A Study to Evaluate the Safety and Efficacy of Additional Doses of AZX100 Drug Product Following Excision of Keloid Scars

Study Overview
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Brief Summary
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The purpose of this study was to determine the safety of AZX100 Drug Product and to determine whether it was effective in preventing or reducing re-growth of surgically removed keloid scars.

Official Title
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A Pilot Phase 2a Blinded, Placebo Controlled, Multicenter Parallel Group, Dose Ranging Study to Evaluate the Safety and Preliminary Efficacy of Additional Doses of AZX100 Drug Product Following Excision of Keloids

Conditions
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Scar Prevention, Scar Reduction

Intervention / Treatment
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* Drug: AZX100 Drug Product
* Drug: Placebo
* Drug: AZX100 Drug Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Keloid scar located below the neck between 1 and 3 cm long and less than 1 cm at its widest point Willing to undergo keloid scar excision surgery Healthy adult male or non-pregnant female Non-diabetic Body Mass Index in the range of 18-35 No clinically significant abnormal values on a full blood safety screen Non-smoker and non-nicotine user for the previous six months Exclusion Criteria: History or clinical evidence of acute or chronic disease History of cancer within the last 5 years, except for surgically removed cancers of the skin that are not near the keloid area History of anaphylactic shock or anaphylactoid (hypersensitivity) reaction Allergy to local anesthesia, including lidocaine and epinephrine Dermatologic disorders, except for folliculitis and acne On therapy with steroids On therapy with a drug that would affect collagen synthesis Positive urine test for nicotine or drugs of abuse Positive blood test for HIV 1 or 2, hepatitis B or hepatitis C Positive blood test for anti-AZX100 antibodies Participation in another study within 60 days prior to enrollment Blood donation within 7 days before dosing with study drug Plasma donation within 3 days before dosing with study drug Tattoo within approximately 3 cm of the keloid scar that will be removed Apply any lotion or cream on or near the keloid scar that will be removed within 14 days before dosing with study drug Use of a tanning bed or tanning light within the 3 months before enrollment Intend to use any scar improving product during of the study (1 year) History of drug addiction or excessive use of alcohol Previous drug treatment of the keloid scar within the last 3 years, or have had any laser, irradiation, or surgical treatment of the keloid scar that will be removed

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br> | Drug: AZX100 Drug Product<br>* Subjects were administered AZX100 0.3 mg per linear centimeter (low dose) intradermally at the site of the keloid scar removal. The first dose was given 19-23 days following surgery, and the second dose was given 40-44 days following surgery.<br>|
| Experimental: High Dose<br> | Drug: AZX100 Drug Product<br>* Subjects were administered AZX100 10 mg per linear centimeter (high dose) intradermally at the site of the keloid scar removal. The first dose was given 19-23 days following surgery, and the second dose was given 40-44 days following surgery.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subjects were administered placebo (0.9% saline) per linear centimeter intradermally at the site of the keloid scar removal. The first dose was given 19-23 days following surgery, and the second dose was given 40-44 days following surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | Efficacy was based on the difference between mean POSAS scores of placebo, 0.3 mg AZX100, and 1 mg AZX100 12 months after surgery. This gave four comparisons to placebo: patient or observer and 0.3 mg and 1 mg AZX100. PSAS included patients' ratings on a scale of 1-10 (1 was normal skin or no complaints and 10 was the worst imaginable scar or the worst difference) for the following: Is the scar painful? Is the scar itching? Is the color of the scar different? Is the scar more stiff? Is the thickness of the scar different? Is the scar irregular? The possible minimum score was 6 and the maximum (worst) score was 60. OSAS included observers' ratings on a scale of 1-10 (1 was normal skin and 10 was the worst scar imaginable) for vascularization, pigmentation, thickness, relief, and pliability. The possible minimum score was 5 and the possible maximum (worst) score was 50. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | At 12 months, two independent dermatologists who were blinded to study treatment evaluated the scar images using a Visual Analog Scale (VAS) of 0-100 mm, with 0 being normal skin and 100 being the worst scar imaginable. The scars were presented in a scrambled order. Efficacy was based on the difference between VAS scores of placebo and 0.3 mg AZX100, and placebo and 1 mg AZX100, for each of the two raters separately. Data from the two raters was not combined. | 12 Months | 
| Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | This secondary outcome included measurements based on 3D photography of the scar surface at Month 12 and included maximum length, maximum width perpendicular to the maximum length, and minimum, maximum and mean elevation. All elevation measurements were made relative to the interpolated smooth skin surface. A value closest to zero was preferred, because zero was equal to the normal skin surface. The minimum elevation value was calculated as the lowest point of the scar below the interpolated smoooth skin surface and was always a negative number. A more negative number was worse, because it indicated a deeper measurement below the interpolated smooth skin surface. The maximum elevation value was calculated as the highest point of the scar above the interpolated smooth skin surface. A larger number was worse because it indicated a higher peak above the interpolated smooth skin surface. The mean elevation of the scar relative to the interpolated smooth skin surface was also calculated. | 12 Months | 
| Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | This secondary outcome included measurements based on 3D photography of the scar surface at Month 12 and included positive volume, negative volume and total volume. All volume measurements were made relative to the interpolated smooth skin surface. A value closer to zero was preferred, because zero was equal to the normal skin surface. Positive volume was calculated as the volume of the scar above the interpolated smooth skin surface. Negative volume was calculated as the volume of the scar below the interpolated smooth skin surface, and was always a negative number. Total volume was calculated as the sum of the positive volume and the absolute value of the negative volume. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scar reduction, AZX100, Patient and Observer Scar Assessment Scale, POSAS, Visual Analog Scale, VAS, Keloid, Scarring, Scar prevention