SkinTE® for the Treatment of Wagner 1 Diabetic Foot Ulcers (COVER DFUS II)

NCT06140303 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: COVER DFUs II
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 23

Brief Summary

The purpose of this study is to assess the safety and efficacy of SkinTE for treatment of Wagner grade 1 diabetic foot ulcers.

Conditions

Diabetic Foot

Keywords

diabetic foot ulcer; regenerative medicine; SkinTE; skin regeneration; chronic wounds; Wagner 1

Outcome Measures

Primary Outcomes (1)

• Incidence of index ulcers closed

  Wound closure is confirmed at two consecutive visits each two weeks apart

  12 weeks

Secondary Outcomes (4)

• Percent area reduction (PAR)

  Assessed at 4, 8, and 12 weeks

• Total number of in person wound care clinic visits and/or hospital days related to the index ulcer.

  24 weeks

• Total days of CAM Boot use related to the index ulcer

  24 weeks

• Time to closure

  24 weeks

Study Arms (2)

SkinTE

EXPERIMENTAL

SkinTE plus standard care

Biological: SkinTE

Control

OTHER

Standard care alone

Other: Control

Interventions

SkinTE BIOLOGICAL

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.

Also known as: Autologous Heterogeneous Skin Construct

SkinTE

Control OTHER

Standard care is defined in this protocol to include the following: * Debridement * Collagen dressing * Local offloading * Foam * Multi-layer compression dressing * Off-loading device such as a controlled ankle motion (CAM) boot

Also known as: Standard of Care

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1 grade wound on any aspect of the foot, provided that if the malleolus is involved, not more than 50% of the wound is above the mid-point of the medial malleolus. \[NOTE: DFU must maintain Wagner 1 Grade for the duration of study run-in period - i.e., screening visit 1 (SV1) to randomization visit 1 (RV1).\]
• If other wounds are present on the same foot, they must be more than 2 cm distant from the index ulcer. \[NOTE: If two or more DFUs are present with the same grade, the index ulcer is the largest ulcer and the only one evaluated in the study.\]
• Index ulcer (i.e., current episode of ulceration) has been present for ≥ four weeks (≥28 days) prior to the initial screening visit (SV1).
• Index ulcer (post-debridement) is a minimum of 1.0 cm2 and a maximum of 15 cm2 at first screening visit (SV1) and first randomization 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, using the affected study extremity within 30 days of screening visit (SV1).
• Index ulcer and/or index ulcer limb may have had prior infection(s), 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 study run-in period for at least 14 days prior to randomization (Run-in period defined as Screening through RV1/Randomization).
• 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 study visits and the follow-up regimen.
• Females of childbearing potential must agree to use effective methods of c contraception (birth control pills, barriers, or abstinence) (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, free of necrotic debris, and infection at time of placement of treatment product.

You may not qualify if:

• 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 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 \[NOTE: External fixation is allowed if deemed stable by principal investigator.\]
• Subjects on any investigational drug(s) or therapeutic device(s) within 30 days preceding the first screening visit (SV1). \[NOTE: NPWT is allowed up to the day of screening (SV1), if in the opinion of the Principal Investigator NPWT may be discontinued.\]
• 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 30 days prior to first screening visit (SV1), or who receive such medications during the run-in 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 during the run-in period.
• 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 (RV1).
• 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 (RV1).
• Subject is pregnant or breast-feeding.
• Presence of diabetes with poor metabolic control as documented with an HbA1c ≥12.0 within 30 days prior to randomization (RV1).
• Subjects with end stage renal disease requiring treatment with dialysis and/or evident by an eGFR \<30 mL/min/1.73m2 within 120 days of randomization (RV1). \[NOTE: Subjects with two documented eGFR values within 120 days, the most recent value may be used if the eGFR ≥30 mL/min/1.73m2 and is, in the opinion of the principal investigator, stable and the subject will not require treatment with dialysis for the duration of study participation.\]

Sponsors & Collaborators

• PolarityTE: lead
• Professional Education and Research Institute: collaborator

Study Sites (23)

Titan Clinical Research

Mesa, Arizona, 85202, United States

Location

Center for Clinical Research

Castro Valley, California, 94546, United States

Location

Limb Preservation Platform, Inc.

Fresno, California, 93710, United States

Location

Angel City Research

Los Angeles, California, 90010, United States

Location

Clemente Clinical Research Inc.

Los Angeles, California, 92704, United States

Location

Center for Clinical Research

San Francisco, California, 94115, United States

Location

Clemente Clinical Research Inc.

Santa Ana, California, 92704, United States

Location

ILD Research

Vista, California, 92081, United States

Location

Las Mercedes Medical Research, Inc.

Hialeah, Florida, 33010, United States

Location

Doctors Research Network

Miami, Florida, 33156, United States

Location

DMI Research

Pinellas Park, Florida, 33782, United States

Location

Barry University Clinical Research

Tamarac, Florida, 33321, United States

Location

FASMA - Hagerstown

Hagerstown, Maryland, 21742, United States

Location

Viable Research Management

Henderson, Nevada, 89014, United States

Location

Northwell Health, Inc.

New Hyde Park, New York, 11042, United States

Location

Mount Sinai West Hospital

New York, New York, 10019, United States

Location

LEIRT (Lower Extremity Institute for Research and Therapy)

Boardman, Ohio, 44512, United States

Location

Cutting Edge Research LLC

Circleville, Ohio, 43123, United States

Location

LEIRT (Lower Extremity Institute for Research and Therapy)

East Liverpool, Ohio, 43920, United States

Location

Cutting Edge Research LLC

Grove City, Ohio, 43123, United States

Location

Perfizien Clinical Research LLC.

Houston, Texas, 77055, United States

Location

Baylor Scott & White Health

Plano, Texas, 75093, United States

Location

Foot and Ankle Specialists of the Mid-Atlantic

Salem, Virginia, 24153, United States

Location

MeSH Terms

Conditions

Diabetic Foot

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nikolai Sopko, MD, PhD

  PolarityBio

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the test article, a placebo harvest procedure or placebo treatment is not possible. Patients will be treated by the investigator. Wounds will be assessed at each visit by the investigator. Wound closure determined by the investigator will be confirmed by 3 blinded adjudicators.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: multi-center, randomized controlled trial

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: November 18, 2023
• Study Start: February 22, 2024
• Primary Completion: December 31, 2025
• Study Completion: March 31, 2026
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

US (23)