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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P030050 S002/ PAS002 |
| Date Original Protocol Accepted |
07/28/2009
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| Date Current Protocol Accepted |
05/01/2018
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| Study Name |
Clinical PAS
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| Device Name |
SCULPTRA AESTHETIC
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
No Control
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| Analysis Type |
Analytical
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| Study Population |
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
This is a 5-year prospective, open-label, multi-center study to be conducted in the United States in 35 clinical sites.
The overall objective is to assess the post market safety of SCULPTRA Aesthetic in immune-competent subjects when used as a single regimen for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles in persons with Fitzpatrick skin types I-VI.
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| Study Population |
Immuno-competent male or female subjects 18 to 75 years of age with NLF contour deficiencies and other facial wrinkles as defined by WAS criteria.
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| Sample Size |
With 604 evaluable subjects, the study has 80% power to ensure that the upper limit of the observed one-sided 95% confidence interval for the percentage of subjects with any injection site nodule and/or papule adverse event in 5 years will be less than 21% assuming that the actual percentage is p=17% (according to the 17% rate of nodule and/or papule from premarketing study DL6049-0301. The 21% upper bound rate is based upon agreements with FDA).
With 604 evaluable subjects, the study has 99% power to ensure that the upper limit of the observed one-sided 95% confidence interval for the percentage of subjects with any adverse event of interest other than nodule or papule in 5 years will be less than 3% assuming that the actual percentage is p=0.1% (according to the 0% rate of adverse event of interest other than nodule or papule from premarketing study DL6049-0301. The 3% upper bound rate is based upon agreements with FDA).
The study with 604 evaluable subjects will have an overall power close to 80% to achieve positive results for both the primary hypothesis tests because of 99% power for the second primary hypothesis test.
To ensure sufficient representation of dark skin subjects, the study will have at least 15 subjects with Fitzpatrick skin types IV and 85 subjects with Fitzpatrick skin types V-VI.
Assuming an annual dropout rate of 7% (30% in 5 years), the study will enroll approximately 863 subjects (at least 22 with Fitzpatrick skin type IV and 122 with Fitzpatrick skin type V-VI) in order to have a total of 604 evaluable subjects at the end of the study (at least 15 with Fitzpatrick skin type IV and 85 with Fitzpatrick skin type V-VI). When all subjects have completed two years of follow-up, the drop-out rate and other assumptions will be evaluated, and if necessary, additional subjects will be enrolled.
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| Key Study Endpoints |
The co-primary safety endpoints are:
¿ The percentage (incidence rate) of subjects with any injection site nodule and/or papule over 5 years.
¿ The percentage (incidence rate) of subjects with any of the following injection site events over 5 years:
¿ Hypertrophic scarring
¿ Keloid formation
¿ Changes in the skin pigmentation at the site of injection compared to adjacent skin
¿ Granuloma (confirmed by a biopsy)
¿ Skin necrosis
¿ Hypersensitivity reactions
¿ Unexpected change in wrinkle contour
The injection site adverse events listed above are defined as adverse events of interest in this study.
The secondary safety endpoints are:
¿ The percentages (incidence rate) of subjects with any injection site nodule and/or papule; the percentage of subjects who experienced any adverse events of interest other than injection site nodule or papule over 2 years; location and intervention for any adverse events of interest; adverse event severity, duration, time to onset, relationship to Sculptra® Aesthetic and relationship to injection procedure during the course of the study.
The secondary efficacy endpoints are:
¿ Change from baseline to post-treatment follow-up time points in the Global Assessments Scores (WAS) at Month 6, Month 13, and Years 2, 3, 4, and 5.
¿ Investigator/Subject GAS at Month 6, Month 13, and Years 2, 3, 4, and 5.
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| Follow-up Visits and Length of Follow-up |
5 years
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
867
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| Actual Number of Sites Enrolled |
20
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| Patient Follow-up Rate |
76.2% (661/867) at Year 5
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| Final Safety Findings |
In the intent-to-treat population (ITT, n = 867), the overall incidence rate of injection site nodules and/or papules (NPs) was 28.5% for subjects treated with Sculptra® Aesthetic in all treated facial areas (nasolabial folds, cheek folds, marionette lines, and chin crease). The incidence rates of NPs in each anatomic area were 19.0% (nasolabial folds), 5.4% (cheek folds), 27.2% (marionette lines), and 3.6% (chin crease). The overall incidence of adverse events of interest (AEIs) other than NPs was 1.0% of subjects treated with Sculptra® Aesthetic in all treated facial areas. Among subjects who completed Year 5 of the study (n = 661), the overall incidence rate of injection site NPs was 31.5% and the overall incidence rate of AEIs other than NPs was 0.9%. The overall incidence of NPs by treatment area were 21.0% (nasolabial folds), 6.3% (cheek folds), 29.1% (marionette lines), and 3.9% (chin crease). No trend of increasing NPs was observed with increasing number of Sculptra® Aesthetic injection sessions.
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| Final Effect Findings |
In all four anatomic locations, statistically significant changes from baseline (p<0.001) in average Wrinkle Assessment Scale (WAS) scores were observed at all timepoints through 5 years. However, the reductions (i.e., benefit) appeared to diminish over time. The overall mean change in the WAS score from baseline for nasolabial folds was -1.76, -1.73, -1.61, -1.19, -0.85, and -0.53 at the Month 6, Month 13, Year 2, Year 3, Year 4, and Year 5 visits, respectively. Investigators reported overall improvements from baseline using the Global Aesthetic Improvement Scale (GAIS) in 99.5%, 99.3%, 96.4%, 91.2%, 81.5%, and 68.8% of the subjects at the Month 6, Month 13, Year 2, Year 3, Year 4, and Year 5 visits, respectively. Subjects reported overall improvements from baseline using the GAIS of 97.4%, 97.4%, 91.7%, 86.5%, 74.4%, and 66.3% at the Month 6, Month 13, Year 2, Year 3, Year 4, and Year 5 visits, respectively.
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| Study Strengths & Weaknesses |
One study strength is that it was a prospective and multicenter investigation that provided long term data up to 5 years on the safety and effectiveness of the device. Weaknesses of the study include a high lost-to-follow-up rate (23.8%) and considerable site-to-site variability (0 – 79.1%). In addition, direct comparison of the incidence of NPs between the post-approval study and the original pivotal study is difficult due to differences in the collection and reporting of adverse events and because the original pivotal study
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| Recommendations for Labeling Changes |
Yes
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