Safety and Efficacy of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa (EB)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the use of Apligraf for the treatment of nonhealing wounds in subjects with dystrophic or junctional epidermolysis bullosa. Apligraf will be evaluated for efficacy and safety compared to a conventional nonadherent dressing. A matched-pair design will be used to evaluate Apligraf treatment versus conventional treatment in 68 study pairs.

Official Title
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A Prospective, Multicenter, Within Subject Controlled Study to Evaluate the Effect of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa

Conditions
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Epidermolysis Bullosa, Junctional, Epidermolysis Bullosa Dystrophica

Intervention / Treatment
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* Device: Apligraf
* Other: Standard dressing regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is between 2 and 65 years of age. Subject with clinical and histological diagnosis of junctional or dystrophic EB with documented electron microscopy or immunofluorescence microscopy. Subject has at least two non-adjacent EB lesions, at least 4 cm apart. The two selected EB lesions must be relatively matched in terms of diagnosis, location, level of erosion and size. Lesions may be on the same limb. Subject with dystrophic or junctional EB lesions between 10-44 cm2 present for at least 6 weeks. For the purposes of this study, a lesion is defined as a wound resulting from a post blister erosion. Subject who is a female of child-bearing potential (females >10 years of age) must have a documented negative urine or serum pregnancy test. Sexually active females must be practicing a medically proven form of contraception during the course of the study period. Subject or legal guardian must have read, understood and signed an institutional review board (IRB) approved Informed Consent Form or Assent Form. Subject and/or legal guardian must be able and willing to follow study procedures and instructions. Exclusion Criteria: Subject with lesions only on the soles, posterior thigh or gluteus maximus. Subject whose lesion has healed 20% or greater in area from post debridement (if applicable) Baseline Screen (Visit 1) to post debridement Day 0 (Visit 2) as determined by wound tracings. Subject with uncontrolled diabetes mellitus (glycosylated HbA1C > 10%), cancer (biopsy confirmed active malignancy), or positive HIV test. Subject is a child (<18 years of age) who is currently receiving or has received oral steroid therapy exceeding a total daily dose of 0.5mg/kg for more than two weeks, radiation or other immuno-suppressive therapy which would interfere with wound healing within the past four weeks. Subject is an adult (>18 years of age) who is currently receiving or has received chronic high dose steroid therapy exceeding a total daily dose of 20mg for more than two weeks, radiation or other immuno-suppressive therapy which would interfere with wound healing within the past four weeks. Subject who is currently on or has received topical steroidal therapy within 30 days before screening. Inhaled steroids are allowed. Subject with the presence of acute infections in the areas intended for treatment. Subject with a history of squamous cell carcinoma. Known hypersensitivity to bovine collagen or to the components of the Apligraf agarose shipping medium. Subject who is lactating or pregnant (hCG positive as determined by lab testing). Subject is a child (<18 years of age) with liver (ALT/SGPT, ALP, AST/SGOT, bilirubin, total protein, LDH) and/or renal function (BUN and creatinine) tests > 2 x upper limit of normal (ULN). Albumin < 2.0 mg/dL. Subject is an adult (>18 years of age) with liver (ALT/SGPT, ALP, AST/SGOT, bilirubin, total protein, LDH) and/or renal function (BUN and creatinine) tests > 2 x upper limit of normal (ULN). Albumin < 2.0 mg/dL. Subject enrolled in any wound or investigational device study for any disease within the past four weeks. Subject who has received an investigational drug or biological treatment within three months. Subject previously treated with Apligraf, Dermagraft or any other cell therapy at the target sites. Subject with a history of alcohol or substance abuse within the previous year, which could interfere with study compliance such as inability to attend scheduled study visits or compliance with home dressing changes. Subject who, in the opinion of the investigator, for any reason other than those listed above, will not be able to complete the study per protocol.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Apligraf (a living bilayered cell therapy product) | Device: Apligraf<br>* Up to 3 applications: Day 0, Month 1, Month 2.<br>|
| Active Comparator: 2<br>Dressing regimen comprised of a primary nonadherent dressing, nonstick gauze and standard dressing retainer. | Other: Standard dressing regimen<br>* Dressing regimen will be comprised of a primary nonadherent dressing, nonstick gauze and standard dressing retainer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Wounds First Achieving 100% Epithelialization of Tissue With the Absence of Drainage (i.e. Complete Wound Closure) Through Study Week 12 |  | Through 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Until Complete Closure |  | through 12 weeks | 
| Rate of Complete Wound Closure Over Time |  | through 12 weeks | 
| Recurrence of Epidermolysis Bullosa (EB) Lesions |  | through 12 months | 
| Reduction of Intensity of Pain |  | through 12 weeks | 
| Proportion of Wounds Experiencing an Adverse Event |  | through 12 months |