A Phase 2a Study to Evaluate the Safety and Efficacy of AZX100 in Trocar Sites of Arthroscopic Shoulder Surgery Patients

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 scars that were made from trocars following arthroscopic shoulder surgery.

Official Title
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A Phase 2a Double Blind, Placebo Within-Patient Controlled, Multi-Center Dose Ranging Study to Evaluate the Safety and Preliminary Efficacy of AZX100 Drug Product in Trocar Sites of Arthroscopic Shoulder Surgery Patients

Conditions
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Scar Prevention, Scar Reduction

Intervention / Treatment
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* Drug: Placebo
* Drug: AZX100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for an arthroscopic shoulder surgery that will result in at least 3 trocar sites Healthy male or non-pregnant female 18-75 years old Non-diabetic Body Mass Index 18-35 No clinically significant abnormal values on blood test Non-smoker for previous 6 months Exclusion Criteria: History of acute or chronic disease Cancer within previous 5 years, except for removed skin cancer Hypersensitivity reaction Allergy to general anesthesia, lidocaine, or epinephrine Current skin disorder other than folliculitis or acne On therapy with steroids On therapy with a drug that affects collagen synthesis Positive for HIV or hepatitis Positive urine test for nicotine Positive blood test for anti-AZX100 antibodies Participated in another clinical study within 60 days before enrollment Gave blood within 7 days before dosing Gave plasma within 3 days before dosing Tattoo on the shoulder area Applied any prescribed or over the counter agents to the shoulder within 14 days before dosing, or intend to use any scar improving product Visited a tanning salon within 14 days before dosing History of drug addiction or excessive use of alcohol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: AZX100-placebo<br>Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive one low dose of AZX100 3 mg/linear cm, one high dose of AZX100 10 mg/linear cm, or placebo (saline). | Drug: Placebo<br>* Patients in the Placebo-only arm were dosed intradermally with placebo (saline) in three trocar sites on Day 9 (plus/minus 2 days) and Day 21 (plus/minus 2 days) after arthroscopic shoulder surgery. In the AZX100-placebo arm, 3 or 10 mg or placebo (saline) was administered intradermally at each of three trocar sites on each patient 9 ± 2 days and 21 ± 2 days after arthroscopic surgery. The three trocar sites (anterior, lateral, and posterior sides of the shoulder) were randomized to receive the same dose of study agent for both dose administrations.<br>Drug: AZX100<br>* AZX100 Drug Product 3 or 10 mg or placebo (saline) was administered intradermally at each of three trocar sites on each patient 9 ± 2 days and 21 ± 2 days after arthroscopic surgery. The three trocar sites (anterior, lateral, and posterior sides of the shoulder) were randomized to receive the same dose of study agent for both dose administrations.<br>|
| Placebo Comparator: Placebo-only<br>Three trocar sites on each patient received one dose of placebo (saline). | Drug: Placebo<br>* Patients in the Placebo-only arm were dosed intradermally with placebo (saline) in three trocar sites on Day 9 (plus/minus 2 days) and Day 21 (plus/minus 2 days) after arthroscopic shoulder surgery. In the AZX100-placebo arm, 3 or 10 mg or placebo (saline) was administered intradermally at each of three trocar sites on each patient 9 ± 2 days and 21 ± 2 days after arthroscopic surgery. The three trocar sites (anterior, lateral, and posterior sides of the shoulder) were randomized to receive the same dose of study agent for both dose administrations.<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 and 3 mg AZX100, and placebo and 10 mg AZX100 12 months after shoulder surgery. Three trocar sites were randomized on each patient to receive AZX100 3 mg or AZX100 10 mg or placebo at 9 days and 21 days after shoulder surgery. PSAS results 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 results 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 Scores Rated by Independent Blinded Raters Using 3D Photography | Three trocar sites were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or saline placebo/cm at 9 days and 21 days after surgery. Twelve months after surgery, images of the trocar sites were longitudinally evaluated and rated using a standard 100 mm Visual Analog Scale (VAS) by two blinded independent dermatologists, with 0 being normal skin and 100 being the worst scar imaginable. Efficacy was based on the difference between VAS scores of placebo and 3 mg AZX100 and placebo and 10 mg AZX100 for each of the two raters separately. Data from both raters was not combined. | 12 months | 
| Between-group Mean Differences in Objective Measures Via 3D Photography (Elevation, Length, Width) | Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or placebo/cm at 9 days and 21 days following shoulder surgery. 3D digital photography of each trocar scar was used to calculate scar length, width, minimum elevation, and maximum elevation in millimeters (mm) at 12 months. The minimum elevation value was calculated as the lowest point of the scar below the interpolated smooth skin surface. This was always a negative number. Negative values (closer to zero) were more desirable. The maximum elevation value was the highest point of the scar above the interpolated smooth skin surface. A smaller value was preferred. | 12 months | 
| Between-group Mean Differences in Objective Measures Via 3D Photography (Volume) | Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm, or AZX100 10 mg/cm, or placebo/cm at 9 days and 21 days following shoulder surgery. 3D digital photography of each trocar scar was used to calculate positive volume, negative volume, and total volume in millimeters cubed (mm^3) at 12 months. Positive volume included the scar volume that was calculated to be above the interpolated smooth skin surface. A smaller value was preferred. Negative volume included the volume of the scar calculated to be below the interpolated smooth skin surface. It was always a negative number; negative values (closer to zero) were more desirable. Total volume was calculated as the sum of positive volume and the absolute value of negative volume. Smaller values were more desirable. | 12 months | 
| Histological Evaluation of Collagen | Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or placebo/cm at 9 days and 21 days following shoulder surgery. A skin punch biopsy was taken of each trocar site at 12 months. The specimens were blindly scored in duplicate by a dermal pathologist for dermal collagen fiber density, maturity and orientation, where 0% was completely normal and 100% was completely abnormal. | 12 months | 
| Histological Evaluation of Number of Alpha Smooth Muscle Actin Cells | Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or placebo/cm at 9 days and 21 days following shoulder surgery. A skin punch biopsy was taken of each trocar site at 12 months. For exploratory purposes, the specimens were blindly scored in duplicate by a dermal pathologist for the estimated number of alpha-smooth muscle actin (α-SMA) positive cells per high powered field. Values ranged from 0 to several hundred. The number of α-SMA cells was assessed for exploratory purposes; therefore, at the time of this report, it was not known whether it was better to have a low or high α-SMA score. | 12 months | 

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