Diabetic Foot Ulcer
Conditions
Brief summary
The purpose of this clinical evaluation is to collect patient outcome data on a commercially available 510K FDA cleared advanced skin substitute. The commercially available product is Helicoll® Advanced Skin Substitute. In this trial two groups of subjects with Wagner 1 diabetic foot ulcers (DFUs), will receive standard of care (SOC) treatment for their condition. Half of the patients will have their SOC treatment with Epifix® or Grafix® and the other half will receive a 510K FDA cleared Helicoll® Advanced Skin Substitute as the primary treatment. The primary endpoint is the percentage wound area reduction of the target ulcer. Secondary endpoints include the proportion of subjects that obtain complete closure over the 5-week treatment period, the time to achieve complete wound closure of the target ulcer by the end of 5 weeks, and mean number of IP applications.
Interventions
DEVICESOC and Advanced Bioengineered Skin Substitute
SOC primary dressing with Helicoll®
OTHERSOC and Active Comparator
SOC primary dressing with Epifix® or Grafix®
Sponsors
Encoll Corp
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must be at least 18 years of age or older. 2. Subjects must have a diagnosis of type 1 or 2 Diabetes mellitus. 3. At randomization, subjects must have a target diabetic foot ulcer with a minimum surface area of 1.0 cm2 and a maximum surface area of 10.0 cm2 measured post debridement using a ruler to measure wound area. 4. The target ulcer must have been present for a minimum of 4 weeks and a maximum of 52 weeks of standard of care prior to the initial screening visit. 5. The target ulcer must be located on the foot with at least 50% of the ulcer below the malleolus. 6. The target ulcer must be full thickness on the foot or ankle that does not probe to bone. 7. Adequate circulation to the affected foot as documented by any of the following methods performed within 3 months of the first screening visit: 1. TCOM ≥30 mmHg 2. ABI between 0.7 and 1.3 3. PVR: Biphasic 4. TBI ˃0.6 5. As an alternative, arterial Doppler ultrasound can be performed evaluating for biphasic dorsalis pedis and posterior tibial vessels at the level of the ankle of the target extremity. 8. If the subject has two or more ulcers, they must be separated by at least 2 cm. The largest ulcer satisfying the inclusion and
Exclusion criteria
will be designated as the target ulcer. 9. The subject must consent to using the prescribed off-loading method for the duration of the study. 10. The subject must agree to attend the twice-weekly/weekly study visits required by the protocol. 11. The subject must be willing and able to participate in the informed consent process. 12. Patients must have read and signed the IRB approved ICF before screening procedures are undertaken.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Wound Area Reduction | 4 weeks | Average Percentage of Wound Area Reduction from Treatment Visit 1 to Treatment Visit 4 measured manually with digital photography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Repeated Applications | 4 weeks | Number of Participants with repeated applications of the Advanced Skin Substitute used to obtain wound closure |
| Proportion of Complete Closure | 5 weeks | The proportion of subjects that obtain complete closure over the 5-week treatment period |
| Time to Achieve Complete Wound Closure | 5 weeks | The time to achieve complete wound closure of the target ulcer by the end of 5 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Analysis for Treatment Emergent Adverse Events | 5 weeks | The number and type of Treatment Emergent Adverse Events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SOC and Advanced Bioengineered Skin Substitute The SOC therapy in this study is offloading of the DFU (CAM boots or total contact casting \[TCC\] if the subject's foot is too large for a CAM boot), appropriate sharp or surgical debridement, infection management (systemic antibiotics only in conjunction with debridement) and wound care covering with Helicoll® applied weekly or as needed followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap (Dynaflex™ or equivalent).
SOC and Advanced Bioengineered Skin Substitute: SOC primary dressing with Helicoll® | 12 |
| SOC and Active Comparator The SOC therapy in this study is offloading of the DFU (CAM boots or total contact casting \[TCC\] if the subject's foot is too large for a CAM boot), appropriate sharp or surgical debridement, infection management (systemic antibiotics only in conjunction with debridement) and wound care covering with Epifix® or Grafix® followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap (Dynaflex™ or equivalent).
SOC and Active Comparator: SOC primary dressing with Epifix® or Grafix® | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | SOC and Active Comparator | Total | SOC and Advanced Bioengineered Skin Substitute |
|---|---|---|---|
| Age, Continuous | 61.1 years STANDARD_DEVIATION 12.29 | 60.8 years STANDARD_DEVIATION 12.16 | 60.4 years STANDARD_DEVIATION 12.03 |
| Amputations, Minor 0 | 6 Participants | 15 Participants | 9 Participants |
| Amputations, Minor 1 | 1 Participants | 2 Participants | 1 Participants |
| Amputations, Minor 2 | 5 Participants | 6 Participants | 1 Participants |
| Amputations, Minor 5 | 0 Participants | 1 Participants | 1 Participants |
| Anatomical location Forefoot | 6 Participants | 11 Participants | 5 Participants |
| Anatomical location Heel | 1 Participants | 1 Participants | 0 Participants |
| Anatomical location Midfoot | 1 Participants | 5 Participants | 4 Participants |
| Anatomical location Toe | 4 Participants | 7 Participants | 3 Participants |
| Any psychiatric condition | 3 Participants | 5 Participants | 2 Participants |
| BMI | 29.8 kg/m^2 STANDARD_DEVIATION 10.61 | 31.2 kg/m^2 STANDARD_DEVIATION 7.93 | 32.5 kg/m^2 STANDARD_DEVIATION 5.24 |
| Chronic Heart Failure (CHF) | 0 Participants | 2 Participants | 2 Participants |
| Chronic Kidney Disease (CKD) | 1 Participants | 1 Participants | 0 Participants |
| Comorbidity count | 6.9 Comorbidities STANDARD_DEVIATION 4.06 | 7 Comorbidities STANDARD_DEVIATION 4.06 | 7.1 Comorbidities STANDARD_DEVIATION 4.06 |
| Creatinine | 0.93 mg/dL STANDARD_DEVIATION 0.35 | 1.01 mg/dL STANDARD_DEVIATION 0.3 | 1.08 mg/dL STANDARD_DEVIATION 0.24 |
| DFU position Lateral | 5 Participants | 9 Participants | 4 Participants |
| DFU position Medial | 7 Participants | 15 Participants | 8 Participants |
| Foot deformities Ankle tarsal tunnel | 0 Participants | 1 Participants | 1 Participants |
| Foot deformities Charcot (stable) | 2 Participants | 3 Participants | 1 Participants |
| Foot deformities No deformities | 9 Participants | 19 Participants | 10 Participants |
| Foot deformities Plantar arthrodesis | 1 Participants | 1 Participants | 0 Participants |
| HbA1c | 7.6 Percentage STANDARD_DEVIATION 1.69 | 7.6 Percentage STANDARD_DEVIATION 2.04 | 7.5 Percentage STANDARD_DEVIATION 2.38 |
| History DFU recurrence | 4 Participants | 10 Participants | 6 Participants |
| History offloading type CAM boot | 5 Participants | 12 Participants | 7 Participants |
| History offloading type No offloading | 3 Participants | 4 Participants | 1 Participants |
| History offloading type Surgical shoe | 4 Participants | 8 Participants | 4 Participants |
| Hypertension | 6 Participants | 17 Participants | 11 Participants |
| Leg edema | 0 Participants | 1 Participants | 1 Participants |
| Major amputations | 1 Participants | 1 Participants | 0 Participants |
| Number of sharp debridements | 3.8 Sharp debridements STANDARD_DEVIATION 0.94 | 3.7 Sharp debridements STANDARD_DEVIATION 1.2 | 3.5 Sharp debridements STANDARD_DEVIATION 1.45 |
| Other concurrent DFUs (at screening) 0 | 10 Participants | 19 Participants | 9 Participants |
| Other concurrent DFUs (at screening) 1 | 0 Participants | 2 Participants | 2 Participants |
| Other concurrent DFUs (at screening) 2 | 2 Participants | 3 Participants | 1 Participants |
| Peripheral Arterial Disease/Peripheral Vascular Disease (PAD/PVD) | 0 Participants | 1 Participants | 1 Participants |
| Peripheral neuropathy | 12 Participants | 20 Participants | 8 Participants |
| Prior DFU count | 3.9 Count of Ulcer STANDARD_DEVIATION 8.25 | 3.9 Count of Ulcer STANDARD_DEVIATION 6.56 | 3.8 Count of Ulcer STANDARD_DEVIATION 4.86 |
| Race/Ethnicity, Customized Race/Ethnicity African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian | 12 Participants | 22 Participants | 10 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 12 participants | 24 participants | 12 participants |
| Restricted mobility | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 18 Participants | 8 Participants |
| Smoker Current | 1 Participants | 1 Participants | 0 Participants |
| Smoker Former | 5 Participants | 9 Participants | 4 Participants |
| Smoker Never smoked | 6 Participants | 14 Participants | 8 Participants |
| Venous disease | 0 Participants | 0 Participants | 0 Participants |
| Vertical location Dorsal | 1 Participants | 1 Participants | 0 Participants |
| Vertical location Plantar | 11 Participants | 23 Participants | 12 Participants |
| Wound age | 23.8 Weeks STANDARD_DEVIATION 12.4 | 20.2 Weeks STANDARD_DEVIATION 13.02 | 16.5 Weeks STANDARD_DEVIATION 13.63 |
| Wound area | 2.4 cm2 STANDARD_DEVIATION 1.77 | 2.35 cm2 STANDARD_DEVIATION 1.95 | 2.3 cm2 STANDARD_DEVIATION 2.13 |
| Years of DFUs | 4.9 years STANDARD_DEVIATION 16.45 | 5.4 years STANDARD_DEVIATION 14.72 | 5.9 years STANDARD_DEVIATION 12.98 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Percentage of Wound Area Reduction
Average Percentage of Wound Area Reduction from Treatment Visit 1 to Treatment Visit 4 measured manually with digital photography
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOC and Advanced Bioengineered Skin Substitute | Percentage of Wound Area Reduction | 83.9 Percentage of Wound Area Reduction | Standard Deviation 24.93 |
| SOC and Active Comparator | Percentage of Wound Area Reduction | 71.3 Percentage of Wound Area Reduction | Standard Deviation 36.8 |
Secondary
Number of Participants With Repeated Applications
Number of Participants with repeated applications of the Advanced Skin Substitute used to obtain wound closure
Time frame: 4 weeks
Population: Healed wounds only
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOC and Advanced Bioengineered Skin Substitute | Number of Participants With Repeated Applications | 1 Repeated Application | 1 participants |
| SOC and Advanced Bioengineered Skin Substitute | Number of Participants With Repeated Applications | 2 Repeated Applications | 1 participants |
| SOC and Advanced Bioengineered Skin Substitute | Number of Participants With Repeated Applications | 4 Repeated Applications | 4 participants |
| SOC and Active Comparator | Number of Participants With Repeated Applications | 1 Repeated Application | 0 participants |
| SOC and Active Comparator | Number of Participants With Repeated Applications | 2 Repeated Applications | 1 participants |
| SOC and Active Comparator | Number of Participants With Repeated Applications | 4 Repeated Applications | 2 participants |
Secondary
Proportion of Complete Closure
The proportion of subjects that obtain complete closure over the 5-week treatment period
Time frame: 5 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOC and Advanced Bioengineered Skin Substitute | Proportion of Complete Closure | 6 Participants |
| SOC and Active Comparator | Proportion of Complete Closure | 3 Participants |
Secondary
Time to Achieve Complete Wound Closure
The time to achieve complete wound closure of the target ulcer by the end of 5 weeks
Time frame: 5 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SOC and Advanced Bioengineered Skin Substitute | Time to Achieve Complete Wound Closure | 28.3 Days |
| SOC and Active Comparator | Time to Achieve Complete Wound Closure | 26.8 Days |
Other Pre-specified
Safety Analysis for Treatment Emergent Adverse Events
The number and type of Treatment Emergent Adverse Events
Time frame: 5 weeks