Mid-facial Volume Deficit Related to Aging
Conditions
Brief summary
Multicenter, single-blind, randomized, no-treatment control study to demonstrate the safety and effectiveness of VOLUMA XC for deep injection for cheek augmentation to correct age-related volume deficit in the mid-face.
Interventions
DEVICEJuvéderm® VOLUMA XC
Treating Investigator determines the appropriate volume of VOLUMA XC to be injected up to a maximum total of 12 mL for initial and touch-up treatment. One repeat treatment with up to 12 mL may be performed at the Subject's option after study completion.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female, 35-65 years of age * Zygomaticomalar region, anteromedial cheek, submalar region, and/or overall mid-facial volume deficit assessed by the Treating Investigator as grade 3, 4, or 5 on the photometric Mid-Face Volume Deficit Scale (MFVDS) * Desire cheek augmentation to correct age-related volume deficit in the mid-face * Accept the obligation not to receive any other facial procedures or treatments affecting facial volume deficit at any time during the study
Exclusion criteria
* Received (or is planning to receive) anti-coagulation, anti-platelet, or thrombolytic medications (e.g., warfarin), anti-inflammatory drugs \[oral/injectable corticosteroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)\], or other substances known to increase coagulation time from 10 days pre- to 3 days post injection \[Study device injections may be delayed as necessary to accommodate this 10-day wash-out period.\] * Have undergone facial plastic surgery (with the exception of rhinoplasty more than 2 years prior to enrollment), tissue grafting, or tissue augmentation with silicone, fat, or other permanent, or semi-permanent dermal fillers or be planning to undergo any of these procedures at any time during the study * Have undergone temporary facial dermal filler injections with hyaluronic acid-based fillers within 12 months, porcine-based collagen fillers within 24 months, or neuromodulator injections, mesotherapy, or resurfacing within 6 months prior to entry in the study or be planning to undergo any of these procedures at any time during the study * Have begun use of any new over-the-counter or prescription, oral or topical, anti-wrinkle products in the treatment area within 90 days prior to enrollment or be planning to begin use of such products at any time during the study. * Have very thin skin in the mid-facial region, tendency to accumulate fluid in the lower eyelids, or large infraorbital fat pads * Have mid-face volume deficit due to congenital defect, trauma, abnormalities in adipose tissue related to immune-mediated diseases such as generalized lipodystrophy, partial lipodystrophy, inherited disease, or HIV-related disease * Have a history of anaphylaxis, multiple severe allergies, atopy, or allergy to lidocaine (or any amide-based anesthetic), hyaluronic acid products, or Streptococcal protein, or have plans to undergo desensitization therapy during the term of the study * Have noticeable acne scarring, an active inflammation, infection, cancerous or pre-cancerous lesion, or unhealed wound or have undergone radiation treatment in the area to be treated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate Based on Improvement in Score on Validated 6-point Mid-Face Volume Deficit Scale (MFVDS) | 6 months | The primary effectiveness variable was responder rate for the treatment group. The investigator evaluated the volume deficit of the patient's face using the MFVDS 6-point scale where: 0=none (best) to 5=severe (worst). To be considered a responder, the average of the blinded, independent Evaluating Investigators' assessments of the participant's overall score on MFVDS at 6 months had to be improved (reduced) by ≥ 1 grade compared with the average of the Evaluating Investigator pre-treatment assessments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Treatment Effect | 24 Months | Duration of treatment effect was determined by Kaplan-Meier (KM) product limit estimate of the percentage of participants in the treatment group that maintained at least a 1-point improvement in the overall mid-face volume deficit score on the Mid-Face Volume Deficit Scale (MFVDS) based on the average of the 2 blinded Evaluating Investigators' assessments (with 95% Greenwood's Confidence Interval). |
| Responder Rate Based on Improvement in Score on Global Aesthetic Improvement Scale (GAIS) | 6 months | The investigator evaluated the patient's overall mid-face volume using the GAIS 5-point scale where: 2=much improved to -2=much worse. To be considered a responder, the average of the blinded, independent Evaluating Investigators' assessments of the participant's overall score on GAIS at 6 months had to be improved (reduced) by ≥ 1 grade compared with the average of the Evaluating Investigator pre-treatment assessments. |
| Responder Rate Based on Improvement in Score on MFVDS by Facial Region | 6 months | The investigator evaluated the volume deficit of the patient's face using the MFVDS 6-point scale where: 0=none (best) to 5=severe (worst). To be considered a responder, the average of the blinded, independent Evaluating Investigators' assessments of the participant's respective mid-facial area score on MFVDS at 6 months had to be improved (reduced) by ≥ 1 grade compared with the average of the Evaluating Investigator pre-treatment assessments. The percentage of responders is categorized by facial region. |
Countries
Canada, United States
Participant flow
Recruitment details
345 participants were originally recruited for treatment at 15 sites.
Pre-assignment details
Prior to randomization, 16 patients were excluded as screen failures and the first two participants per site (30 total) were treated as run-in participants. Of the 299 randomized participants, 17 were discontinued prior to treatment, leaving a modified intent-to-treat population of 282 participants (235 in Treatment Arm and 47 in Control Arm).
Participants by arm
| Arm | Count |
|---|---|
| VOLUMA® XC Treatment Arm Participants treated with JUVÉDERM® VOLUMA® XC Injectable Gel, volume determined by the investigator (up to 12 mLs) at study start. Participants were eligible for re-treatment if applicable. | 235 |
| Control Arm_No Treatment Then VOLUMA® XC No treatment for 6 months, then participants were treated with JUVÉDERM® VOLUMA® XC Injectable Gel, volume determined by the investigator (up to 12 mLs). Participants were eligible for re-treatment if applicable. | 47 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Initial Treatment Period | Adverse Event | 2 | 0 |
| Initial Treatment Period | Consent withdrawn | 22 | 9 |
| Initial Treatment Period | Discontinuation by Investigator/Sponsor | 2 | 0 |
| Initial Treatment Period | Ineligibility | 1 | 0 |
| Initial Treatment Period | Lost to Follow-up | 21 | 3 |
| Initial Treatment Period | Other Miscellaneous Reasons | 13 | 0 |
| Initial Treatment Period | Treated in Error | 0 | 3 |
Baseline characteristics
| Characteristic | VOLUMA® XC Treatment Arm | Control Arm_No Treatment Then VOLUMA® XC | Total |
|---|---|---|---|
| Age, Continuous | 54.4 Years STANDARD_DEVIATION 7.18 | 54.7 Years STANDARD_DEVIATION 5.95 | 54.4 Years STANDARD_DEVIATION 6.98 |
| Region of Enrollment Canada | 27 participants | 6 participants | 33 participants |
| Region of Enrollment United States | 208 participants | 41 participants | 249 participants |
| Sex: Female, Male Female | 189 Participants | 37 Participants | 226 Participants |
| Sex: Female, Male Male | 46 Participants | 10 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 270 | 15 / 167 |
| serious Total, serious adverse events | 11 / 270 | 2 / 167 |
Outcome results
Primary
Responder Rate Based on Improvement in Score on Validated 6-point Mid-Face Volume Deficit Scale (MFVDS)
The primary effectiveness variable was responder rate for the treatment group. The investigator evaluated the volume deficit of the patient's face using the MFVDS 6-point scale where: 0=none (best) to 5=severe (worst). To be considered a responder, the average of the blinded, independent Evaluating Investigators' assessments of the participant's overall score on MFVDS at 6 months had to be improved (reduced) by ≥ 1 grade compared with the average of the Evaluating Investigator pre-treatment assessments.
Time frame: 6 months
Population: Participants from the Modified-intent-to-treat (MITT) population, all participants randomized to treatment who received treatment and all participants randomized to no treatment control arm, with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VOLUMA® XC Treatment Arm | Responder Rate Based on Improvement in Score on Validated 6-point Mid-Face Volume Deficit Scale (MFVDS) | 85.6 percentage of responders |
| Control Arm_No Treatment Then VOLUMA® XC | Responder Rate Based on Improvement in Score on Validated 6-point Mid-Face Volume Deficit Scale (MFVDS) | 38.9 percentage of responders |
Secondary
Duration of Treatment Effect
Duration of treatment effect was determined by Kaplan-Meier (KM) product limit estimate of the percentage of participants in the treatment group that maintained at least a 1-point improvement in the overall mid-face volume deficit score on the Mid-Face Volume Deficit Scale (MFVDS) based on the average of the 2 blinded Evaluating Investigators' assessments (with 95% Greenwood's Confidence Interval).
Time frame: 24 Months
Population: Participants from the Modified-intent-to-treat (MITT) population, all participants randomized to the treatment arm who received treatment and all participants randomized to no treatment control arm who received treatment, with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VOLUMA® XC Treatment Arm | Duration of Treatment Effect | 44.6 Percentage of participants |
| Control Arm_No Treatment Then VOLUMA® XC | Duration of Treatment Effect | 44.9 Percentage of participants |
Secondary
Responder Rate Based on Improvement in Score on Global Aesthetic Improvement Scale (GAIS)
The investigator evaluated the patient's overall mid-face volume using the GAIS 5-point scale where: 2=much improved to -2=much worse. To be considered a responder, the average of the blinded, independent Evaluating Investigators' assessments of the participant's overall score on GAIS at 6 months had to be improved (reduced) by ≥ 1 grade compared with the average of the Evaluating Investigator pre-treatment assessments.
Time frame: 6 months
Population: Only those participants from the Modified-intent-to-treat (MITT) population randomized to the Treatment Arm who received treatment with available data are included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VOLUMA® XC Treatment Arm | Responder Rate Based on Improvement in Score on Global Aesthetic Improvement Scale (GAIS) | 81.8 Percentage of responders |
Secondary
Responder Rate Based on Improvement in Score on MFVDS by Facial Region
The investigator evaluated the volume deficit of the patient's face using the MFVDS 6-point scale where: 0=none (best) to 5=severe (worst). To be considered a responder, the average of the blinded, independent Evaluating Investigators' assessments of the participant's respective mid-facial area score on MFVDS at 6 months had to be improved (reduced) by ≥ 1 grade compared with the average of the Evaluating Investigator pre-treatment assessments. The percentage of responders is categorized by facial region.
Time frame: 6 months
Population: Only those participants from the Modified-intent-to-treat (MITT) population randomized to the Treatment Arm who received treatment with available data are included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VOLUMA® XC Treatment Arm | Responder Rate Based on Improvement in Score on MFVDS by Facial Region | Zygomaticomalar Region | 75.6 percentage of responders |
| VOLUMA® XC Treatment Arm | Responder Rate Based on Improvement in Score on MFVDS by Facial Region | Anteromedial Cheek | 83.3 percentage of responders |
| VOLUMA® XC Treatment Arm | Responder Rate Based on Improvement in Score on MFVDS by Facial Region | Submalar Region | 77.0 percentage of responders |