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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Company, Inc.
  • Texas
    • Austin, Texas, United States, 78759
      • Dermresearch, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• keloid scar between 1 and 3 cm long, less than 1 cm at its widest point
• willing to undergo keloid scar removal 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 malignant neoplasm within the last 5 years, except for surgically removed cancers of the skin that are not on the keloid area
• history of anaphylactic shock or anaphylactoid (hypersensitivity) reaction
• allergy to local anesthesia, including lidocaine and epinephrine
• ongoing 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
• donate blood within 7 days before dosing with study drug
• donate plasma within 3 days before dosing with study drug
• have a tattoo within 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 a tanning bed or tanning light within 3 months before enrollment
• intend to use any scar improving product during the study (one year)
• history of drug addiction or excessive use of alcohol
• previous drug treatment of the keloid scar that will be removed within the last 3 years; any laser, irradiation, or surgery of the keloid scar that will be removed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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.
Experimental: High Dose	Drug: AZX100 Drug Product; Subjects were administered AZX100 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.; Drug: AZX100 Drug Product; 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.
Experimental: Low Dose	Drug: AZX100 Drug Product; Subjects were administered AZX100 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.; Drug: AZX100 Drug Product; 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.

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, 3 mg AZX100, and 10 mg AZX100 12 months after surgery. This gave four comparisons to placebo: patient or observer and 3 mg and 10 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 millimeters (mm), with 0 being normal skin and 100 being the worst scar imaginable. The scars were presented in longitudinal (chronological) order. 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 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 scar measurements based on 3D photography of the scar surface at Month 12 and included maximum length, maximum width perpendicular to 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 smooth 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 smooth interpolated skin surface, and was always a negative number. Total volume was calculated as the sum of positive volume and the absolute value of negative volume. Smaller values were more desirable.	12 months

Collaborators and Investigators

• Sponsor: Capstone Therapeutics

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: January 20, 2009
• First Submitted That Met QC Criteria: January 20, 2009
• First Posted (Estimate): January 21, 2009

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; Keloid; Visual Analog Scale; Scarring; Scar prevention; POSAS; AZX100; Patient and Observer Scar Assessment Scale; Scar reduction
• Additional Relevant MeSH Terms: Pathologic Processes; Connective Tissue Diseases; Fibrosis; Cicatrix; Collagen Diseases; Keloid
• Other Study ID Numbers: OL-ASCAR-04