Keloid
Conditions
Brief summary
This pilot study will assess the safety and efficacy of Apligraf in the healing and recurrence of keloids post surgical shave excision in patients with clinically diagnosed keloids.
Interventions
DEVICEApligraf
Application at Day 0, potential re-application at Week 4
A primary nonadherent dressing, dry gauze dressing and bolster gauze dressing if necessary
Sponsors
Organogenesis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject is between 18 and 65 years of age. * Subject or legal guardian has read, understood, and signed appropriate Institutional Review Board (IRB) approved informed consent, photography release form and HIPAA consent in their own language. * Subject with 1 keloid measuring between 1 cm2 - 40 cm2 as assessed by the Investigator, present for at least 6 months and a Beausang Scar scale combined score of 5 or greater. * Subject is a male or female who must have a documented negative urine pregnancy test if of child bearing potential. Sexually active females must be practicing a medically proven form of contraception during the course of the study period. * Subject and/or legal guardian must be able and willing to follow study procedures and instructions. * Subject and/or legal guardian must be able and willing to return for follow-up study visits. * Subject agrees to not use a keloid medication or injection treatment for four weeks prior to Day 0. * Subject agrees not to use any other keloid treatments for the duration of the study. * Subject is otherwise healthy as assessed and determined by the Investigator
Exclusion criteria
* Subject is suffering from a condition likely to require medical attention, including administration of any treatment which in the opinion of the Investigator could influence the results of the study. * Subject with any systemic condition like uncontrolled diabetes mellitus (glycosylated hemoglobin, HbA1C \> 10%), cancer (biopsy confirming active malignancy), positive HIV test, or any disorder(s) that may compromise wound healing. * Subject is suffering from an abnormal skin condition on the affected area not usually associated with keloids such as psoriasis, or eczema. * Subject who is currently or has received topical or systemic steroid medication therapy within the past four weeks affecting the course of the keloid and/or its evaluability. Inhaled steroid therapy is acceptable. * Subject with the presence of acute infections in the areas intended for treatment. * Subject with known hypersensitivity to bovine collagen or to the components of the Apligraf agarose shipping medium. * Subject who is lactating or pregnant (positive result as determined by urine testing). * Subject with liver (ALT/SGPT, ALP, AST/SGOT, bilirubin, albumin, total protein, LDH) and/or renal function (BUN and creatinine) tests \> 2 x upper limit of normal (ULN). * Subject who has been previously enrolled in any wound or investigational device study for any disease within the past four weeks. * Subject who has received an investigational drug or biological treatment within the past three months. * Subject previously treated with Apligraf, Dermagraft or any other cell therapy at the target keloid site. * Subject with a history of alcohol or substance abuse within the previous year, which could interfere with study compliance such as inability to attend scheduled study visits or compliance with home dressing changes. * Subject with a history of anaphylaxis. * Subject who, in the opinion of the Investigator, for any reason other than those listed above, will not be able to complete the study per protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | 52 weeks | Summary of all reported adverse events (AE) in the intent to treat (ITT) population. AE was defined as any adverse change in the subject's medical status compared with the subject's baseline condition, whether or not the event was related to the study device or a study procedure; or an exacerbation (either in frequency or severity) in a subject's pre-existing condition. AE data were collected at every study visit or if volunteered by the subject at any time during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Degree of Keloid Recurrence as Measured by Beausang Scar Scale (BSS) | Baseline to Week 52 or Last Visit | Change in BSS cumulative score, Baseline to Last Visit, as reported by the Investigator, is reported. BSS is a composite score where the individual scores from the following categories are summed: Color (rated 1\[perfect\]-4\[gross mismatch\]), Shine (1/Matte or 2/Shiny), Contour (rated 1\[flush with surrounding skin\]-4\[keloid\]), Distortion (rated 1\[None\]-4\[severe\]), Texture (rated 1\[normal\]-4\[hard\]), and Overall Assessment on a 10cm visual analog scale (rated 0\[excellent scar\]-10 \[poor scar\]). Total score ranges from 5 (clinically well healed scar) - 28 (clinically poor scar). |
| Degree of Recurrence (Scar Firmness) | Week 52 or Last Visit | Scar firmness measured by Cutometer in millimeters. |
| Degree of Recurrence (Scar Thickness) | Week 52 or Last visit | Scar thickness measured by slide caliper in millimeters. A value of 0.0 mm on the slide caliper is equivalent to normal, non-hypertrophic/raised skin. |
| Cumulative Incidence of Keloid Recurrence at Week 52 | 52 weeks | Recurrence is defined the first study visit at which the Investigator scores the Contour component of the BSS with a 4 (indicating a keloid). Contour is one of the five components measured in the BSS with Contour scores ranging from 1 (flush with surrounding skin) to 4 (keloid). Recurrence is a negative outcome. |
| Subject Global Assessment | Week 52 or Last Visit | Subject assessed using 5 point scale (1-excellent, 2-very good, 3-good, 4-moderate, 5-poor) |
| Decreased Utilization of Intralesional Steroid Intervention | 52 weeks | The mean number of Intralesional (IL) Injections per participant is reported. A lower number of injections is a better outcome. |
| Physician Global Assessment | Week 52 or Last Visit | Investigator assessed using 5 point scale (1-excellent, 2-very good, 3-good, 4-moderate, 5-poor) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Apligraf Apligraf (bilayered living cellular construct) plus a dressing regimen comprised of a primary nonadherent dressing, dry gauze dressing and bolster gauze dressing, if necessary | 17 |
| Control Dressing regimen comprised of a primary nonadherent dressing, dry gauze dressing and bolster gauze dressing, if necessary | 13 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 1 |
Baseline characteristics
| Characteristic | Apligraf | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 13 Participants | 30 Participants |
| Age Continuous | 32.7 years STANDARD_DEVIATION 12.9 | 36.7 years STANDARD_DEVIATION 13.5 | 34.4 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 12 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 12 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 17 | 10 / 13 |
| serious Total, serious adverse events | 0 / 17 | 0 / 13 |
Outcome results
Primary
The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented.
Summary of all reported adverse events (AE) in the intent to treat (ITT) population. AE was defined as any adverse change in the subject's medical status compared with the subject's baseline condition, whether or not the event was related to the study device or a study procedure; or an exacerbation (either in frequency or severity) in a subject's pre-existing condition. AE data were collected at every study visit or if volunteered by the subject at any time during the study.
Time frame: 52 weeks
Population: ITT analysis per protocol. Report of at least 1 treatment emergent AE.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A (Apligraf) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Any AE | 12 Participants |
| A (Apligraf) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Unanticipated Adverse Device Effect (UADE) | 0 Participants |
| A (Apligraf) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Deaths | 0 Participants |
| A (Apligraf) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Serious Adverse Event (SAE) | 0 Participants |
| B (Control) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Deaths | 0 Participants |
| B (Control) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Any AE | 10 Participants |
| B (Control) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Serious Adverse Event (SAE) | 0 Participants |
| B (Control) | The Primary Purpose of This Study Will be to Gain Preliminary Safety Experience With Apligraf in the Keloid Indication. The Number of Participants Experiencing AEs is Presented. | Unanticipated Adverse Device Effect (UADE) | 0 Participants |
Comparison: Fisher's exact test used to evaluate treatment differences between Apligraf subjects and Control subjects experiencing any AEs.p-value: 1Fisher Exact
Secondary
Change in Degree of Keloid Recurrence as Measured by Beausang Scar Scale (BSS)
Change in BSS cumulative score, Baseline to Last Visit, as reported by the Investigator, is reported. BSS is a composite score where the individual scores from the following categories are summed: Color (rated 1\[perfect\]-4\[gross mismatch\]), Shine (1/Matte or 2/Shiny), Contour (rated 1\[flush with surrounding skin\]-4\[keloid\]), Distortion (rated 1\[None\]-4\[severe\]), Texture (rated 1\[normal\]-4\[hard\]), and Overall Assessment on a 10cm visual analog scale (rated 0\[excellent scar\]-10 \[poor scar\]). Total score ranges from 5 (clinically well healed scar) - 28 (clinically poor scar).
Time frame: Baseline to Week 52 or Last Visit
Population: Modified ITT (mITT) for randomized subjects only. Last Visit is the score recorded at last subject visit with non-missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Apligraf) | Change in Degree of Keloid Recurrence as Measured by Beausang Scar Scale (BSS) | -8.8 Units on a scale | Standard Deviation 5.1 |
| B (Control) | Change in Degree of Keloid Recurrence as Measured by Beausang Scar Scale (BSS) | -9.7 Units on a scale | Standard Deviation 4.3 |
p-value: 0.5863Wilcoxon (Mann-Whitney)
Secondary
Cumulative Incidence of Keloid Recurrence at Week 52
Recurrence is defined the first study visit at which the Investigator scores the Contour component of the BSS with a 4 (indicating a keloid). Contour is one of the five components measured in the BSS with Contour scores ranging from 1 (flush with surrounding skin) to 4 (keloid). Recurrence is a negative outcome.
Time frame: 52 weeks
Population: Cumulative assessment, mITT population for randomized subjects only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A (Apligraf) | Cumulative Incidence of Keloid Recurrence at Week 52 | 4 participants |
| B (Control) | Cumulative Incidence of Keloid Recurrence at Week 52 | 2 participants |
p-value: 0.3783Fisher Exact
Secondary
Decreased Utilization of Intralesional Steroid Intervention
The mean number of Intralesional (IL) Injections per participant is reported. A lower number of injections is a better outcome.
Time frame: 52 weeks
Population: mITT population (randomized subjects only)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Apligraf) | Decreased Utilization of Intralesional Steroid Intervention | 4.0 Injections per Participant | Standard Deviation 1.8 |
| B (Control) | Decreased Utilization of Intralesional Steroid Intervention | 4.2 Injections per Participant | Standard Deviation 1 |
Comparison: Differences evaluated using a 2-tailed Wilcoxon rank sum test with pooled variances.p-value: 0.9556Wilcoxon (Mann-Whitney)
Secondary
Degree of Recurrence (Scar Firmness)
Scar firmness measured by Cutometer in millimeters.
Time frame: Week 52 or Last Visit
Population: mITT population (randomized subjects only). Last Visit is the score recorded at last subject visit with non-missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Apligraf) | Degree of Recurrence (Scar Firmness) | 0.2 mm | Standard Deviation 0.1 |
| B (Control) | Degree of Recurrence (Scar Firmness) | 0.2 mm | Standard Deviation 0.1 |
Comparison: Treatment differences in scar firmness evaluated using a 2-tailed Wilcoxon rank sum test with pooled variances.p-value: 0.7149Wilcoxon (Mann-Whitney)
Secondary
Degree of Recurrence (Scar Thickness)
Scar thickness measured by slide caliper in millimeters. A value of 0.0 mm on the slide caliper is equivalent to normal, non-hypertrophic/raised skin.
Time frame: Week 52 or Last visit
Population: mITT population (randomized subjects only). Last Visit is the score recorded at last subject visit with non-missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Apligraf) | Degree of Recurrence (Scar Thickness) | 2.0 mm | Standard Deviation 2.2 |
| B (Control) | Degree of Recurrence (Scar Thickness) | 1.0 mm | Standard Deviation 1.1 |
Comparison: Treatment differences in scar thickness evaluated using a 2-tailed Wilcoxon rank sum testp-value: 0.167Wilcoxon (Mann-Whitney)
Secondary
Physician Global Assessment
Investigator assessed using 5 point scale (1-excellent, 2-very good, 3-good, 4-moderate, 5-poor)
Time frame: Week 52 or Last Visit
Population: mITT population (randomized subjects only). Last Visit is the score recorded at last subject visit with non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A (Apligraf) | Physician Global Assessment | Moderate | 5 Participants |
| A (Apligraf) | Physician Global Assessment | Very Good | 3 Participants |
| A (Apligraf) | Physician Global Assessment | Good | 0 Participants |
| A (Apligraf) | Physician Global Assessment | Poor | 1 Participants |
| A (Apligraf) | Physician Global Assessment | Excellent | 3 Participants |
| B (Control) | Physician Global Assessment | Excellent | 3 Participants |
| B (Control) | Physician Global Assessment | Poor | 1 Participants |
| B (Control) | Physician Global Assessment | Very Good | 3 Participants |
| B (Control) | Physician Global Assessment | Moderate | 4 Participants |
| B (Control) | Physician Global Assessment | Good | 2 Participants |
Comparison: Global assessments analyzed as ordinal ranks. Treatment differences in global assessment evaluated using a 2-tailed Wilcoxon rank sum test with pooled variances.p-value: 0.7221Wilcoxon (Mann-Whitney)
Secondary
Subject Global Assessment
Subject assessed using 5 point scale (1-excellent, 2-very good, 3-good, 4-moderate, 5-poor)
Time frame: Week 52 or Last Visit
Population: mITT population (randomized subjects only). Last Visit is the score recorded at last subject visit with non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A (Apligraf) | Subject Global Assessment | Very Good | 1 Participants |
| A (Apligraf) | Subject Global Assessment | Moderate | 2 Participants |
| A (Apligraf) | Subject Global Assessment | Good | 5 Participants |
| A (Apligraf) | Subject Global Assessment | Poor | 0 Participants |
| A (Apligraf) | Subject Global Assessment | Excellent | 4 Participants |
| B (Control) | Subject Global Assessment | Poor | 1 Participants |
| B (Control) | Subject Global Assessment | Excellent | 6 Participants |
| B (Control) | Subject Global Assessment | Very Good | 3 Participants |
| B (Control) | Subject Global Assessment | Good | 2 Participants |
| B (Control) | Subject Global Assessment | Moderate | 1 Participants |
Comparison: Global assessments analyzed as ordinal ranks. Treatment differences in global assessment evaluated using a 2-tailed Wilcoxon rank sum test with pooled variances.p-value: 0.408Wilcoxon (Mann-Whitney)