Scar Prevention
Conditions
Keywords
Scarring
Brief summary
This study will compare how well EXC 001 works versus placebo in reducing the appearance of scars in subjects undergoing elective abdominoplasty. The study will also evaluate the safety of EXC 001 in healthy adult subjects.
Interventions
DRUGEXC 001
Intradermal injections of EXC 001 and placebo given on various schedules.
DRUGPlacebo
Intradermal injections of EXC 001 and placebo given on various schedules.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects must have sufficient excess abdominal tissue to qualify for a standard elective abdominoplasty * Subject has chosen to have an elective abdominoplasty * Medically healthy with normal screening results * Subjects must not be pregnant or lactating
Exclusion criteria
* Subjects with existing scars or significant striae on the abdominal pannus * Females who are currently pregnant or pregnant during the 12 months prior to inclusion in the study, or lactating * Participation in another clinical trial within 30 days prior to the start of the study * Any other condition or prior therapy, which, in the opinion of the PI, would make the subject unsuitable for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Expert Panel Scar Assessment Score | Week 13 of Part B | Scar assessment by an expert panel was done on blinded photographs using 100 millimeter (mm) visual analog scale (VAS) where a score of 0 mm = best possible scar and a score of 100 mm = worst possible scar, where higher scores indicate worse condition. The difference was calculated for scars at Week 13 as EXC 001 score minus placebo score, thus a negative difference would indicate that the EXC 001-treated scars had lower scar severity. The score was defined as the within participant average difference between EXC 001- and Placebo-treated scars at Week 13. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Part B: Day 1 up to Week 14 | Following vital sign parameters were assessed: diastolic blood pressure, systolic blood pressure, respiration rate, pulse rate, temperature and weight. Number of participants with clinically significant change in any vital sign parameter compared to Baseline were reported. Criteria for clinically significant change in any vital sign parameter compared to baseline was based on investigator's discretion. |
| Part B: Number of Participants With Clinically Significant Changes in Physical Examination Findings | Part B: Day 1 up to Week 14 | Physical examination included the assessment of skin; head, ears, eyes, nose, and throat; respiratory; cardiovascular; abdomen; musculoskeletal; neurological; gastrointestinal; genitourinary; endocrine and lymph nodes. Criteria for clinically significant findings in physical examination was based on investigator's discretion. |
| Part B: Physician Observer Global Assessment Scar Score | Week 13 of Part B | Physician observer global assessment of scar score was done using a valid published 10-point rating scale. Physicians rated severity of each scar on a scale of 1 = normal skin to 10 = worst scar imaginable. Each scar was given a single score and the differences in scores between the matched pairs of scars were calculated. There were 4 differences within each dose level that were averaged to create a single score for each participant at each dose level. The score was defined as the within participant average difference between EXC 001 and Placebo. |
| Part B: Number of Participants With Clinically Significant Abnormal Laboratory Findings | Part B: Day 1 up to Week 13 | Laboratory analysis included hematology, biochemistry and urinalysis. Hematology range: basophils (bas) 0-0.2, eosinophils (eos) 0-0.4, leukocytes (leu) 4-10.5, lymphocytes (lym) 0.7-4.5, neutrophils (neu) 1.8-7.8, platelet 140-415, monocytes (mon) 0.1-1 in 10\^9 per liter; bas/leu 0-3, eos/leu 0-7, lym/leu 14-46, mon/leu 4-13, neu/leu and neu/leu 40-74 in percentage, erythrocytes 3.8-5.1 10\^12/L, hematocrit 0.34-0.44 L/L, hemoglobin 115-150 gram per liter (g/L). Biochemistry range: creatine kinase 24-173, alkaline phosphatase 25-150, alanine aminotransferase (AT) and aspartate AT 0-40 in International units per liter; creatinine 50-88, urate 89-399, bilirubin 2-21 in micromole per liter, glucose 3.6-5.5, potassium 3.5-5.5, sodium 135-148, blood urea nitrogen 1.8-9.3 in millimole/L, albumin 35-55 g/L. Urinalysis parameters: pH (5-7.5), specific gravity (1.005-1.03). Participants with clinically significant abnormal change in any laboratory parameter compared to baseline were reported. |
| Part A and B: Number of Participants With Positive Skin Sensitivity Reaction | From Day 21 of Part A up to Week 2 of Part B | The skin sensitivity reaction was assessed only at the skin sensitivity reaction testing sites. Erythematous, raised (indurated) and edematous reactions were considered as positive skin sensitivity reactions. The number of participants that experienced any positive skin sensitivity reactions were reported. |
| Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | Week 13 of Part B | Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's correction (QTc), heart rate (HR). A standard, single 12-lead ECG was taken and results was classified as normal, having a clinically insignificant abnormality, or having a clinically significant abnormality. Number of participants with clinically significant abnormality in ECG compared to baseline were reported. Criteria for clinically significant abnormality in ECG compared to baseline was based on investigator's discretion. |
Countries
United States
Participant flow
Recruitment details
Participants who had chosen and qualified (had sufficient excess abdominal tissue) for a standard elective abdominoplasty were recruited in this study. The study was conducted in two-parts: Part A (Skin Testing Phase) and Part B (Active Dosing Phase). Participants with negative skin sensitization in Part A entered into Part B .
Pre-assignment details
Part B (incision wounds \[IW\] and abdominoplasty surgery): On Day 1, participants received 20 incisions (2 centimeters \[cm\] each), 10 incisions on either side of the midline (4 vertical columns of 4 incisions each, 2 columns of 2 incisions \[lateral biomarker incisions\]), on the abdominal area to be removed during abdominoplasty.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: EXC 001 and Placebo In Part A participants received single intradermal injections of EXC-001 at a dose of 5 mg on Day 1 and 21. Third 5 mg intradermal injection was administered at the discretion of Investigator based on the event of an equivocal skin sensitization on Day 38 or at least 7 days prior to surgery (Day 1 in Part B). The injection site was evaluated immediately after the injection and on Days 21, 28, 38, 50 until day of surgery. Participants with negative skin sensitization in Part A were assigned to Part B of the study. In Part B Participants received intradermal injections of EXC 001 on 1 side of the abdominal incisions and on the other side received intradermal injections of placebo matched to EXC 001 at Week 2, 4, 6, 8 and 10. On the EXC 001 treated side 1 column received high dose (5.0 mg/linear cm) and other a low dose (1.0 mg/linear cm). Out of 2 lateral biomarker incisions 1 incision received high dose (5.0 mg/linear cm) and other a low dose (1.0 mg/linear cm). Participants received an abdominoplasty at week 13 with a follow-up post-surgery visit at week 14. | 10 |
| Cohort 2: EXC 001 and Placebo In Part A participants received single intradermal injections of EXC-001 at a dose of 5 milligram (mg) on Day 1 and 21. Third 5 mg intradermal injection was administered at the discretion of Investigator based on the event of an equivocal skin sensitization on Day 38 or at least 7 days prior to surgery (Day 1 in Part B). The injection site was evaluated immediately after the injection and on Days 21, 28, 38, 50 until day of surgery. Participants with negative skin sensitization in Part A were assigned to Part B of the study. In Part B participants received intradermal injections of EXC 001 on 1 side of the abdominal incisions and on the other side received intradermal injections of placebo matched to EXC 001 at Week 2, 5, 8 and 11. On the EXC 001 treated side 1 column received high dose (5.0 mg/linear cm) and other a low dose (1.0 mg/linear cm). Out of 2 lateral biomarker incisions 1 incision received high dose (5.0 mg/linear cm) and other a low dose (1.0 mg/linear cm). Participants received an abdominoplasty at week 13 with a follow-up post-surgery visit at week 14. | 10 |
| Cohort 3: EXC 001 and Placebo In Part A participants received single intradermal injections of EXC-001 at a dose of 5 milligram (mg) on Day 1 and 21. Third 5 mg intradermal injection was administered at the discretion of Investigator based on the event of an equivocal skin sensitization on Day 38 or at least 7 days prior to surgery (Day 1 in Part B). The injection site was evaluated immediately after the injection and on Days 21, 28, 38, 50 until day of surgery. Participants with negative skin sensitization in Part A were assigned to Part B of the study. In Part B participants received intradermal injections of EXC 001 on 1 side of the abdominal incisions and on the other side received intradermal injections of placebo matched to EXC 001 at Week 2, 6 and 10. On the EXC 001 treated side 1 column received high dose (5.0 mg/linear cm) and other a low dose (1.0 mg/linear cm). Out of 2 lateral biomarker incisions 1 incision received high dose (5.0 mg/linear cm) and other a low dose (1.0 mg/linear cm). Participants received an abdominoplasty at week 13 with a follow-up post-surgery visit at week 14. | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A: Skin Testing Phase (50 Days) | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: EXC 001 and Placebo | Cohort 2: EXC 001 and Placebo | Cohort 3: EXC 001 and Placebo | 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 | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 10 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 10 | 2 / 10 | 1 / 10 | 9 / 9 | 8 / 10 | 8 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 9 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Part B: Expert Panel Scar Assessment Score
Scar assessment by an expert panel was done on blinded photographs using 100 millimeter (mm) visual analog scale (VAS) where a score of 0 mm = best possible scar and a score of 100 mm = worst possible scar, where higher scores indicate worse condition. The difference was calculated for scars at Week 13 as EXC 001 score minus placebo score, thus a negative difference would indicate that the EXC 001-treated scars had lower scar severity. The score was defined as the within participant average difference between EXC 001- and Placebo-treated scars at Week 13.
Time frame: Week 13 of Part B
Population: Completer population included all participants who missed not more than 1 dose of study drug, had the Week 13 assessment and non-missing data for VAS scar assessment score for at least one dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Cohort 1: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Expert Panel Scar Assessment Score | -3.16 millimeters | Standard Deviation 7.687 |
| Part B: Cohort 1: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Expert Panel Scar Assessment Score | 0.18 millimeters | Standard Deviation 7.154 |
| Part B: Cohort 2: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Expert Panel Scar Assessment Score | 1.45 millimeters | Standard Deviation 12.45 |
| Part B: Cohort 2: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Expert Panel Scar Assessment Score | 2.91 millimeters | Standard Deviation 9.778 |
| Part B: Cohort 3: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Expert Panel Scar Assessment Score | -4.78 millimeters | Standard Deviation 11.326 |
| Part B: Cohort 3: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Expert Panel Scar Assessment Score | -4.05 millimeters | Standard Deviation 8.934 |
Secondary
Part A and B: Number of Participants With Positive Skin Sensitivity Reaction
The skin sensitivity reaction was assessed only at the skin sensitivity reaction testing sites. Erythematous, raised (indurated) and edematous reactions were considered as positive skin sensitivity reactions. The number of participants that experienced any positive skin sensitivity reactions were reported.
Time frame: From Day 21 of Part A up to Week 2 of Part B
Population: Safety population included participants who completed Part A Day 1 visit and received at least 1 dose of study drug. Safety assessment was not planned separately for EXC 001 and placebo in Part B. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B: Cohort 1: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part A and B: Number of Participants With Positive Skin Sensitivity Reaction | 0 Participants |
| Part B: Cohort 1: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part A and B: Number of Participants With Positive Skin Sensitivity Reaction | 0 Participants |
| Part B: Cohort 2: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part A and B: Number of Participants With Positive Skin Sensitivity Reaction | 0 Participants |
Secondary
Part B: Number of Participants With Clinically Significant Abnormal Laboratory Findings
Laboratory analysis included hematology, biochemistry and urinalysis. Hematology range: basophils (bas) 0-0.2, eosinophils (eos) 0-0.4, leukocytes (leu) 4-10.5, lymphocytes (lym) 0.7-4.5, neutrophils (neu) 1.8-7.8, platelet 140-415, monocytes (mon) 0.1-1 in 10\^9 per liter; bas/leu 0-3, eos/leu 0-7, lym/leu 14-46, mon/leu 4-13, neu/leu and neu/leu 40-74 in percentage, erythrocytes 3.8-5.1 10\^12/L, hematocrit 0.34-0.44 L/L, hemoglobin 115-150 gram per liter (g/L). Biochemistry range: creatine kinase 24-173, alkaline phosphatase 25-150, alanine aminotransferase (AT) and aspartate AT 0-40 in International units per liter; creatinine 50-88, urate 89-399, bilirubin 2-21 in micromole per liter, glucose 3.6-5.5, potassium 3.5-5.5, sodium 135-148, blood urea nitrogen 1.8-9.3 in millimole/L, albumin 35-55 g/L. Urinalysis parameters: pH (5-7.5), specific gravity (1.005-1.03). Participants with clinically significant abnormal change in any laboratory parameter compared to baseline were reported.
Time frame: Part B: Day 1 up to Week 13
Population: Safety population included participants who completed Part A Day 1 visit and received at least 1 dose of study drug. Safety assessment was not planned separately for EXC 001 and placebo in Part B. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B: Cohort 1: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Abnormal Laboratory Findings | 0 Participants |
| Part B: Cohort 1: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Abnormal Laboratory Findings | 0 Participants |
| Part B: Cohort 2: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Abnormal Laboratory Findings | 0 Participants |
Secondary
Part B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Following vital sign parameters were assessed: diastolic blood pressure, systolic blood pressure, respiration rate, pulse rate, temperature and weight. Number of participants with clinically significant change in any vital sign parameter compared to Baseline were reported. Criteria for clinically significant change in any vital sign parameter compared to baseline was based on investigator's discretion.
Time frame: Part B: Day 1 up to Week 14
Population: Safety population included participants who completed Part A Day 1 visit of and received at least 1 dose of study drug. Safety assessment was not planned separately for EXC 001 and placebo in Part B. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B: Cohort 1: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Part B: Cohort 1: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Part B: Cohort 2: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Secondary
Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings
Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's correction (QTc), heart rate (HR). A standard, single 12-lead ECG was taken and results was classified as normal, having a clinically insignificant abnormality, or having a clinically significant abnormality. Number of participants with clinically significant abnormality in ECG compared to baseline were reported. Criteria for clinically significant abnormality in ECG compared to baseline was based on investigator's discretion.
Time frame: Week 13 of Part B
Population: Safety population included participants who completed Part A Day 1 visit of and received at least 1 dose of study drug. Safety assessment was not planned separately for EXC 001 and placebo in Part B. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B: Cohort 1: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part B: Cohort 1: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part B: Cohort 2: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Part B: Number of Participants With Clinically Significant Changes in Physical Examination Findings
Physical examination included the assessment of skin; head, ears, eyes, nose, and throat; respiratory; cardiovascular; abdomen; musculoskeletal; neurological; gastrointestinal; genitourinary; endocrine and lymph nodes. Criteria for clinically significant findings in physical examination was based on investigator's discretion.
Time frame: Part B: Day 1 up to Week 14
Population: Safety population included participants who completed Part A Day 1 visit of Part A and received at least 1 dose of study drug. Safety assessment was not planned separately for EXC 001 and placebo in Part B. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B: Cohort 1: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Changes in Physical Examination Findings | 1 Participants |
| Part B: Cohort 1: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Changes in Physical Examination Findings | 0 Participants |
| Part B: Cohort 2: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Number of Participants With Clinically Significant Changes in Physical Examination Findings | 1 Participants |
Secondary
Part B: Physician Observer Global Assessment Scar Score
Physician observer global assessment of scar score was done using a valid published 10-point rating scale. Physicians rated severity of each scar on a scale of 1 = normal skin to 10 = worst scar imaginable. Each scar was given a single score and the differences in scores between the matched pairs of scars were calculated. There were 4 differences within each dose level that were averaged to create a single score for each participant at each dose level. The score was defined as the within participant average difference between EXC 001 and Placebo.
Time frame: Week 13 of Part B
Population: Completer population included all participants who missed not more than 1 dose of study drug, had the Week 13 assessment and non-missing data for VAS scar assessment score for at least one dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Cohort 1: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Physician Observer Global Assessment Scar Score | -0.84 units on a scale | Standard Deviation 1.362 |
| Part B: Cohort 1: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Physician Observer Global Assessment Scar Score | -0.44 units on a scale | Standard Deviation 1.193 |
| Part B: Cohort 2: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Physician Observer Global Assessment Scar Score | -0.68 units on a scale | Standard Deviation 1.448 |
| Part B: Cohort 2: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Physician Observer Global Assessment Scar Score | -0.05 units on a scale | Standard Deviation 0.848 |
| Part B: Cohort 3: EXC 001 High Dose (5.0 mg/Linear cm) + Placebo | Part B: Physician Observer Global Assessment Scar Score | -0.75 units on a scale | Standard Deviation 1.965 |
| Part B: Cohort 3: EXC 001 Low Dose (1.0 mg/Linear cm) + Placebo | Part B: Physician Observer Global Assessment Scar Score | -0.70 units on a scale | Standard Deviation 1.153 |