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

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

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.

Study Overview

• Status: Completed
• Conditions: Scar Prevention; Scar Reduction
• Intervention / Treatment: Drug: Placebo; Drug: AZX100

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research, Inc.
  • Florida
    • Deland, Florida, United States, 32720
      • Florida Research Associates
    • Orlando, Florida, United States, 32822
      • Atlas Orthopedics & Sports Medicine
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Orthopaedics East, PA
  • Texas
    • Austin, Texas, United States, 78759
      • Texas Orthopedics, Sports & Rehab Assoc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AZX100-placebo; 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; 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.; Drug: AZX100; 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.
PLACEBO_COMPARATOR: Placebo-only; Three trocar sites on each patient received one dose of placebo (saline).	Drug: Placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Capstone Therapeutics

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: December 18, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (ESTIMATE): December 19, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): October 11, 2012
• Last Update Submitted That Met QC Criteria: September 10, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: VAS; Visual Analog Scale; Scarring; Scar prevention; Trocar; POSAS; AZX100; Patient and Observer Scar Assessment Scale; Scar reduction
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix
• Other Study ID Numbers: OL-ASCAR-03