Juvista in Scar Revision Surgery of Disfiguring Scars

Study Overview
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Brief Summary
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This trial is to determine whether Juvista can prevent scar formation or improve the appearance of scars following scar revision surgery. The trial will involve comparing Juvista to placebo.

Detailed Description
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Each year, over one hundred million people undergo elective or emergency surgery and are left with scarring. Of these, over half a million patients undergo scar revision surgery. These types of scars are usually disfiguring, aesthetically unpleasant and can cause complications such as severe itching, tenderness, pain, depression and disruption of daily activities which can lead to a diminished quality of life. There is a clinical need for treatments that reduce scarring, as current therapies are often ineffective or inadequate. Results from previous clinical trials show that Juvista is effective in improving scars in young and elderly males and females. Juvista-treated wounds appear to heal with scars that are more similar to the surrounding skin, and are narrower and paler with a faster fading of redness compared to placebo and standard care alone. This study will confirm the effectiveness of Juvista (avotermin) in the improvement of scar appearance when applied to the wound margins of patients following scar revision surgery of disfiguring scars. The study is a double blind, within patient, placebo controlled, randomised trial in male and female patients. Patients will be asked to attend 10 study visits and will be followed up post-surgery for 12 months. The potential benefits to the patients taking part in the trial will be that their scar is revised by a plastic surgeon. This procedure should leave subjects with a less noticeable scar. The existing scar will be surgically removed and the resulting wound will be divided into two segments of equal length. In most patients, one segment will receive treatment with Juvista administered by intradermal injection, the other with placebo. A few patients will receive treatment with Juvista to both segments of the wound.

Official Title
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A Double Blind, Within Patient, Placebo Controlled Trial to Assess the Efficacy of Juvista (Avotermin) in Conjunction With Scar Revision Surgery for the Improvement of Disfiguring Scars.

Conditions
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Cicatrix

Intervention / Treatment
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* Drug: Juvista (avotermin)
* Drug: Juvista (avotermin)
* Drug: Juvista (avotermin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-85 years who have provided written informed consent. BMI between 15 and 35 kg/m2 Patients with, in the opinion of the Investigator, clinically acceptable results for the laboratory tests specified in the trial protocol. If females of child bearing potential, patients must be using a highly effective method(s) of contraception and agree to do so from at least the screening visit until one month after administration of the final study dose. The scar area to be revised is disfiguring. To be considered disfiguring for this trial scars must have at least one of the following characteristics. Scar area 13 or more cm in length. Scar area at least 0.6 cm wide at widest part. Surface contour of scar area elevated or depressed on palpation. Scar area adherent to underlying tissue. Skin hypo-or hyper-pigmented in an area exceeding 39cm2. Skin texture abnormal (irregular, atrophic, shiny, scaly, etc.) in an area exceeding 39cm2. The scar to be revised is at least 12 months old. The investigator considers that the appearance of the scar area to be revised can be improved with surgery alone. The scar area is linear and suitable for revision by excision and direct closure. The scar area to be revised is symmetrical in appearance around the mid-line. The scar area to be revised is between 7 and 20cm in length. The scar area to be revised runs along a flat surface which is in the same focal plane and suitable for accurate medical photography. The scar is approved for entry into the trial by the Independent Expert Screening Panel. Exclusion Criteria Patients who on direct questioning and / or physical examination, have evidence of any past or present clinically significant medical condition that would impair wound healing. Patients with a creatinine clearance (CLcr) of 80ml/min or less. Creatinine clearance will be determined from the serum creatinine level at pre-study screening using the following formula : CLcr = (140-age (years)) x weight(kg)/ 72 x serum creatinine (mg/dL) {x 0.85 for females} Patients with a skin disorder that is chronic or currently active. Patients who, in the opinion of the Investigator, have significant ongoing psychiatric disorders, which may interfere with the trial assessments / visits. Patients with a history of clinically significant hypersensitivity to any of the drugs or surgical dressings to be used in this trial. Patients who are taking, or have taken, any investigational drugs within 3 months prior to the screening visit. Patients undergoing investigations or changes in management for an existing medical condition (excluding the scar for revision). Patients who are or who become pregnant up to and including Day 0 or who are lactating. In the opinion of the Investigator, a patient who is not likely to complete the trial. Patients who on direct questioning and physical examination have history or evidence of keloid scarring. Patients with scar areas for revision that cross a joint or are in close proximity to an anatomical structure, which could lead to distortion of the resultant scar or difficulty in taking photographs. Patients with additional scars less than 3cm away from the area to be revised. Patients with scars that require revision using Z-plasty, W-plasty or any other such techniques. Patients who are involved in ongoing litigation in connection with the scar to be revised. Patients who have had surgery in the area to be excised within one year of Day 0.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Active versus Placebo within patient | Drug: Juvista (avotermin)<br>* 100ng/100µL Juvista administered to each linear centimetre of the margins of one wound segment by intradermal injection immediately after and then 24h after wound closure versus 100μL of placebo administered to each linear centimetre of the margins of the other wound segment by intradermal injection immediately after and then 24h after wound closure<br>* Other names: RN1001, TGFβ3;|
| Other: 2<br>Active vs. Placebo within patient | Drug: Juvista (avotermin)<br>* 250ng/100µL Juvista administered to each linear centimetre of the margins of one wound segment by intradermal injection immediately after and then 24h after wound closure versus 100μL of placebo administered to each linear centimetre of the margins of the other wound segment by intradermal injection immediately after and then 24h after wound closure<br>* Other names: RN1001, TGFβ3;|
| Other: 3<br>Active vs. Active within patient | Drug: Juvista (avotermin)<br>* 250ng/100µL Juvista administered to each linear centimetre of the margins of both wound segments by intradermal injection immediately after and then 24h after wound closure<br>* Other names: RN1001, TGFβ3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Scar Comparison Scale as assessed by an Independent Clinical Scar Assessment Panel using photographs of the treated scars. |  | 12 months post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Scar Comparison Scale assessed by the patient looking at their own scars. |  | 12 months post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scar Revision