Infraorbital Hollowing
Conditions
Brief summary
The objective of this study is to evaluate the safety and effectiveness of JUVÉDERM® VOLBELLA™ XC in adult participants seeking correction of hollowing of the tear troughs.
Interventions
DEVICEJUVÉDERM VOLBELLA® XC injectable gel
JUVÉDERM® VOLBELLA™ XC dermal filler injected into the infraorbital and adjacent area.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 22 or over and in good general health * Has Moderate or Severe infraorbital hollowing (grade 2 or 3 on the Allergan Infraorbital Hollows Scale (AIHS)) for each eye as assessed by the Evaluating Investigator (i.e., both eyes must qualify but do not need to have the same score) * Is able to complete effectiveness self-assessments without the use of glasses (contact lens use is acceptable if they will be used for all subject self-assessments) * Ability to follow study instructions and likely to complete all required visits * Written informed consent has been obtained
Exclusion criteria
* Has hyperpigmentation in the infraorbital area (does not include dark circles under the eyes not due to hyperpigmentation) * Has ever received permanent facial implants (e.g., polymethylmethacrylate, silicone, polytetrafluoroethylene) anywhere in the face or neck, or is planning to be implanted with any of these products during the study * Has ever undergone fat injections above the subnasale or is planning to undergo this procedure during the study * Has tattoos, piercings, facial hair (i.e., beard, mustache), or scars that would interfere with visual assessment of the infraorbital hollows * Has undergone volume augmentation with semipermanent dermal fillers (e.g., calcium hydroxyapatite, poly-L-lactic acid) or temporary dermal fillers in the malar area, temples, or around the eyes within 12 months before enrollment or is planning to undergo such treatment during the study * Has begun using any new over-the-counter or prescription oral or topical, anti-wrinkle products within 30 days before enrollment or is planning to begin using such products during the study. Subjects who have been on a regimen of such products for at least 30 days are eligible for the study if they intend to continue their regimen throughout the study) * Has active or recurrent inflammation or infection in either eye * Has active autoimmune disease * Females who are pregnant, nursing, or planning a pregnancy * Is an employee (or a relative of an employee) of the treating investigator (TI), evaluating investigator (EI), or Allergan, or a representative of Allergan * Has a condition or is in a situation which in the TI's opinion may put the subject at significant risk, may confound the study results, or may interfere significantly with the participant's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least a 1-point Improvement Change From Baseline on the Allergan Infraorbital Hollows Scale (AIHS) Based on Evaluating Investigator's (EI) Assessment | Baseline (Screening) to Month 3 post last treatment (JUVÉDERM® VOLBELLA™ XC arm) or Month 3 post randomization (No-treatment Control arm) | The evaluating investigator assessed hollowing in both infraorbital areas using the 5-point photonumeric AIHS where: 0=none (no visible hollowing or volume loss medially or laterally), 1=minimal (presence of hollowing with some volume loss medial to the mid-pupillary line; smooth lateral lid-cheek transition), 2=moderate (defined hollowing extending laterally beyond the mid-pupillary line with moderate volume loss; smooth lateral lid-cheek transition with mild volume loss), 3=severe (defined hollowing extending laterally beyond the mid-pupillary line with moderate volume loss creating a defined groove along the lid-cheek junction), 4=extreme (defined hollowing extends from medial to lateral canthus; severe volume loss creates a marked step along the lid-cheek junction). The percentage of participants with at least a 1-point improvement change (decrease) in the AIHS is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Improved or Much Improved in the Overall Aesthetic Assessment Based on EI's Assessment of the Global Aesthetic Improvement Scale (GAIS) at Month 3 After the Last Treatment | Baseline (Randomization) to Month 3 post last treatment (JUVÉDERM® VOLBELLA™ XC) or Month 3 post randomization (No-treatment Control arm) | The evaluating investigator assessed a participant's global aesthetic improvement in the infraorbital area compared to Baseline using the 5-point GAIS where: 2=much improved (marked improvement in appearance), 1=improved (improvement in appearance, but a touch-up or retreatment is indicated), 0=no change (appearance is essentially the same as the original condition), -1=worse (appearance is worse than the original condition), -2=much worse (appearance is much worse than the original condition). The percentage of participants where the EI selected improved or much improved is reported. |
| Percentage of Participants Improved or Much Improved in the Overall Aesthetic Assessment Based on Participant's Assessment of the GAIS at Month 3 After the Last Treatment | Baseline (Randomization) to Month 3 post last treatment | The participant assessed their global aesthetic improvement in the infraorbital area compared to Baseline using the 5-point GAIS where: 2=much improved (marked improvement in appearance), 1=improved (improvement in appearance, but a touch-up or retreatment is indicated), 0=no change (appearance is essentially the same as the original condition), -1=worse (appearance is worse than the original condition), -2=much worse (appearance is much worse than the original condition). The percentage of participants who selected improved or much improved is reported. |
| Mean Change From Baseline in Rasch-Transformed Score Based on Participant Responses on the FACE-Q™ Appraisal of Lower Eyelids Questionnaire to Month 3 After the Last Treatment | Baseline (Randomization) to Month 3 post last treatment | Participants assessed their overall satisfaction by using 7 questions on the validated Appraisal of Lower Eyelids module of the FACE-Q™ questionnaire. Each question was answered on a 4-point scale where: 1=not at all, 2=a little, 3=moderately, and 4=extremely bothered. The responses to the items were transformed to create a Rasch transformed score that ranges from 0=worst to 100=best. Higher scores indicate higher satisfaction. A positive change from Baseline indicates improvement. |
Countries
United States
Participant flow
Pre-assignment details
A total of 163 participants were enrolled in the study (signed the informed consent) out of which 140 were randomized to receive JUVÉDERM® VOLBELLA™ XC (treatment group) or no treatment (control group) in 3:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| No-treatment Control Participants randomized to the No-treatment Control group completed a 3-month No-treatment Period (Control Period). Participants were then eligible to receive optional treatment with JUVÉDERM® VOLBELLA™ XC injectable gel injected into the infraorbital and adjacent area followed by an optional touch-up treatment 1 month later. | 32 |
| JUVÉDERM® VOLBELLA™ XC JUVÉDERM® VOLBELLA™ XC injectable gel was injected into the infraorbital and adjacent area at Randomization as determined by the investigator. Participants were eligible to receive an optional touch-up treatment 1 month later and an optional repeat treatment 12 months after last treatment, if applicable. A maximum of 2.2 mL per side was injected for initial and touch-up treatments combined. | 103 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Missing Completion Status | 0 | 1 |
| Overall Study | Reason Not Specified | 0 | 1 |
| Overall Study | Withdrawal by Participant | 2 | 4 |
Baseline characteristics
| Characteristic | JUVÉDERM® VOLBELLA™ XC | Total | No-treatment Control |
|---|---|---|---|
| Age, Continuous | 44.9 years STANDARD_DEVIATION 10.58 | 43.9 years STANDARD_DEVIATION 10.73 | 41.0 years STANDARD_DEVIATION 10.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 18 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants | 117 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 18 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 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 | 81 Participants | 108 Participants | 27 Participants |
| Sex: Female, Male Female | 93 Participants | 124 Participants | 31 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 105 | 0 / 29 | 0 / 37 |
| other Total, other adverse events | 0 / 34 | 0 / 105 | 3 / 29 | 0 / 37 |
| serious Total, serious adverse events | 0 / 34 | 1 / 105 | 0 / 29 | 1 / 37 |
Outcome results
Primary
Percentage of Participants With at Least a 1-point Improvement Change From Baseline on the Allergan Infraorbital Hollows Scale (AIHS) Based on Evaluating Investigator's (EI) Assessment
The evaluating investigator assessed hollowing in both infraorbital areas using the 5-point photonumeric AIHS where: 0=none (no visible hollowing or volume loss medially or laterally), 1=minimal (presence of hollowing with some volume loss medial to the mid-pupillary line; smooth lateral lid-cheek transition), 2=moderate (defined hollowing extending laterally beyond the mid-pupillary line with moderate volume loss; smooth lateral lid-cheek transition with mild volume loss), 3=severe (defined hollowing extending laterally beyond the mid-pupillary line with moderate volume loss creating a defined groove along the lid-cheek junction), 4=extreme (defined hollowing extends from medial to lateral canthus; severe volume loss creates a marked step along the lid-cheek junction). The percentage of participants with at least a 1-point improvement change (decrease) in the AIHS is reported.
Time frame: Baseline (Screening) to Month 3 post last treatment (JUVÉDERM® VOLBELLA™ XC arm) or Month 3 post randomization (No-treatment Control arm)
Population: Modified Intent-to-treat (mITT) Population included participants who were randomized to study treatment (JUVÉDERM® VOLBELLA™ XC treatment group), received at least 1 study device treatment and had a Baseline and at least 1 posttreatment assessment of the primary effectiveness variable and participants who were randomized to the control group and had a Baseline and at least 1 follow-up assessment of the primary effectiveness variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| No-treatment Control | Percentage of Participants With at Least a 1-point Improvement Change From Baseline on the Allergan Infraorbital Hollows Scale (AIHS) Based on Evaluating Investigator's (EI) Assessment | 15.6 percentage of participants |
| JUVÉDERM® VOLBELLA™ XC | Percentage of Participants With at Least a 1-point Improvement Change From Baseline on the Allergan Infraorbital Hollows Scale (AIHS) Based on Evaluating Investigator's (EI) Assessment | 83.1 percentage of participants |
p-value: <0.000195% CI: [52.9, 82]Fisher Exact
Secondary
Mean Change From Baseline in Rasch-Transformed Score Based on Participant Responses on the FACE-Q™ Appraisal of Lower Eyelids Questionnaire to Month 3 After the Last Treatment
Participants assessed their overall satisfaction by using 7 questions on the validated Appraisal of Lower Eyelids module of the FACE-Q™ questionnaire. Each question was answered on a 4-point scale where: 1=not at all, 2=a little, 3=moderately, and 4=extremely bothered. The responses to the items were transformed to create a Rasch transformed score that ranges from 0=worst to 100=best. Higher scores indicate higher satisfaction. A positive change from Baseline indicates improvement.
Time frame: Baseline (Randomization) to Month 3 post last treatment
Population: VIT Population included participants who were randomized and received VOLBELLA™ treatment at the beginning of the Control Period. Overall number analyzed are the participants with data available for analyses at Baseline. Number analyzed is the number of participants with data available for analyses at a given time point. The FACE-Q™ was only completed by participants in the JUVÉDERM® VOLBELLA™ XC arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No-treatment Control | Mean Change From Baseline in Rasch-Transformed Score Based on Participant Responses on the FACE-Q™ Appraisal of Lower Eyelids Questionnaire to Month 3 After the Last Treatment | Baseline | 54.5 score on a scale | Standard Deviation 14.23 |
| No-treatment Control | Mean Change From Baseline in Rasch-Transformed Score Based on Participant Responses on the FACE-Q™ Appraisal of Lower Eyelids Questionnaire to Month 3 After the Last Treatment | Change From Baseline at Month 3 | 17.8 score on a scale | Standard Deviation 19.8 |
p-value: <0.0001t-test, 2 sided
Secondary
Percentage of Participants Improved or Much Improved in the Overall Aesthetic Assessment Based on EI's Assessment of the Global Aesthetic Improvement Scale (GAIS) at Month 3 After the Last Treatment
The evaluating investigator assessed a participant's global aesthetic improvement in the infraorbital area compared to Baseline using the 5-point GAIS where: 2=much improved (marked improvement in appearance), 1=improved (improvement in appearance, but a touch-up or retreatment is indicated), 0=no change (appearance is essentially the same as the original condition), -1=worse (appearance is worse than the original condition), -2=much worse (appearance is much worse than the original condition). The percentage of participants where the EI selected improved or much improved is reported.
Time frame: Baseline (Randomization) to Month 3 post last treatment (JUVÉDERM® VOLBELLA™ XC) or Month 3 post randomization (No-treatment Control arm)
Population: mITT Population included participants who were randomized to study treatment (JUVÉDERM® VOLBELLA™ XC treatment group), received at least 1 study device treatment and had a Baseline and at least 1 posttreatment assessment of the primary effectiveness variable and participants who were randomized to the control group and had a Baseline and at least 1 follow-up assessment of the primary effectiveness variable. Overall number analyzed are the participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| No-treatment Control | Percentage of Participants Improved or Much Improved in the Overall Aesthetic Assessment Based on EI's Assessment of the Global Aesthetic Improvement Scale (GAIS) at Month 3 After the Last Treatment | 12.5 percentage of participants |
| JUVÉDERM® VOLBELLA™ XC | Percentage of Participants Improved or Much Improved in the Overall Aesthetic Assessment Based on EI's Assessment of the Global Aesthetic Improvement Scale (GAIS) at Month 3 After the Last Treatment | 86.0 percentage of participants |
95% CI: [60.2, 86.8]
Secondary
Percentage of Participants Improved or Much Improved in the Overall Aesthetic Assessment Based on Participant's Assessment of the GAIS at Month 3 After the Last Treatment
The participant assessed their global aesthetic improvement in the infraorbital area compared to Baseline using the 5-point GAIS where: 2=much improved (marked improvement in appearance), 1=improved (improvement in appearance, but a touch-up or retreatment is indicated), 0=no change (appearance is essentially the same as the original condition), -1=worse (appearance is worse than the original condition), -2=much worse (appearance is much worse than the original condition). The percentage of participants who selected improved or much improved is reported.
Time frame: Baseline (Randomization) to Month 3 post last treatment
Population: VOLBELLA™ Initially Treated (VIT) Population included participants who were randomized and received VOLBELLA™ treatment at the beginning of the Control Period. Overall number analyzed are the participants with data available for analyses. The GAIS assessed by the participant was only completed by participants in the JUVÉDERM® VOLBELLA™ XC arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| No-treatment Control | Percentage of Participants Improved or Much Improved in the Overall Aesthetic Assessment Based on Participant's Assessment of the GAIS at Month 3 After the Last Treatment | 84.0 percentage of participants |