Recessive Dystrophic Epidermolysis Bullosa
Conditions
Brief summary
Recessive dystrophic epidermolysis bullosa (RDEB) is a subtype of epidermolysis bullosa (EB), an inherited skin condition that presents with blistering skin. The Spincare device, developed by Nanomedic, is the first portable tool that delivers a non-invasive, non-therapeutic electrospun, nanofibrous matrix dressing to wounds to promote healing. The aim of this study is to determine the suitability of this device in RDEB wounds and assess its wound healing properties, safety and tolerability.
Detailed description
Investigators will aim to recruit a mixture of adult and pediatric patient. However, the first patient that is recruited would be an adult to collect safety and efficacy data before enrolling pediatric patients. Screening- Patients would be screened over the phone to assess if they meet the inclusion and exclusion criteria. Thereafter a virtual meeting via a secure virtual platform is arranged for the patient to review the consent form and sign. Wounds will be assessed to see if they meet the inclusion and exclusion criteria. Day 0 - A full body wound examination will be performed by the investigator and target wound areas will be marked. All eligible wound sites will be randomized for matrix treatment versus standard of care wound care (at least 6 wounds, or 3 wound pairs). The matrix will be applied to randomized treatment wounds, along with a non-adhesive bandage as a protective layer. Reapplication of matrix treatment may be required depending on how well the matrix has propagated. At the time of matrix application, the investigator will score amount of wound burning, pain, or other adverse events. Non-treated wounds will have the patient's standard of care, non-adhesive bandage applied. Subjects and caregivers will be trained on how take photos. The aim is to capture photos of the wounds, pain and itch scores at least every 2 weeks. Surveys will be completed by the caregiver to see if they notice any difference in the wounds with the spray treatment. This will be completed together with the patient's pain and itch surveys. Day 1 and optional Day 2- Clinic Visits: A wound examination will be performed in clinic. The investigator will assess the adherence of the matrix, and any adverse events (AEs). Day 2 visit may be necessary at the discretion of the investigators especially if any adverse events have occurred. Months 1, 2, 3, 4 Visits: clinic attendance for patients with EB may be stressful and inconvenient due to their complex wound pattern and dressing changes. Keeping their safety and dignity as a priority the remaining visits as home visits are conducted with telehealth assessment. This will be done over a secure virtual platform or phone call whereby the assessors will be consulting remotely from a private Stanford based office room. The caregiver will apply the matrix to randomized, treated wounds (up to once a week application is allowed, the date and reason for reapplication is required)(additional interim visits/telehealth assessment and reapplication of matrix treatment may occur at Week 1, Week 2, Week 6, Week 10 and Week 14 or more frequently if deemed necessary). Patients will be asked to record the date each time the Spincare was applied. Photographs will be taken at those timepoints, and investigators will use Telehealth to monitor for healing and safety reporting (additional weekly photographs are encouraged). At the time of matrix application, the amount of wound burning, pain, or other adverse events will be scored Month 4 Telehealth/End of study Visit: The investigator will virtually assess wound healing compared to baseline photographs in the treated and control wounds. Digital photographs of the treatment and control wounds will be taken with a ruler by the caregiver and sent to the investigator. All wound photos will be reviewed via RedCAP. Wound swabs will be collected from treated and untreated wounds prior to spray treatment and at Month 2 and Month 4. Participants may be offered the choice to complete surveys online and/or upload photos via Stanford RedCap. Open-Label (Extension) Phase: After the completion of the 4-month randomized phase, patients will choose to enroll in an open Open-Label Phase for an additional 4 months. Investigators will conduct remote monitoring on a monthly basis to assess adverse events and wound healing. Participants will complete surveys regarding their pain and itch, offer updates on their medical history, and provide information about concurrent medications. No blood draws, wound cultures and in person visits will be required during the Open-Label Phase.
Interventions
DEVICESpincare matrix
The Spincare device, developed by Nanomedic, is the first portable tool that delivers a non-invasive, non-therapeutic electrospun, nanofibrous matrix dressing to wounds to promote healing.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Intra-patient randomization of wound pairs into control wounds vs matrix treated wounds, followed by an open-label (extension) phase without randomization
Eligibility
Sex/Gender
ALL
Age
6 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Clinical and/or genetic diagnosis of RDEB by a dermatologist * Age 6 years or older willing and able to give consent/assent * At least 6 wounds (3 wound pairs) each with an area of 10cm2 or greater located at any site (excluding face and genital skin) * Wounds must be present for at least 4 weeks and able to be classified as recurrent wounds (wounds that heal within 12 weeks but then re-blister) vs chronic open (older than 12 weeks)
Exclusion criteria
* Actively infected wounds with pus (colonized wounds are eligible) * Wounds that have had squamous cell carcinoma (SCC) * Wounds on the face and genitals * Wounds that have been treated with investigational therapies in the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Wounds With Greater Than 90% Wound Closure at 4 Months | Baseline to month 4 of the randomized phase | The primary endpoint was comparison of the duration of wound closure of matrix-treated wounds vs control wounds measured as the number of wounds achieving greater than 90% wound closure within 4 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event Profile Characterization | 4-month randomized period followed by 4-month open-label period | Comparison of application site adverse events (burning, erythema, pain) between matrix-treated wounds vs control wounds after application. For this outcome, adverse events were collected per wound; events affecting the participant but not the wound are not included. |
| Change From Baseline in Wound Pain Scale Score Assessment | months 1, 2, 3, and 4 of the randomized phase | Pain was assessed using the Wong-Baker Faces scale (prior to matrix application). The scale consists of six faces that range from 0 (no pain at all, favorable outcome) to 10 (worst pain imaginable, worst outcome). Participants rated each wound using this scale, and scores were summed and averaged for each time point, resulting in an overall score range of 0 (no pain at all) to 10 (worst pain imaginable). |
| Change in Wound Itch Scale Score Assessment | months 1, 2, 3, and 4 of the randomized phase | Wound itch scores were assessed using the Itch NRS (prior to matrix application). The Itch NRS is a numerical rating scale from 0 to 10. Participants rated each wound using this scale, and scores were summed and averaged for each time point, resulting in an overall score of 0 to 10 (higher scores correspond to more pain). |
| Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | months 1, 2, 3, and 4 of the randomized phase | Comparison of wounds that reach \>50% healing from baseline in matrix vs control (standard-of-care treated) wounds, per clinician assessment. |
| Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | months 1, 2, 3, and 4 of the randomized phase | Comparison of wounds that reach \>70% healing from baseline in matrix-treated vs control wounds, per clinician assessment. |
Countries
United States
Participant flow
Recruitment details
Patients aged 6-65 years with a clinical and/or genetic diagnosis of recessive dystrophic epidermolysis bullosa were screened over the phone. If eligible a virtual meeting was organized, and patients were asked to review and sign the informed consent form after which the wounds were assessed to determine suitability. This target population was chosen due to their large painful wounds usually resistant to conventional treatment and would benefit most from Spincare matrix treatment.
Pre-assignment details
On Day 0, the investigator conducted an in-person full body skin examination and collected wound measurements to verify eligibility. The participant's wounds were assessed for signs of infection, and target wound areas were identified. Wounds that were actively infected with pus were excluded before randomization and the application of the matrix.
Participants by arm
| Arm | Count |
|---|---|
| Matrix-Treated Wounds (Randomized Period) Wounds that were randomized to receive matrix application. | 6 |
| Matrix-Treated Wounds (Randomized Period) Wounds that were randomized to receive matrix application. | 21 |
| Standard of Care-Treated Wounds (Randomized Period) Wounds that were randomized to receive standard of care treatment. | 6 |
| Standard of Care-Treated Wounds (Randomized Period) Wounds that were randomized to receive standard of care treatment. | 21 |
| Open Label - Matrix-Treated Wounds that were selected to receive matrix application, no randomization, no controls. | 1 |
| Open Label - Matrix-Treated Wounds that were selected to receive matrix application, no randomization, no controls. | 5 |
| Total | 60 |
Baseline characteristics
| Characteristic | Matrix-Treated Wounds (Randomized Period) | Standard of Care-Treated Wounds (Randomized Period) | Open Label - Matrix-Treated | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 1 Participants | 9 Participants |
| Age, Continuous | 21 years | 21 years | 33 years | 21 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 1 Participants | 11 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 1 participants | 6 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 1 | 0 / 6 | 0 / 1 |
| other Total, other adverse events | 3 / 6 | 3 / 6 | 0 / 1 | 5 / 6 | 1 / 1 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 1 | 1 / 6 | 0 / 1 |
Outcome results
Primary
Number of Wounds With Greater Than 90% Wound Closure at 4 Months
The primary endpoint was comparison of the duration of wound closure of matrix-treated wounds vs control wounds measured as the number of wounds achieving greater than 90% wound closure within 4 months
Time frame: Baseline to month 4 of the randomized phase
Population: Participants with month 4 data
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds With Greater Than 90% Wound Closure at 4 Months | 0 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds With Greater Than 90% Wound Closure at 4 Months | 3 Wounds |
p-value: 0.21t-test, 2 sided
Secondary
Adverse Event Profile Characterization
Comparison of application site adverse events (burning, erythema, pain) between matrix-treated wounds vs control wounds after application. For this outcome, adverse events were collected per wound; events affecting the participant but not the wound are not included.
Time frame: 4-month randomized period followed by 4-month open-label period
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Matrix-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Any Adverse Event | 11 wounds |
| Matrix-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Bacterial Colonization | 0 wounds |
| Matrix-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Pain of Skin, requiring medication to treat | 3 wounds |
| Matrix-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Skin Infection (non-serious) | 6 wounds |
| Matrix-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Pruritis, requiring medication to treat | 2 wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Skin Infection (non-serious) | 5 wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Any Adverse Event | 10 wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Pruritis, requiring medication to treat | 0 wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Pain of Skin, requiring medication to treat | 0 wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Adverse Event Profile Characterization | Bacterial Colonization | 4 wounds |
| Matrix-Treated Wounds (Open Label Phase) | Adverse Event Profile Characterization | Pruritis, requiring medication to treat | 0 wounds |
| Matrix-Treated Wounds (Open Label Phase) | Adverse Event Profile Characterization | Skin Infection (non-serious) | 0 wounds |
| Matrix-Treated Wounds (Open Label Phase) | Adverse Event Profile Characterization | Bacterial Colonization | 0 wounds |
| Matrix-Treated Wounds (Open Label Phase) | Adverse Event Profile Characterization | Any Adverse Event | 0 wounds |
| Matrix-Treated Wounds (Open Label Phase) | Adverse Event Profile Characterization | Pain of Skin, requiring medication to treat | 0 wounds |
Secondary
Change From Baseline in Wound Pain Scale Score Assessment
Pain was assessed using the Wong-Baker Faces scale (prior to matrix application). The scale consists of six faces that range from 0 (no pain at all, favorable outcome) to 10 (worst pain imaginable, worst outcome). Participants rated each wound using this scale, and scores were summed and averaged for each time point, resulting in an overall score range of 0 (no pain at all) to 10 (worst pain imaginable).
Time frame: months 1, 2, 3, and 4 of the randomized phase
Population: Participants with available data at the respective time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matrix-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 1 | -1.43 score on a scale | Standard Deviation 2.18 |
| Matrix-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 3 | -1.45 score on a scale | Standard Deviation 3.62 |
| Matrix-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 2 | 0.43 score on a scale | Standard Deviation 3.56 |
| Matrix-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 4 | -1.64 score on a scale | Standard Deviation 2.71 |
| Matrix-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Baseline | 3.143 score on a scale | Standard Deviation 3.38 |
| Standard of Care-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 4 | -1.64 score on a scale | Standard Deviation 3.8 |
| Standard of Care-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Baseline | 2.762 score on a scale | Standard Deviation 3.71 |
| Standard of Care-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 1 | -1.52 score on a scale | Standard Deviation 3.64 |
| Standard of Care-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 2 | -1.71 score on a scale | Standard Deviation 3.42 |
| Standard of Care-Treated Wounds (Randomized Period) | Change From Baseline in Wound Pain Scale Score Assessment | Change at Month 3 | -0.73 score on a scale | Standard Deviation 4.96 |
Secondary
Change in Wound Itch Scale Score Assessment
Wound itch scores were assessed using the Itch NRS (prior to matrix application). The Itch NRS is a numerical rating scale from 0 to 10. Participants rated each wound using this scale, and scores were summed and averaged for each time point, resulting in an overall score of 0 to 10 (higher scores correspond to more pain).
Time frame: months 1, 2, 3, and 4 of the randomized phase
Population: Participants with available data at the respective time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matrix-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 1 | -1.19 units on a scale | Standard Deviation 1.24 |
| Matrix-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 3 | -1.36 units on a scale | Standard Deviation 1.55 |
| Matrix-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 2 | -0.85 units on a scale | Standard Deviation 2.75 |
| Matrix-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 4 | -1.27 units on a scale | Standard Deviation 1.59 |
| Matrix-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Baseline | 2.86 units on a scale | Standard Deviation 2.55 |
| Standard of Care-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 4 | -0.18 units on a scale | Standard Deviation 1.73 |
| Standard of Care-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Baseline | 2.10 units on a scale | Standard Deviation 2.17 |
| Standard of Care-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 1 | -0.71 units on a scale | Standard Deviation 1.27 |
| Standard of Care-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 2 | -0.43 units on a scale | Standard Deviation 1.1 |
| Standard of Care-Treated Wounds (Randomized Period) | Change in Wound Itch Scale Score Assessment | Change at Month 3 | 0.27 units on a scale | Standard Deviation 1.65 |
Secondary
Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment
Comparison of wounds that reach \>50% healing from baseline in matrix vs control (standard-of-care treated) wounds, per clinician assessment.
Time frame: months 1, 2, 3, and 4 of the randomized phase
Population: Participants with available data at the respective time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 1 | 8 Wounds |
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 2 | 4 Wounds |
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 3 | 4 Wounds |
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 4 | 1 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 4 | 5 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 1 | 7 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 3 | 4 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >50% Healing From Baseline Per Investigator Assessment | Month 2 | 5 Wounds |
Comparison: Wounds that reach \>50% healing from baseline per investigator assessment at Month 1p-value: 1t-test, 2 sided
Comparison: Wounds that reach \>50% healing from baseline per investigator assessment at Month 2p-value: 1t-test, 2 sided
Comparison: Wounds that reach \>50% healing from baseline per investigator assessment at Month 3p-value: 1t-test, 2 sided
Comparison: Wounds that reach \>50% healing from baseline per investigator assessment at Month 4p-value: 0.15t-test, 2 sided
Secondary
Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment
Comparison of wounds that reach \>70% healing from baseline in matrix-treated vs control wounds, per clinician assessment.
Time frame: months 1, 2, 3, and 4 of the randomized phase
Population: Number of wounds that reach \>70% healing from baseline in matrix-treated vs control wounds
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 1 | 4 Wounds |
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 3 | 1 Wounds |
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 2 | 3 Wounds |
| Matrix-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 4 | 0 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 2 | 4 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 1 | 5 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 4 | 4 Wounds |
| Standard of Care-Treated Wounds (Randomized Period) | Number of Wounds That Reach >70% Healing From Baseline Per Investigator Assessment | Month 3 | 3 Wounds |
Comparison: Wounds that reach \>70% healing from baseline per investigator assessment at Month 1p-value: 1t-test, 2 sided
Comparison: Wounds that reach \>70% healing from baseline per investigator assessment at Month 2p-value: 1t-test, 2 sided
Comparison: Wounds that reach \>70% healing from baseline per investigator assessment at Month 3p-value: 0.59t-test, 2 sided
Comparison: Wounds that reach \>70% healing from baseline per investigator assessment at Month 4p-value: 0.09t-test, 2 sided