A Phase I, Single-blind, Randomized Study of the Safety and Efficacy of Cellularized Integra® Using Autologous Burn-derived Stem Cells

Study Overview
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Brief Summary
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Burn injuries are one of the most severe skin injuries and lead to a complex wound healing response. When the skin is wounded, stem cells in the skin must respond fast to help repair the injured tissue. The damaged skin of burn patients contains cells that are still alive and have typical stem cell characteristics. Because stem cells are so important for wound healing, the investigators have combined them with an existing skin substitute, Integra®, to examine the potential wound healing benefits of these stem cells. This is an investigational treatment and a first in-human trial. The purpose of this study is to test the safety of using a patient's own stem cells combined with Integra®, which the investigators call Integra®-Stem Cells (Integra®-SC). The investigators hypothesize that Integra®-SC will result in improved wound healing, better scar quality, and decreased scar formation at one-year post-injury.

Official Title
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A Phase I, Single-blind, Randomized Study of the Safety and Efficacy of Cellularized Integra® Using Autologous Burn-derived Stem Cells

Conditions
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Burns

Intervention / Treatment
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* Device: Integra®
* Device: Integra®-SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years. Total body surface area (TBSA) ≥ 5%. Full-thickness burn requiring operative procedures. Admitted ≤ 120 hours following burn. Injury location includes a contralateral area. Exclusion Criteria: All participants meeting any of the following exclusion criteria at baseline will be excluded from participation in this study: Patients who are moribund. Known infection with any of the following: Human Immunodeficiency Virus (HIV), Hepatitis B, Hepatitis C, Human T-lymphotropic Virus (HTLV), Syphilis, or West Nile Virus. Injury location limited to face and/or hands. Pregnancy. Active cancer and currently undergoing treatment.

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
Interventional Model Description: Integra®-SC will be applied to one area of the body and acellular Integra® will be applied to another. Determination of the location of the Integra® control or Integra®-SC application will be assigned using simple randomization. The wound areas will be appropriately matched for body surface area and depth of the wound.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>After removal of the temporary wound coverage (allograft), Integra® is applied directly onto the wound surface. | Device: Integra®<br>* A commercially available dermal bovine matrix that is widely used for wound and burn care, Integra® Dermal Regeneration Template licensed device (Medical Device Active License Listing No. 229).<br>|
| Experimental: Integra®-SC<br>After removal of the temporary wound coverage (allograft), Integra®-SC is applied to the contralateral area of the site where Integra® is applied. | Device: Integra®-SC<br>* A combination of Integra® incorporated with 5,000-20,000 cells/cm2 of autologous burned derived stem cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Number of participants with surgical site infections | The primary outcome of this study is safety. In order to assess the safety of Integra®-SC, surgical site infections that require an additional (unplanned) operation will be recorded as an in-hospital complication. | Acute hospitalization (1-4 months post admission depending on severity of injury) | 
| Safety - Number of participants with non-healing wounds | The primary outcome of this study is safety. In order to assess the safety of Integra®-SC, non-healing wounds that require an additional (unplanned) operation will be recorded as an in-hospital complication. | Acute hospitalization (1-4 months post admission depending on severity of injury) | 
| Safety - Number of patients with poor scarring requiring additional (unplanned) operation | The primary outcome of this study is safety. In order to assess the safety of Integra®-SC, poor scarring requiring an additional (unplanned) operation will be recorded as a late-onset complication. | Discharge to to 1 year post-discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of wound healing | Time from wound excision to 95% healing of the burned area will be recorded. Photography and evaluation of wounds will occur at enrollment, operation days, dressing take-downs, and discharge from hospital. | Acute hospitalization (1-4 months post admission depending on severity of injury) | 
| Quality of skin regeneration - Arterial bleeding from the wound site | Arterial bleeding from the wound site will be recorded to assess the quality of skin regeneration. Photography and evaluation of wounds will occur at enrollment, operation days, dressing take-downs, and discharge from hospital. | Acute hospitalization (1-4 months post admission depending on severity of injury) | 
| Quality of skin regeneration - Signs of wound infection | Classic signs of wound infection will be recorded to assess the quality of skin regeneration. Photography and evaluation of wounds will occur at enrollment, operation days, dressing take-downs, and discharge from hospital. | Acute hospitalization (1-4 months post admission depending on severity of injury) | 
| Quality of skin regeneration - Detachment of Integra®-SC | The detachment of the entire Integra®-SC from the wound site will be recorded to assess the quality of skin regeneration. Photography and evaluation of wounds will occur at enrollment, operation days, dressing take-downs, and discharge from hospital. | Acute hospitalization (1-4 months post admission depending on severity of injury) | 
| Quality of skin regeneration - Abnormal scar formation | The formation of hypertrophic scars or keloids will be recorded to assess the quality of skin regeneration. Photography and evaluation of wounds will occur at enrollment, operation days, dressing take-downs, and discharge from hospital. | Acute hospitalization (1-4 months post admission depending on severity of injury) | 
| Scar Formation - Vascularity of the healed area | Vascularity of the healed area is assessed as part of the Vancouver Scar Scale to evaluate scar formation over time. Vascularity is scored from 0 to 3, with higher scores indicating worse outcomes. Photography and evaluation of treated area for scar formation will be assessed at outpatient follow-ups at approximately 30 days, 60 days, 90 days, 180 days, and 365 days post-discharge (with 2-4 weeks deviation). Follow-ups typically take place in-person at clinic visits, but may take place online via a secure platform. | Discharge to 1 year post-discharge | 
| Scar formation - Pigmentation of the healed area | Pigmentation of the healed area is assessed as part of the Vancouver Scar Scale to evaluate scar formation over time. Pigmentation is scored from 0 to 2, with higher scores indicating worse outcomes. Photography and evaluation of treated area for scar formation will be assessed at outpatient follow-ups at approximately 30 days, 60 days, 90 days, 180 days, and 365 days post-discharge (with 2-4 weeks deviation). Follow-ups typically take place in-person at clinic visits, but may take place online via a secure platform. | Discharge to 1 year post-discharge | 
| Scar formation - Pliability of the healed area | Pliability of the healed area is assessed as part of the Vancouver Scar Scale to evaluate scar formation over time. Pliability is scored from 0 to 5, with higher scores indicating worse outcomes. Photography and evaluation of treated area for scar formation will be assessed at outpatient follow-ups at approximately 30 days, 60 days, 90 days, 180 days, and 365 days post-discharge (with 2-4 weeks deviation). Follow-ups typically take place in-person at clinic visits, but may take place online via a secure platform. | Discharge to 1 year post-discharge | 
| Scar formation - Height of the healed area | The height of the healed area is assessed as part of the Vancouver Scar Scale to evaluate scar formation over time. Height is scored from 0 to 3, with higher scores indicating worse outcomes. Photography and evaluation of treated area for scar formation will be assessed at outpatient follow-ups at approximately 30 days, 60 days, 90 days, 180 days, and 365 days post-discharge (with 2-4 weeks deviation). Follow-ups typically take place in-person at clinic visits, but may take place online via a secure platform. | Discharge to 1 year post-discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem Cells, Wound Healing, Cicatrix, Skin, Artificial