Principal Investigator: Lawrence Lavery, DPM University of Texas
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Responsible Party: PolarityTE Identifier: NCT05372809    
Other Study ID Numbers: COVER DFUs
First Posted: May 13, 2022    Key Record Dates
Last Update Posted: May 13, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PolarityTE:
diabetic foot ulcer
regenerative medicine
skin regeneration
chronic wounds
Wagner 2
Additional relevant MeSH terms:
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Diabetic Foot
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Foot Ulcer
Leg Ulcer
Skin Ulcer
Skin Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Diabetic Neuropathies