A Phase 2a Study to Evaluate the Safety and Efficacy of AZX100 in Trocar Sites of Arthroscopic Shoulder Surgery Patients
Primary Purpose
Scar Prevention, Scar Reduction
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
AZX100
Sponsored by
About this trial
This is an interventional prevention trial for Scar Prevention focused on measuring AZX100, Patient and Observer Scar Assessment Scale, POSAS, Visual Analog Scale, VAS, Trocar, Scarring, Scar reduction, Scar prevention
Eligibility Criteria
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
Sites / Locations
- Lotus Clinical Research, Inc.
- Florida Research Associates
- Atlas Orthopedics & Sports Medicine
- Orthopaedics East, PA
- Texas Orthopedics, Sports & Rehab Assoc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZX100-placebo
Placebo-only
Arm Description
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).
Three trocar sites on each patient received one dose of placebo (saline).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT00811577
First Posted
December 18, 2008
Last Updated
September 10, 2012
Sponsor
Capstone Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT00811577
Brief Title
A Phase 2a Study to Evaluate the Safety and Efficacy of AZX100 in Trocar Sites of Arthroscopic Shoulder Surgery Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Capstone Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Scar Prevention, Scar Reduction
Keywords
AZX100, Patient and Observer Scar Assessment Scale, POSAS, Visual Analog Scale, VAS, Trocar, Scarring, Scar reduction, Scar prevention
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZX100-placebo
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo-only
Arm Type
Placebo Comparator
Arm Description
Three trocar sites on each patient received one dose of placebo (saline).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
AZX100
Intervention Description
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.
Primary Outcome Measure Information:
Title
Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Between-group Mean Differences in Visual Analog Scale Scores Rated by Independent Blinded Raters Using 3D Photography
Description
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.
Time Frame
12 months
Title
Between-group Mean Differences in Objective Measures Via 3D Photography (Elevation, Length, Width)
Description
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.
Time Frame
12 months
Title
Between-group Mean Differences in Objective Measures Via 3D Photography (Volume)
Description
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.
Time Frame
12 months
Title
Histological Evaluation of Collagen
Description
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.
Time Frame
12 months
Title
Histological Evaluation of Number of Alpha Smooth Muscle Actin Cells
Description
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.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Lotus Clinical Research, Inc.
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Florida Research Associates
City
Deland
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Atlas Orthopedics & Sports Medicine
City
Orlando
State/Province
Florida
ZIP/Postal Code
32822
Country
United States
Facility Name
Orthopaedics East, PA
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Texas Orthopedics, Sports & Rehab Assoc.
City
Austin
State/Province
Texas
ZIP/Postal Code
78759
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 2a Study to Evaluate the Safety and Efficacy of AZX100 in Trocar Sites of Arthroscopic Shoulder Surgery Patients
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