Safety of Extracellular Vesicles for Burn Wounds

Study Overview
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Brief Summary
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Treatment of patients with deep second degree burns of the skin with extracellular vesicles (EV) isolated from bone marrow derived mesenchymal stem cells.

Detailed Description
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This study is designed to examine the safety and efficacy, in 10 patients of administration of allogeneic MSC EV to deep second degree burn wounds. The dose level delivered will be approximately 1 X 107 EV particles for each cm2 treated area. Wounds eligible for treatment will not exceed 600 cm2 per wound or collection of wounds in a defined anatomical area (e.g., arm, leg, chest) treated. Patients with 20% or greater TBSA in total (3700 cm2 in a 70 kg, 175 cm subject) will be ineligible to participate in the study. The first treatment will be administered within 48 hours of the burn injury. Two additional administrations of EV will be given approximately one week (day 5-7 post-injury) and two weeks after the first treatment (unless the wound is fully closed, in which case the patient will continue to be monitored at weekly intervals through 5 weeks, then at 8, 12, 26, and 54 weeks). Safety will be assessed by collection of adverse event data. The potential for wound healing efficacy will be evaluated by recording the percent of burns re-epithelialized within 8 weeks as well as the time to complete closure. Wound closure will be defined as complete re-epithelialization that is not subject to re-injury during dressing changes or as a result of normal daily activities (e.g., wearing clothing, eating, sleeping). The potential for tissue regeneration and restoration of pigmentation, hair growth and skin texture will be evaluated by scoring healing and scar formation using POSAS. Assessment of the potential for prevention of conversion will be done using LDI. Deep second degree wounds presenting at screening that are assessed to be deeper by LDI at the 5-7 day reading than at the initial evaluation in the first 48 hours will be considered to have undergone conversion. Exploratory endpoints will include monitoring for the presence of an immunologic response in recipients.

Official Title
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A Pilot Safety Study of Mesenchymal Stem Cell Derived Extracellular Vesicles for the Treatment of Burn Wounds.

Conditions
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Burns

Intervention / Treatment
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* Drug: AGLE-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen years of age or older with deep second degree thermal burn wounds Index burn injury within the prior 48 hours Subjects must understand and be willing and able to give written informed consent Subjects must agree to have blood draws performed per protocol Subjects must be accessible for wound treatment and assessment visits Males and females must agree to use an acceptable method of contraception. Exceptions will be females of non-childbearing age and monogamous males who are partners of females of non-childbearing age. Acceptable methods of birth control include; history of sterilization, oral contraceptives, depo-progesterone injections, a barrier contraceptive such as a condom with or without spermicide cream or gel, diaphragms or cervical cap with or without spermicide cream or gel, or an intrauterine device (IUD). Maximum index wound size at screening limited to single or multiple wounds (in a defined anatomical area) cumulatively ≤ 600 cm2. Minimum wound size at screening: 30 cm2. Other wounds may be present that are treated separately from this protocol subject to the maximum TBSA exclusion criteria listed below. Exclusion Criteria: Solely first degree or solely third degree burns Cumulative burn area ≥ 20% TBSA (20% TBSA corresponds to 3700 cm2 in a 70 kg, 175 cm subject) Burns that occur over a previous scar Chemical, radiation, or electrical burns Subjects with superficial second degree burn who are expected to heal within 2 weeks with standard therapy Evidence of active infection at the wound site Evidence of significant wound healing prior to treatment Burn wounds requiring surgery (other than debridement), or skin grafting Wound exclusively located in the area of fingers, toes, face, or perineum Wound that extends > 50% across one or more joints Have any requirement for the use of systemic steroids or immunosuppressive medications Subjects allergic to human albumin, streptomycin, or penicillin Be a pregnant female or nursing mother Subjects who are known or found to be HIV positive History of alcohol or substance abuse requiring treatment within the past 12 months. Severe medical conditions Malignancy (other than non-melanoma skin cancer) not in remission or in remission less than 5 years Life expectancy less than two years Severe cardiopulmonary disease restricting ambulation to the clinical facility WBC <3 or > 20 x109/L, Hgb < 9g/dL, platelet count 100x109/L or less, serum creatinine > 1.5 times the upper normal limit, AST or ALT > 2.4 times upper normal limit Known history of coagulopathy Subjects who have a reasonable likelihood of being a recipient of tissue or organ transplantation History of poor compliance, unreliability

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AGLE-102<br>AGLE-102, bone marrow mesenchymal stem cell derived extracellular vesicles (EVs) | Drug: AGLE-102<br>* AGLE-102, bone marrow mesenchymal stem cell derived extracellular vesicles (EVs)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine the safety of applying up to three applications of EVs to deep 2nd degree burn wounds up to 600 cm2 | Examine the safety of applying up to three applications of EVs to deep 2nd degree burn wounds up to 600 cm2 by evaluating the number of participants with treatment-related adverse events as assessed cy CTCAE v4.0 | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if administration of EVs can promote wound healing by serial wound measurements | Determine if administration of EVs can promote wound healing by serial wound measurements; tissue regeneration as evidenced by restoration of pigmentation and hair growth by serial photography; and skin texture assessment the Patient and Observer Scar Assessment Scale (scale of 1 to 10, where 10 is a worse outcome). | 8 weeks | 
| Laser Doppler will assess differences in dermal perfusion rates between control (unburned) and treated burn tissues. | Laser Doppler will assess differences in dermal perfusion rates between control (unburned) and treated burn tissues. | 1 year |