A Pilot Study of Apligraf for the Treatment and Prevention of Recurrence of Excised Keloids

Study Overview
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Brief Summary
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This pilot study will assess the safety and efficacy of Apligraf in the healing and recurrence of keloids post surgical shave excision in patients with clinically diagnosed keloids.

Official Title
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A Prospective, Randomized, Controlled Pilot Study of Apligraf for the Treatment and Prevention of Recurrence of Excised Keloids

Conditions
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Keloid

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 18 and 65 years of age. Subject or legal guardian has read, understood, and signed appropriate Institutional Review Board (IRB) approved informed consent, photography release form and HIPAA consent in their own language. Subject with 1 keloid measuring between 1 cm2 - 40 cm2 as assessed by the Investigator, present for at least 6 months and a Beausang Scar scale combined score of 5 or greater. Subject is a male or female who must have a documented negative urine pregnancy test if of child bearing potential. Sexually active females must be practicing a medically proven form of contraception during the course of the study period. Subject and/or legal guardian must be able and willing to follow study procedures and instructions. Subject and/or legal guardian must be able and willing to return for follow-up study visits. Subject agrees to not use a keloid medication or injection treatment for four weeks prior to Day 0. Subject agrees not to use any other keloid treatments for the duration of the study. Subject is otherwise healthy as assessed and determined by the Investigator Exclusion Criteria: Subject is suffering from a condition likely to require medical attention, including administration of any treatment which in the opinion of the Investigator could influence the results of the study. Subject with any systemic condition like uncontrolled diabetes mellitus (glycosylated hemoglobin, HbA1C > 10%), cancer (biopsy confirming active malignancy), positive HIV test, or any disorder(s) that may compromise wound healing. Subject is suffering from an abnormal skin condition on the affected area not usually associated with keloids such as psoriasis, or eczema. Subject who is currently or has received topical or systemic steroid medication therapy within the past four weeks affecting the course of the keloid and/or its evaluability. Inhaled steroid therapy is acceptable. Subject with the presence of acute infections in the areas intended for treatment. Subject with known hypersensitivity to bovine collagen or to the components of the Apligraf agarose shipping medium. Subject who is lactating or pregnant (positive result as determined by urine testing). Subject with liver (ALT/SGPT, ALP, AST/SGOT, bilirubin, albumin, total protein, LDH) and/or renal function (BUN and creatinine) tests > 2 x upper limit of normal (ULN). Subject who has been previously 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 the past three months. Subject previously treated with Apligraf, Dermagraft or any other cell therapy at the target keloid 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 with a history of anaphylaxis. 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
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: A<br>Apligraf (bilayered living cell therapy) | Device: Apligraf<br>* Application at Day 0, potential re-application at Week 4<br>|
| Active Comparator: B<br>Dressing regimen comprised of a primary nonadherent dressing, dry gauze dressing and bolster gauze dressing, if necessary | Other: Standard dressing regimen<br>* A primary nonadherent dressing, dry gauze dressing and bolster gauze dressing if necessary<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Summary of all reported adverse events (AE) in the intent to treat (ITT) population. AE was defined as any adverse change in the subject's medical status compared with the subject's baseline condition, whether or not the event was related to the study device or a study procedure; or an exacerbation (either in frequency or severity) in a subject's pre-existing condition. AE data were collected at every study visit or if volunteered by the subject at any time during the study. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Degree of Keloid Recurrence as Measured by Beausang Scar Scale (BSS) | Change in BSS cumulative score, Baseline to Last Visit, as reported by the Investigator, is reported. BSS is a composite score where the individual scores from the following categories are summed: Color (rated 1[perfect]-4[gross mismatch]), Shine (1/Matte or 2/Shiny), Contour (rated 1[flush with surrounding skin]-4[keloid]), Distortion (rated 1[None]-4[severe]), Texture (rated 1[normal]-4[hard]), and Overall Assessment on a 10cm visual analog scale (rated 0[excellent scar]-10 [poor scar]). Total score ranges from 5 (clinically well healed scar) - 28 (clinically poor scar). | Baseline to Week 52 or Last Visit | 
| Cumulative Incidence of Keloid Recurrence at Week 52 | Recurrence is defined the first study visit at which the Investigator scores the Contour component of the BSS with a 4 (indicating a keloid). Contour is one of the five components measured in the BSS with Contour scores ranging from 1 (flush with surrounding skin) to 4 (keloid). Recurrence is a negative outcome. | 52 weeks | 
| Degree of Recurrence (Scar Firmness) | Scar firmness measured by Cutometer in millimeters. | Week 52 or Last Visit | 
| Degree of Recurrence (Scar Thickness) | Scar thickness measured by slide caliper in millimeters. A value of 0.0 mm on the slide caliper is equivalent to normal, non-hypertrophic/raised skin. | Week 52 or Last visit | 
| Physician Global Assessment | Investigator assessed using 5 point scale (1-excellent, 2-very good, 3-good, 4-moderate, 5-poor) | Week 52 or Last Visit | 
| Subject Global Assessment | Subject assessed using 5 point scale (1-excellent, 2-very good, 3-good, 4-moderate, 5-poor) | Week 52 or Last Visit | 
| Decreased Utilization of Intralesional Steroid Intervention | The mean number of Intralesional (IL) Injections per participant is reported. A lower number of injections is a better outcome. | 52 weeks |