Infraorbital Hollows
Conditions
Keywords
Tear Trough
Brief summary
This is a prospective, randomized, evaluator-blinded, no-treatment controlled, parallel group, multi-center US study to evaluate the safety and effectiveness of Restylane-L® for correction of Infraorbital Hollows.
Interventions
DEVICERestylane-L®
Intradermal injection.
Sponsors
Galderma R&D
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
* Moderate or severe infraorbital hollows with no more than one grade difference between the left and right side at baseline as assessed by the blinded evaluator. * Males or non-pregnant, non-breastfeeding females, over the age of 21. * Intent to undergo correction of both orbital hollows.
Exclusion criteria
* Known/previous allergy or hypersensitivity to any injectable hyaluronic acid (HA) gel or to gram positive bacterial proteins. * Known/previous allergy or hypersensitivity to local anesthetics, e.g. lidocaine or other amide-type anesthetics. * Previous deep and/or superficial facial dermal therapies. * Active or a history of recurrent or chronic infraorbital edema or rosacea or uncontrolled severe seasonal allergies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate Based on the Blinded Evaluator's Live Assessment of the Galderma Infraorbital Hollows Scale (GIHS) | At 3 months after Baseline | Responder rate was defined as the percentage of participants with at least a 1-point improvement from baseline on the Galderma Infraorbital Hollows Scale (GIHS), on both sides of the face, concurrently. GIHS is a validated 4-point scale used to assess Infraorbital Hollows: 0 (none \[hollowness\]), 1 (mild \[hollowness\]), 2 (moderate \[hollowness\]), 3 (severe \[hollowness\]). Higher score means more severe (worse) hollowness in the infraorbital Hollows. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At 6, 9, and 12 months after Baseline and at 3 and 6 months after optional treatment | Responder rate was defined as the percentage of participants with at least a 1-point improvement from baseline on the GIHS, on both sides of the face, concurrently at each of the timepoints. GIHS is a validated 4-point scale used to assess Infraorbital Hollows: 0 (none \[hollowness\]), 1 (mild \[hollowness\]), 2 (moderate \[hollowness\]), 3 (severe \[hollowness\]). Higher score means more severe (worse) hollowness in the infraorbital Hollows. |
| Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At 1, 3, 6, 9, and 12 months after randomization, at 1 month after optional touch-up, and at 1, 3 and 6 months after optional treatment | GAIS responder rates are based on independent assessments by the participant. Responder rate was defined as the percentage of participants with at least Improved when compared to baseline before first treatment. The 7-graded GAIS was used by the participant to live assess the aesthetic improvement of the infraorbital hollows by responding to the question: How would you describe the aesthetic improvement of your tear troughs today compared to the photograph taken before treatment? by using the respective categorical scale as follows; Very Much Improved, Much Improved, Improved, No Change, Worse, Much Worse, Very Much Worse. |
| Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At 1, 3, 6, 9, and 12 months after randomization, at 1 month after optional touch-up, and at 1, 3 and 6 months after optional treatment | GAIS responder rates are based on independent assessments by the Treating Investigator. Responder rate was defined as the percentage of participants with at least Improved when compared to baseline before first treatment. The 7-graded GAIS was used by the treating investigator to live assess the aesthetic improvement of the infraorbital hollows by responding to the question: How would you describe the aesthetic improvement of participant's tear troughs today compared to the photograph taken before treatment? by using the respective categorical scale as follows; Very Much Improved, Much Improved, Improved, No Change, Worse, Much Worse, Very Much Worse. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 16 sites in the United States from 11 November 2019 to 06 April 2022.
Participants by arm
| Arm | Count |
|---|---|
| Restylane-L® Treatment Participants were injected with Restylane-L® intradermal injection using either needle or cannula on Day 1, optional touch-up injection administered at 1 month of initial treatment. | 287 |
| No Treatment Control No-treatment control group did not receive any treatment during the main study period. | 46 |
| Total | 333 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 14 | 6 |
| Overall Study | Other | 6 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 6 |
| Overall Study | Withdrew consent- Covid-19 related | 2 | 1 |
Baseline characteristics
| Characteristic | No Treatment Control | Restylane-L® Treatment | Total |
|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 12.27 | 44.3 years STANDARD_DEVIATION 11.58 | 44.4 years STANDARD_DEVIATION 11.67 |
| Blinded Evaluator GIHS score - left 0 | 0 Participants | 0 Participants | 0 Participants |
| Blinded Evaluator GIHS score - left 1 | 0 Participants | 0 Participants | 0 Participants |
| Blinded Evaluator GIHS score - left 2 | 27 Participants | 147 Participants | 174 Participants |
| Blinded Evaluator GIHS score - left 3 | 19 Participants | 140 Participants | 159 Participants |
| Blinded Evaluator GIHS score - right 0 | 0 Participants | 0 Participants | 0 Participants |
| Blinded Evaluator GIHS score - right 1 | 0 Participants | 0 Participants | 0 Participants |
| Blinded Evaluator GIHS score - right 2 | 24 Participants | 147 Participants | 171 Participants |
| Blinded Evaluator GIHS score - right 3 | 22 Participants | 140 Participants | 162 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 66 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 221 Participants | 258 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick skin type (FST) FST I | 0 Participants | 5 Participants | 5 Participants |
| Fitzpatrick skin type (FST) FST II | 11 Participants | 75 Participants | 86 Participants |
| Fitzpatrick skin type (FST) FST III | 20 Participants | 117 Participants | 137 Participants |
| Fitzpatrick skin type (FST) FST IV | 10 Participants | 62 Participants | 72 Participants |
| Fitzpatrick skin type (FST) FST V | 3 Participants | 13 Participants | 16 Participants |
| Fitzpatrick skin type (FST) FST VI | 2 Participants | 15 Participants | 17 Participants |
| Race/Ethnicity, Customized White Asian | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized White Black or African American | 4 Participants | 17 Participants | 21 Participants |
| Race/Ethnicity, Customized White Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White Other | 2 Participants | 8 Participants | 10 Participants |
| Race/Ethnicity, Customized White White | 39 Participants | 257 Participants | 296 Participants |
| Sex: Female, Male Female | 38 Participants | 252 Participants | 290 Participants |
| Sex: Female, Male Male | 8 Participants | 35 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 287 | 0 / 46 |
| other Total, other adverse events | 97 / 287 | 6 / 46 |
| serious Total, serious adverse events | 4 / 287 | 0 / 46 |
Outcome results
Primary
Responder Rate Based on the Blinded Evaluator's Live Assessment of the Galderma Infraorbital Hollows Scale (GIHS)
Responder rate was defined as the percentage of participants with at least a 1-point improvement from baseline on the Galderma Infraorbital Hollows Scale (GIHS), on both sides of the face, concurrently. GIHS is a validated 4-point scale used to assess Infraorbital Hollows: 0 (none \[hollowness\]), 1 (mild \[hollowness\]), 2 (moderate \[hollowness\]), 3 (severe \[hollowness\]). Higher score means more severe (worse) hollowness in the infraorbital Hollows.
Time frame: At 3 months after Baseline
Population: The modified intention-to-treat (mITT) population included all participants who were randomized and analyzed according to the randomization scheme and who did not have a GIHS Month 3 visit assessment conducted remotely (i.e., remote study visit and/or GIHS assessment performed remotely).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Restylane-L® Treatment | Responder Rate Based on the Blinded Evaluator's Live Assessment of the Galderma Infraorbital Hollows Scale (GIHS) | 87.4 Percentage of participants |
| No Treatment Control | Responder Rate Based on the Blinded Evaluator's Live Assessment of the Galderma Infraorbital Hollows Scale (GIHS) | 17.7 Percentage of participants |
p-value: <0.00195% CI: [52.54, 86.89]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment
GAIS responder rates are based on independent assessments by the Treating Investigator. Responder rate was defined as the percentage of participants with at least Improved when compared to baseline before first treatment. The 7-graded GAIS was used by the treating investigator to live assess the aesthetic improvement of the infraorbital hollows by responding to the question: How would you describe the aesthetic improvement of participant's tear troughs today compared to the photograph taken before treatment? by using the respective categorical scale as follows; Very Much Improved, Much Improved, Improved, No Change, Worse, Much Worse, Very Much Worse.
Time frame: At 1, 3, 6, 9, and 12 months after randomization, at 1 month after optional touch-up, and at 1, 3 and 6 months after optional treatment
Population: ITT population included all participants who were randomized and analyzed according to the randomization scheme. Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and number analyzed refer to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 3 | 97.7 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 6 | 95.3 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 9 | 92.5 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 12 | 87.5 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 1 after optional touch up | 99.5 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 1 after optional treatment | 100 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 3 after optional treatment | 97.4 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 6 after optional treatment | 99.4 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 1 | 97.4 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 3 | 5.1 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 1 | 2.9 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 6 | 10.8 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 1 after optional treatment | 100 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 9 | 5.6 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 6 after optional treatment | 89.7 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 12 | 2.8 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the GAIS Based on the Treating Investigator Live Assessment | At Month 3 after optional treatment | 96.6 Percentage of participants |
Secondary
Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment
GAIS responder rates are based on independent assessments by the participant. Responder rate was defined as the percentage of participants with at least Improved when compared to baseline before first treatment. The 7-graded GAIS was used by the participant to live assess the aesthetic improvement of the infraorbital hollows by responding to the question: How would you describe the aesthetic improvement of your tear troughs today compared to the photograph taken before treatment? by using the respective categorical scale as follows; Very Much Improved, Much Improved, Improved, No Change, Worse, Much Worse, Very Much Worse.
Time frame: At 1, 3, 6, 9, and 12 months after randomization, at 1 month after optional touch-up, and at 1, 3 and 6 months after optional treatment
Population: ITT population included all participants who were randomized and analyzed according to the randomization scheme. Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and number analyzed refer to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 1 | 93.0 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 1 after optional touch up | 99.0 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 1 after optional treatment | 98.7 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 3 | 95.0 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 3 after optional treatment | 94.3 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 9 | 88.1 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 6 after optional treatment | 93.0 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 6 | 91.8 Percentage of participants |
| Restylane-L® Treatment | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 12 | 79.8 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 6 after optional treatment | 82.8 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 3 | 2.6 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 6 | 0 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 9 | 0 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 12 | 2.8 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 1 after optional treatment | 93.8 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 3 after optional treatment | 89.7 Percentage of participants |
| No Treatment Control | Percentage of Participants With At Least Improved on the Global Aesthetic Improvement Scale (GAIS) Based on the Participants Live Assessment | At Month 1 | 2.9 Percentage of participants |
Secondary
Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment
Responder rate was defined as the percentage of participants with at least a 1-point improvement from baseline on the GIHS, on both sides of the face, concurrently at each of the timepoints. GIHS is a validated 4-point scale used to assess Infraorbital Hollows: 0 (none \[hollowness\]), 1 (mild \[hollowness\]), 2 (moderate \[hollowness\]), 3 (severe \[hollowness\]). Higher score means more severe (worse) hollowness in the infraorbital Hollows.
Time frame: At 6, 9, and 12 months after Baseline and at 3 and 6 months after optional treatment
Population: mITT population included all participants who were randomized and analyzed according to the randomization scheme and who did not have a GIHS Month 3 visit assessment conducted remotely (that is \[i.e.\], remote study visits and/or GIHS assessment performed remotely). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and number analyzed refer to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Restylane-L® Treatment | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 3 after optional treatment | 87.1 Percentage of participants |
| Restylane-L® Treatment | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 9 | 77.6 Percentage of participants |
| Restylane-L® Treatment | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 12 | 63.5 Percentage of participants |
| Restylane-L® Treatment | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 6 after optional treatment | 80.3 Percentage of participants |
| Restylane-L® Treatment | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 6 | 86.0 Percentage of participants |
| No Treatment Control | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 6 after optional treatment | 65.5 Percentage of participants |
| No Treatment Control | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 3 after optional treatment | 82.8 Percentage of participants |
| No Treatment Control | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 6 | 13.5 Percentage of participants |
| No Treatment Control | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 12 | 11.1 Percentage of participants |
| No Treatment Control | Responder Rate Based on the Blinded Evaluator's Live Assessment of the GIHS at 6, 9, and 12 Months After Baseline And at 3 and 6 Months After Optional Treatment | At Month 9 | 11.1 Percentage of participants |
Comparison: Responder Rate Based on the Blinded Evaluator's live assessment of the GIHS at 6 Months After Baselinep-value: <0.00195% CI: [60.67, 84.28]Cochran-Mantel-Haenszel
Comparison: Responder Rate Based on the Blinded Evaluator's live assessment of the GIHS at 9 Months After Baselinep-value: <0.00195% CI: [54.97, 77.92]Cochran-Mantel-Haenszel
Comparison: Responder Rate Based on the Blinded Evaluator's live assessment of the GIHS at 12 Months After Baselinep-value: <0.00195% CI: [40.57, 64.26]Cochran-Mantel-Haenszel