Scar Prevention, Scar Reduction
Conditions
Keywords
AZX100, Patient and Observer Scar Assessment Scale, POSAS, Visual Analog Scale, VAS, Keloid, Scarring, Scar reduction, Scar prevention
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 re-growth of surgically removed keloid scars.
Interventions
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.
DRUGPlacebo
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.
Sponsors
Capstone Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | 12 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | 12 Months | 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. |
| Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 12 Months | 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. |
| Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | 12 months | 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. |
Countries
United States
Participant flow
Recruitment details
Enrollment in the study began in June 2009 and was completed in September 2010. All patients were enrolled in dermatological medical clinics.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose AZX100 Drug Product 0.3 mg was administered intradermally per linear centimeter along the excision line following keloid scar excision at 21 days and 42 days after surgery. | 21 |
| High Dose AZX100 Drug Product 1 mg was administered intradermally per linear centimeter along the excision line following keloid scar excision at 21 days and 42 days after surgery. | 19 |
| Placebo Placebo (0.9% saline) was administered intradermally per linear centimeter along the excision line following keloid scar excision at 21 days and 42 days after surgery. | 19 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | High Dose | Placebo | Low Dose | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 19 Participants | 21 Participants | 59 Participants |
| Age Continuous | 36.1 years STANDARD_DEVIATION 10.9 | 37.5 years STANDARD_DEVIATION 12.4 | 37.1 years STANDARD_DEVIATION 11 | 36.9 years STANDARD_DEVIATION 11.2 |
| Region of Enrollment United States | 19 participants | 19 participants | 21 participants | 59 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 10 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 21 | 17 / 19 | 18 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 19 | 0 / 19 |
Outcome results
Primary
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.
Time frame: 12 Months
Population: In this early phase study, the efficacy and safety analyses were performed using an evaluable subject sample, which included all subjects who received study agent and provided some efficacy or safety data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PSAS Results for Placebo | Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | 23.29 Units on a scale | Standard Deviation 15.06 |
| PSAS Results for 0.3 mg AZX100 | Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | 24.11 Units on a scale | Standard Deviation 14.75 |
| PSAS Results for 1 mg AZX100 | Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | 21.33 Units on a scale | Standard Deviation 11.36 |
| OSAS Results for Placebo | Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | 18.53 Units on a scale | Standard Deviation 10.07 |
| OSAS Results for 0.3 mg AZX100 | Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | 23.47 Units on a scale | Standard Deviation 8.78 |
| OSAS Results for 1 mg AZX100 | Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores | 18.33 Units on a scale | Standard Deviation 10 |
p-value: 0.87Wilcoxon (rank sum)
p-value: 0.86Wilcoxon (rank sum)
p-value: 0.11Wilcoxon (rank sum)
p-value: 0.91Wilcoxon (rank sum)
Secondary
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.
Time frame: 12 Months
Population: In this early phase study, the efficacy and safety analyses were performed using an evaluable subject sample, which included all subjects who received study agent and provided some efficacy or safety data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PSAS Results for Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 27.71 Millimeters | Standard Deviation 6.76 |
| PSAS Results for 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 27.90 Millimeters | Standard Deviation 7.67 |
| PSAS Results for 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 27.51 Millimeters | Standard Deviation 5.63 |
| OSAS Results for Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 13.48 Millimeters | Standard Deviation 4.82 |
| OSAS Results for 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 15.67 Millimeters | Standard Deviation 5.03 |
| OSAS Results for 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 12.52 Millimeters | Standard Deviation 4.28 |
| Scar Minimum Elevation - Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | -0.86 Millimeters | Standard Deviation 1.09 |
| Scar Minimum Elevation - 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | -0.57 Millimeters | Standard Deviation 0.62 |
| Scar Minimum Elevation - 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | -0.38 Millimeters | Standard Deviation 0.12 |
| Scar Maximum Elevation - Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 2.01 Millimeters | Standard Deviation 1.2 |
| Scar Maximum Elevation - 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 2.44 Millimeters | Standard Deviation 1.36 |
| Scar Maximum Elevation - 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 1.74 Millimeters | Standard Deviation 0.92 |
| Scar Mean Elevation - Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 0.40 Millimeters | Standard Deviation 0.4 |
| Scar Mean Elevation - 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 0.51 Millimeters | Standard Deviation 0.34 |
| Scar Mean Elevation - 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Elevation, Length, Width) | 0.31 Millimeters | Standard Deviation 0.25 |
p-value: 0.73Wilcoxon (rank sum)
p-value: 0.94Wilcoxon (rank sum)
p-value: 0.14Wilcoxon (rank sum)
p-value: 0.68Wilcoxon (rank sum)
p-value: 0.56Wilcoxon (rank sum)
p-value: 0.32Wilcoxon (rank sum)
p-value: 0.33Wilcoxon (rank sum)
p-value: 0.65Wilcoxon (rank sum)
p-value: 0.21Wilcoxon (rank sum)
p-value: 0.9Wilcoxon (rank sum)
Secondary
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.
Time frame: 12 months
Population: In this early phase study, the efficacy and safety analyses were performed using an evaluable subject sample, which included all subjects who received study agent and provided some efficacy or safety data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PSAS Results for Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | 0.42 Millimeters cubed | Standard Deviation 0.39 |
| PSAS Results for 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | 0.65 Millimeters cubed | Standard Deviation 0.49 |
| PSAS Results for 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | 0.37 Millimeters cubed | Standard Deviation 0.25 |
| OSAS Results for Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | -0.04 Millimeters cubed | Standard Deviation 0.06 |
| OSAS Results for 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | -0.06 Millimeters cubed | Standard Deviation 0.07 |
| OSAS Results for 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | -0.06 Millimeters cubed | Standard Deviation 0.05 |
| Scar Minimum Elevation - Placebo | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | 0.45 Millimeters cubed | Standard Deviation 0.39 |
| Scar Minimum Elevation - 0.3 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | 0.71 Millimeters cubed | Standard Deviation 0.53 |
| Scar Minimum Elevation - 1 mg AZX100 | Between-group Mean Differences in Objective Measures Obtained Via 3D Photography (Volume) | 0.43 Millimeters cubed | Standard Deviation 0.23 |
p-value: 0.16Wilcoxon (signed rank)
p-value: 0.74Wilcoxon (signed rank)
p-value: 0.45Wilcoxon (signed rank)
p-value: 0.079Wilcoxon (signed rank)
p-value: 0.16Wilcoxon (signed rank)
p-value: 0.45Wilcoxon (signed rank)
Secondary
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.
Time frame: 12 Months
Population: In this early phase study, the efficacy and safety analyses were performed using an evaluable subject sample, which included all subjects who received study agent and provided some efficacy or safety data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PSAS Results for Placebo | Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | 71.9 Millimeters | Standard Deviation 21.2 |
| PSAS Results for 0.3 mg AZX100 | Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | 77.0 Millimeters | Standard Deviation 20.3 |
| PSAS Results for 1 mg AZX100 | Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | 68.1 Millimeters | Standard Deviation 23.3 |
| OSAS Results for Placebo | Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | 56.1 Millimeters | Standard Deviation 12.8 |
| OSAS Results for 0.3 mg AZX100 | Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | 62.2 Millimeters | Standard Deviation 10.9 |
| OSAS Results for 1 mg AZX100 | Between-group Mean Differences in Visual Analog Scale (VAS) Scores by Independent Blinded Raters | 54.3 Millimeters | Standard Deviation 13.2 |
p-value: 0.23Wilcoxon (rank sum)
p-value: 0.82Wilcoxon (rank sum)
p-value: 0.23Wilcoxon (rank sum)
p-value: 0.71Wilcoxon (rank sum)