Improvement in Skin Laxity of the Lower Face and Submentum
Conditions
Brief summary
1. Demonstrate superiority of treatment with the Ulthera DeepSEE System compared to untreated control for the improvement of skin laxity of the lower face and submental area. 2. Demonstrate the safety of treatment with the Ulthera DeepSEE System for the improvement of skin laxity of the lower face and submental area.
Detailed description
Subjects in the study received a single treatment with Ulthera DeepSEE system on the midface, lower face, submental (under the chin) and upper neck area using 3 DeepSEE (DS) transducers (DS 10-1.5, DS 7-3.0, DS 7-4.5) at either Day 1 or Day 90. Subjects treated at Day 1 were followed for 180 days after treatment and subjects treated at Day 90 were followed for 90 days after treatment.
Interventions
DEVICEUltherapy treatment
Focused ultrasound energy delivered below the surface of the skin
DEVICEUntreated-control / delayed-treatment
Untreated-control, followed by Ultherapy treatment (focused ultrasound energy delivered below the surface of the skin)
Sponsors
Ulthera, Inc
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
\- Mild to moderate lower face and/or submental laxity that is amenable to improvement with non-invasive intervention and is not severe enough for surgical intervention;
Exclusion criteria
* Scarring in area(s) to be treated; * Any active implants (e.g., pacemakers or defibrillators) in the area(s) to be treated; * Any metallic implants in area(s) to be treated; * Any open wounds or lesions in the area(s) to be treated; * Body mass index (BMI) less than 19 or greater than 30; or * Gain or loss of ≥ 2 BMI units within the previous 90 days or has the intention to gain or lose ≥ 2 BMI units during the course of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Improvement in Lower Face and Submental Skin Laxity at Day 90 | Day 90 | Lower face and submental skin laxity were determined by three blinded evaluators after comparing Day 90 photographs with baseline photographs. Improvement was concluded if at least two evaluators assessed the Day 90 photographs as improved compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Displacement of Skin in the Submentum at Day 90 | Day 90 | Displacement of skin (in millimeters \[mm\]) in the submentum was determined by three-dimensional (3D) quantitative photographic analysis by comparing Day 90 photographs with baseline photographs. X-axis (lateral), Y-axis (vertical), and Z-axis (anterior to posterior) direction components were provided for both sides of the face combined (that is, overall). |
| Percentage of Subjects With Any Improvement on the Investigator Global Aesthetic Improvement Scale (iGAIS) at Day 90 as Assessed by the Treating Investigator in the Treatment Group | Day 90 | iGAIS ratings (-3 to +3 scores; lower scores meant worse outcome) used baseline photographs for comparison. Improvement was defined as a rating of +1, +2, or +3 on the iGAIS. |
| Percentage of Subjects With Any Improvement on the Subject Global Aesthetic Improvement Scale (sGAIS) at Day 90 as Assessed by the Subjects in the Treatment Group | Day 90 | sGAIS ratings (-3 to +3 scores; lower scores meant worse outcome) used baseline photographs for comparison. Improvement was defined as a rating of +1, +2, or +3 on the sGAIS. |
| Change From Baseline in FACE-Q Satisfaction With Lower Face and Jawline Score (Rasch-transformed) at Day 90, as Assessed by Subjects in Treatment Group | Baseline up to Day 90 | The subject assessed satisfaction using the Face-Q Satisfaction with Lower Face and Jawline module (1 \[very dissatisfied\] to 4 \[very satisfied\] scores; Rasch transformed score 0-100; higher scores meant better outcome). |
| Number of Subjects With at Least One Treatment-related Treatment-emergent Adverse Events (TEAEs) | From first treatment (Day 1) up to end of the study (EOS) (Up to Day 180) | — |
Countries
China
Participant flow
Recruitment details
Subjects were recruited from 5 investigational sites in China.
Pre-assignment details
Of the 213 screened subjects,12 were exited as screen failures and 201 subjects were enrolled and randomized in this study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Ulthera DeepSEE System Subjects were randomized to receive a single treatment with Ulthera DeepSEE system at Day 1. | 97 |
| Untreated Control/Delayed-treatment With Ulthera DeepSEE System Subjects were randomized and were untreated until Day 90 and then received a single treatment with Ulthera DeepSEE system. | 96 |
| Total | 193 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Other | 7 | 8 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Treatment With Ulthera DeepSEE System | Untreated Control/Delayed-treatment With Ulthera DeepSEE System | Total |
|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 7.57 | 47.3 years STANDARD_DEVIATION 7.24 | 47.1 years STANDARD_DEVIATION 7.39 |
| Race/Ethnicity, Customized Asian | 97 Participants | 96 Participants | 193 Participants |
| Sex: Female, Male Female | 91 Participants | 94 Participants | 185 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 97 | 0 / 96 |
| other Total, other adverse events | 34 / 97 | 32 / 96 |
| serious Total, serious adverse events | 3 / 97 | 0 / 96 |
Outcome results
Primary
Percentage of Subjects With Improvement in Lower Face and Submental Skin Laxity at Day 90
Lower face and submental skin laxity were determined by three blinded evaluators after comparing Day 90 photographs with baseline photographs. Improvement was concluded if at least two evaluators assessed the Day 90 photographs as improved compared to baseline.
Time frame: Day 90
Population: The full analysis set (FAS) included all subjects randomized with baseline photographs of acceptable quality.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Ulthera DeepSEE System | Percentage of Subjects With Improvement in Lower Face and Submental Skin Laxity at Day 90 | 54.2 percentage of subjects |
| Untreated Control/Delayed-treatment With Ulthera DeepSEE System | Percentage of Subjects With Improvement in Lower Face and Submental Skin Laxity at Day 90 | 47.0 percentage of subjects |
95% CI: [0.753, 2.4365]
Secondary
Change From Baseline in FACE-Q Satisfaction With Lower Face and Jawline Score (Rasch-transformed) at Day 90, as Assessed by Subjects in Treatment Group
The subject assessed satisfaction using the Face-Q Satisfaction with Lower Face and Jawline module (1 \[very dissatisfied\] to 4 \[very satisfied\] scores; Rasch transformed score 0-100; higher scores meant better outcome).
Time frame: Baseline up to Day 90
Population: FAS. This endpoint was pre-specified for the treatment group only. Here overall number of subjects analyzed were subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Ulthera DeepSEE System | Change From Baseline in FACE-Q Satisfaction With Lower Face and Jawline Score (Rasch-transformed) at Day 90, as Assessed by Subjects in Treatment Group | 30.3 score on a scale | Standard Deviation 23.39 |
Secondary
Displacement of Skin in the Submentum at Day 90
Displacement of skin (in millimeters \[mm\]) in the submentum was determined by three-dimensional (3D) quantitative photographic analysis by comparing Day 90 photographs with baseline photographs. X-axis (lateral), Y-axis (vertical), and Z-axis (anterior to posterior) direction components were provided for both sides of the face combined (that is, overall).
Time frame: Day 90
Population: FAS. Here overall number of subjects analyzed were subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Ulthera DeepSEE System | Displacement of Skin in the Submentum at Day 90 | X-axis | -0.0229 millimeter (mm) | Standard Deviation 0.5671 |
| Treatment With Ulthera DeepSEE System | Displacement of Skin in the Submentum at Day 90 | Y-axis | -0.1693 millimeter (mm) | Standard Deviation 0.7151 |
| Treatment With Ulthera DeepSEE System | Displacement of Skin in the Submentum at Day 90 | Z-axis | -0.2279 millimeter (mm) | Standard Deviation 1.1749 |
| Untreated Control/Delayed-treatment With Ulthera DeepSEE System | Displacement of Skin in the Submentum at Day 90 | X-axis | 0.0571 millimeter (mm) | Standard Deviation 0.5125 |
| Untreated Control/Delayed-treatment With Ulthera DeepSEE System | Displacement of Skin in the Submentum at Day 90 | Y-axis | -0.1352 millimeter (mm) | Standard Deviation 0.6336 |
| Untreated Control/Delayed-treatment With Ulthera DeepSEE System | Displacement of Skin in the Submentum at Day 90 | Z-axis | -0.4086 millimeter (mm) | Standard Deviation 1.1509 |
Comparison: X-axis95% CI: [-0.2395, 0.0683]
Comparison: Y-axis95% CI: [-0.2268, 0.1608]
Comparison: Z-axis95% CI: [-0.1551, 0.5133]
Secondary
Number of Subjects With at Least One Treatment-related Treatment-emergent Adverse Events (TEAEs)
Time frame: From first treatment (Day 1) up to end of the study (EOS) (Up to Day 180)
Population: SES.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Ulthera DeepSEE System | Number of Subjects With at Least One Treatment-related Treatment-emergent Adverse Events (TEAEs) | 36 Participants |
| Untreated Control/Delayed-treatment With Ulthera DeepSEE System | Number of Subjects With at Least One Treatment-related Treatment-emergent Adverse Events (TEAEs) | 34 Participants |
Secondary
Percentage of Subjects With Any Improvement on the Investigator Global Aesthetic Improvement Scale (iGAIS) at Day 90 as Assessed by the Treating Investigator in the Treatment Group
iGAIS ratings (-3 to +3 scores; lower scores meant worse outcome) used baseline photographs for comparison. Improvement was defined as a rating of +1, +2, or +3 on the iGAIS.
Time frame: Day 90
Population: FAS. This endpoint was pre-specified for the treatment group only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Ulthera DeepSEE System | Percentage of Subjects With Any Improvement on the Investigator Global Aesthetic Improvement Scale (iGAIS) at Day 90 as Assessed by the Treating Investigator in the Treatment Group | 96.8 percentage of subjects |
Secondary
Percentage of Subjects With Any Improvement on the Subject Global Aesthetic Improvement Scale (sGAIS) at Day 90 as Assessed by the Subjects in the Treatment Group
sGAIS ratings (-3 to +3 scores; lower scores meant worse outcome) used baseline photographs for comparison. Improvement was defined as a rating of +1, +2, or +3 on the sGAIS.
Time frame: Day 90
Population: FAS. This endpoint was pre-specified for the treatment group only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Ulthera DeepSEE System | Percentage of Subjects With Any Improvement on the Subject Global Aesthetic Improvement Scale (sGAIS) at Day 90 as Assessed by the Subjects in the Treatment Group | 94.7 percentage of subjects |