Safety and Efficacy of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa (EB)
Condition: Epidermolysis Bullosa, Junctional; Epidermolysis Bullosa Dystrophica
MeSH terms: Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica; Epidermolysis Bullosa, Junctional
Intervention: Apligraf; Standard dressing regimen
Intervention description: Up to 3 applications: Day 0, Month 1, Month 2.; Dressing regimen will be comprised of a primary nonadherent dressing, nonstick gauze and standard dressing retainer
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 2 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.