Clinical trial NCT00587223: Safety and Efficacy of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa (EB)
Official title: A Prospective, Multicenter, Within Subject Controlled Study to Evaluate the Effect of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epidermolysis Bullosa, Junctional
Epidermolysis Bullosa Dystrophica
Lead sponsor: Organogenesis
Sponsor class: INDUSTRY
First posted: 2008-01-07
Enrollment: 1
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Proportion of Wounds First Achieving 100% Epithelialization of Tissue With the Absence of Drainage (i.e. Complete Wound Closure) Through Study Week 12
timeFrame: Through 12 weeks
Secondary outcomes:
measure: Time Until Complete Closure
timeFrame: through 12 weeks
measure: Rate of Complete Wound Closure Over Time
timeFrame: through 12 weeks
measure: Recurrence of Epidermolysis Bullosa (EB) Lesions
timeFrame: through 12 months
measure: Reduction of Intensity of Pain
timeFrame: through 12 weeks
measure: Proportion of Wounds Experiencing an Adverse Event
timeFrame: through 12 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Miami
country: United States
facility: University of Miami - Miller School of Medicine
state: Florida
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital of Cincinnati
state: Ohio
city: Houston
country: United States
facility: University of Texas
state: Texas
Study officials:
affiliation: University of Miami
name: Elizabeth Alvarez- Connelly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Organogenesis Inc.
name: Damien Bates, MD, PhD, FRACS (Plast.)
role: STUDY_DIRECTOR
References: