Trial to Evaluate the Safety and Effectiveness of Treatment With COMS One Device in Subjects With Diabetic Foot Ulcers

Study Overview
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Brief Summary
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The purpose of this clinical trial is to evaluate the safety and effectiveness of the treatment with the COMS One device in subjects with refractory diabetic foot ulcers (DFUs). The prospective randomized, double-blinded, sham-controlled trial is designed to demonstrate superiority of wound closure of the COMS One device to a sham-control device at 12 weeks post-application, when each is administered in conjunction with standard of care (SOC) in the treatment of DFUs.

Detailed Description
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The purpose of this clinical trial is to evaluate the safety and effectiveness of the treatment with the COMS One device in subjects with refractory diabetic foot ulcers (DFUs). The prospective randomized, double-blinded, sham-controlled trial is designed to demonstrate superiority of wound closure of the COMS One device to a sham-control device at 12 weeks post-application, when each is administered in conjunction with standard of care (SOC) in the treatment of DFUs. Primary Objective The COMS One Therapy System is intended to promote wound healing in chronic DFUs. As part of the clinical investigation, the primary objective is to determine complete wound healing at 12 weeks post-application of the device defined as complete skin re-epithelialization without drainage confirmed by 2 consecutive trial visits 2 weeks apart. Secondary Objectives Secondary objectives are confirmation of safety and assessment of wound healing parameters as well as subject and site reported outcomes. A total of 320 subjects with refractory DFU will be screened. It is expected that 30% of subjects will be excluded from the trial if either of the following occur between screening and randomization: >30% wound closure over a period of 2 weeks or >50% wound closure over a period of 4 weeks (measured post-debridement). The remaining 224 subjects will be randomized into two groups (112 Subjects Sham device treated; 112 Subjects Coms One device treated).

Official Title
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Concurrent Optical and Magnetic Stimulation (COMS) for Treatment of Refractory Diabetic Foot Ulcer; a Prospective Randomized, Sham-controlled, Double-blinded, Pivotal Clinical Trial

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Device: COMS One device
* Device: Sham device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are male or female, ≥22 and ≤90 years of age Female subjects of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence) starting at screening and throughout the duration of their study participation. Able to understand and sign the informed consent form (ICF) and comply with requirements set in the protocol including trial visits, trial treatment and dressing regimens and compliance with required offloading device (if applicable) Type 1 or Type 2 diabetes mellitus Presence of one full-thickness DFU located at or below the malleoli (If the subject has more than one DFU that meets eligibility criteria, the investigator will designate one DFU as the target DFU to be treated in the trial) Wagner Grade 1 or 2 (without bone exposure) There is a minimum 2 cm margin between the target DFU and any other ulcer on that same foot, post-debridement Target DFU duration >30 days and <52 weeks Target DFU area between 0.5 - 25 cm2 at screening (Target DFU is ≥ 0.5cm2 after debridement at start of Run-In Phase) Adequate vascular perfusion of the target limb (same limb as where the target DFU is located) as evidenced by: either a skin perfusion pressure (SPP) measurement of ≥30mmHg OR an ankle-brachial index (ABI) >0.7 but less than 1.2 or a toe-brachial index (TBI) >0.4 but less than 0.7 or a transcutaneous oxygen pressure (TcPO2) >40mmHg Exclusion Criteria: Known pregnancy or lactating Active skin cancer, a history of skin cancer or any other localized cancer, precancerous lesions or large moles in the areas to be treated. Subject who is taking any medications the Principal Investigator (PI) believes may interfere with healing of the target DFU Subject who is currently undergoing treatment for an active systemic infection, including osteomyelitis Wagner Grade 3, 4 or 5 Participation in another trial with investigational drug or device within the 30 days preceding and during the present trial Any co-morbid medical condition which places the subject at unreasonable risks in the opinion of the investigator (such as history of HIV or a clinically significant cardiac, gastrointestinal, endocrine, neurological, liver, or kidney disease) of the investigator) Subject has chronic renal insufficiency requiring dialysis (end stage renal disease) Subject is being treated with systemic corticosteroids (prednisone, dexamethasone, hydrocortisone, methylprednisolone, or similar) >10mg/day for more than 10 days or any dose >30 days For subjects in the 2-Week Run-In Phase: more than 30% closure of target DFU at Screening Run-In Phase Visit I or Randomization/Baseline Visit or more than 50% closure of target DFU between the 2 Week Historical Period and Randomization/Baseline Visit (measured post-debridement) For subjects in the 4-Week Run-In Phase: more than 30% closure of target DFU at Screening Run-In Visit II or between Screening Run-In Phase Visit II and Randomization/Baseline Visit or more than 50% closure of target DFU between Screening Run-In Phase Visit I and Randomization/Baseline Visit (measured post-debridement) Blood chemistry or counts values as follows (based on subject's medical files): Pre-albumin <10 mg/dL Serum BUN >60 mg/dL Serum creatinine >4.0 mg/dL WBC <2.0 x 109/L Hemoglobin <8.0 g/dL Absolute neutrophil <1.0 x 109/L Platelet count <50 x 109/L HbA1C >12%

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 90 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
Interventional Model Description: The purpose of this clinical trial is to evaluate the safety and effectiveness of treatment with the COMS One device in subjects with refractory DFUs. The randomized, sham-controlled, double-blinded trial is designed to demonstrate superiority of wound closure of the COMS One device to a Sham-control device at 12 weeks post-application, when each is administered in conjunction with SOC, in the treatment of DFUs. Following randomization, subjects will be assigned treatment with either COMS One device or the Sham device in conjunction with SOC. At least 50% of subjects are required to be 65 years or older at randomization. Prospective, randomized, double-blinded, placebo-controlled trials provide the most objective methods for analyzing the outcomes of multiple treatment groups. The blinded use of a sham device allows for a true comparison of COMS One treatment in conjunction with SOC to SOC alone.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: COMS One device<br>The COMS One device is reusable (the component can be used on multiple subjects and is cleaned between uses). The COMS One device is the housing unit for the user controls, displays and functions including embedded software, lithium-ion battery, optical (LEDs) and a magnetic stimulation coil. The COMStouch is a sterile single-use component. The COMStouch provides a base and sterile barrier for the COMS One device. The COMSfix component is a self-adhesive single-use strap used to hold the COMS One device and COMStouch components in place during treatment. | Device: COMS One device<br>* The COMS One device incorporates technologies for optical and magnetic stimulation. The optical stimulation component is designed to emit light by two types of light emitting diodes (LEDs) in the wavelength of 660 nm (red) and 830 nm (near infrared) range of the electromagnetic spectra. The magnetic stimulation component is generated by a coil emitting pulse modulated magnetic fields in the extremely low frequency (ELF) range of the electromagnetic spectra. The System is a lightweight, portable device. The device is applied via a single use disposable component (COMStouch) that provides a base and sterile barrier for the unit. The device is attached via a single use strap (COMSfix). The device has been slightly adapted in order to make sure blinding is achieved/maintained. The specific feature that has been modified for the purposes of blinding is sensor detecting whether the device is lying on the skin.<br>* Other names: Concurrent Optical and Magnetic Stimulation;|
| Sham Comparator: Sham device<br>The sham device is reusable (the component can be used on multiple subjects and is cleaned between uses). The sham device is the housing unit for the user controls, displays and functions including embedded software, lithium-ion battery, optical (LEDs) and a magnetic stimulation coil. The COMStouch is a sterile single-use component. The COMStouch provides a base and sterile barrier for the sham device. The COMSfix component is a self-adhesive single-use strap used to hold the sham device and COMStouch components in place during treatment. | Device: Sham device<br>* The Sham device is a lightweight, portable device. The device is applied via a single use disposable component (COMStouch) that provides a base and sterile barrier for the unit. The device is attached via a single use strap (COMSfix). The device has been slightly adapted in order to make sure blinding is achieved/maintained. The specific features that have been modified for the purposes of blinding include the following: 1) therapeutic output, and 2) sensor detecting whether the device is lying on the skin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete wound healing | The primary endpoint for this pivotal trial is complete wound closure after 12 weeks of treatment, which is defined as complete skin re-epithelialization without drainage confirmed by 2 consecutive trial visits 2 weeks apart. | 12 weeks post application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median time to 50% wound area reduction | Time in number of days until wound area is reduced by 50% compared to wound area at time of randomization | 24 weeks | 
| Median time to 90% wound area reduction | Time in number of days until wound area is reduced by 90% compared to wound area at time of randomization | 24 weeks | 
| Incidence of complete wound closure | Incidence of complete wound closure after 8, 16, 20, and 24 weeks, which is defined as complete skin re-epithelialization without drainage | 8 week, 16 week, 20 week and 24 week | 
| Partial wound closure | Percent Wound Area Reduction (PWAR) at week 8, 12, 16, 20, 24 | 8 week, 12 week, 16 week, 20 week and 24 week | 
| Incidence of all related or serious adverse events | Number of subjects with one or more related adverse event or serious adverse events Related adverse events are those judged by the investigator to be possibly, probably, or definitely related to the COMS One device or other trial procedures. | 24 weeks | 
| Time to target diabetic foot ulcer re-occurrence | Time in number of days from randomization until re-occurrence of the target diabetic foot ulcer, assessed up to 24 weeks | Up to 24 weeks | 
| Time to amputation | Time in number of days from randomization until amputation associated with the target diabetic foot ulcer, assessed up to 24 weeks | Up to 24 weeks | 
| Pain assessment | Wong-Baker FACES Pain Rating Scale - patient chooses the face that best demonstrates the physical pain they are experiencing at four time points throughout study participation | Week 1, Week 8, Week 12, Week 24 | 
| Quality of life survey | 36-Item Short Form Survey (SF-36) - health-related quality of life questionnaire that is completed by patients at four time points throughout study participation | Week 1, Week 8, Week 12, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory Diabetic Foot Ulcer (DFU)