A Post-Marketing Clinical Study of Apligraf for Venous Leg Ulcers

Study Overview
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Brief Summary
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Single site clinical study utilizing the novel technology of microarrays to identify and characterize the molecular mechanisms through which Apligraf promotes healing of venous leg ulcers.

Official Title
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A Prospective, Single-Site Study to Identify and Characterize the Molecular Mechanisms of Apligraf in Non-healing Wounds of Subjects With Venous Leg Ulcers

Conditions
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Varicose Ulcer

Intervention / Treatment
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* Device: Apligraf


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has non-infected partial or full-thickness venous leg ulcer for a duration of four weeks or greater which has not adequately responded to conventional therapy Stage II or III ulcer as defined by the IAET/WOCN ulcer classification guide listed in Appendix IV. Subject is female and 18 years of age or older. Subject with venous leg ulcer (target ulcer) between 5 - 40 cm2 in size. 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. Subject and/or legal guardian must be able and willing to follow study procedures and instructions. Exclusion Criteria: Subject whose target ulcer has healed 60% 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. Subjects who are being treated with VAC® (Vacuum Assisted Closure™) Therapy. Subject has arterial disease as determined by an Ankle Brachial Index (ABI ) of <0.65. Subject with any systemic condition like uncontrolled diabetes mellitus (glycosylated HbA1C > 12%), cancer (biopsy confirmed active malignancy), positive HIV test, or any disorder(s) that may compromise wound healing. Subjects who are currently receiving, or have received at any time within one month prior to entry into the study, corticosteroids (>15 mg/day), immunosuppressive agents, radiation therapy, hemodialysis or chemotherapy. Anticipated use of the above agents will exclude subjects from entry into the study. Clinical vasculitis, severe rheumatoid arthritis, and other collagen vascular diseases. Signs and symptoms of cellulitis or osteomyelitis. Necrotic or avascular ulcer beds. Venous leg ulcer with exposed bone, tendon or fascia. Subject with the presence of recent infections in the area intended for treatment. 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 with liver (ALT/SGPT, ALP, AST/SGOT, bilirubin, Albumin, total protein, LDH) and/or renal function (BUN and creatinine) tests greater than 2 x upper limit of normal (ULN) or Albumin < 2.5 mg/dL. Subject enrolled in any wound or investigational device study for any disease within the past four weeks. Subject previously treated at target site with Apligraf, Dermagraft or any other cell therapy at the target site. 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: 18 Years

Sexes Eligible for Study
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Female

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: 1<br>Apligraf | Device: Apligraf<br>* Applied at Day 0, possible re-application at Week 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To use the novel technology of microarrays to identify and characterize the molecular mechanisms through which Apligraf promotes healing of venous leg ulcers. |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine how venous leg ulcer (VLU) wounds transition from chronic to acute wound healing |  | 2 weeks | 
| Examine how Apligraf rescues deficiencies of chronic wounds (VLU) and promotes transition from chronic to acute wound |  | 2 weeks | 
| Determine growth factors induced by Apligraf in the wound |  | 2 weeks | 
| Determine growth factors suppressed by Apligraf in the wound |  | 2 weeks | 
| Safety endpoints assessed by monitoring adverse events |  | 5 months |