Volume Loss in the Infraorbital Hollow Area
Conditions
Brief summary
* Confirm the effectiveness of Belotero Balance® (+) Lidocaine (BBL) injection for the correction of volume loss in the infraorbital hollow (IOH) area by demonstrating superiority to untreated control. * Confirm the safety of BBL injection for the correction of volume loss in the IOH area.
Interventions
DEVICEBelotero Balance (+) Lidocaine, needle
Injection of Belotero Balance (+) Lidocaine to the infraorbital hollows using needles
DEVICEBelotero Balance (+) Lidocaine, cannula
Injection of Belotero Balance (+) Lidocaine into the infraorbital hollows using cannulas
DEVICEUntreated-control / delayed-treatment, needle
Untreated-control, followed by delayed-treatment with Belotero Balance (+) Lidocaine (injection of Belotero Balance (+) Lidocaine to the infraorbital hollows using needles)
DEVICEUntreated-control / delayed-treatment, cannulas
Untreated-control, followed by delayed-treatment with Belotero Balance (+) Lidocaine (injection of Belotero Balance (+) Lidocaine to the infraorbital hollows using cannulas)
Sponsors
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Is a candidate for bilateral IOH treatment. * Has symmetrical right and left IOHs with the same MIHAS score of 2 or 3 (moderate or severe), as assessed live by the blinded evaluator.
Exclusion criteria
* Prior lower-eyelid surgery, including orbital or midface surgery, or a permanent implant or graft in the midfacial region that could interfere with effectiveness assessments. * Previous treatment with fat injections or permanent and/or semi-permanent dermal fillers in the midfacial region. * Previous lower-eyelid and/or malar-region treatments with any dermal fillers (e.g., collagen, hyaluronic acid (HA), calcium hydroxyapatite, poly L-lactic acid (PLLA)) within the past 24 months. * Any other medical condition with the potential to interfere with the study outcome assessments or compromise subject safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate Based on Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8 | Week 8 | Responder rate was defined as percentage of subjects with treatment response at Week 8 on MIHAS, as assessed live by a blinded evaluator. Responders were defined as subjects who achieved greater than or equal to (\>=) 1 grade improvement on both IOHs on the MIHAS. MIHAS (to assess infraorbital hollow) was a 5-point scale ranging as: Grade 0 (none to minimal), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (extreme). A higher score indicated extreme signs of hollowing. This analysis was done using multiple imputation method to impute missing MIHAS scores. Percentage of subjects with response at Week 8 and corresponding confidence intervals were average values obtained from the multiple imputation approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Week 8 | The GAIS is a 7-point scale ranging as +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the investigator. An improvement on the GAIS was classified as improved, much improved, or very much improved. |
| Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Week 8 | The GAIS is a 7-point scale ranging as +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the subject. An improvement on the GAIS was classified as improved, much improved, or very much improved. |
| Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes at Week 8 | Baseline, Week 8 | The FACE-Q is a set of standardized patient-reported outcome scales for subjects undergoing facial cosmetic procedures. Subjects answered 7 questions of the FACE-Q satisfaction with eyes using a 4- point scale where: 1(very dissatisfied), 2 (somewhat dissatisfied), 3 (somewhat satisfied), 4 (very satisfied). The sum FACE-Q scores were Rasch-transformed and ranged from 0 to 100. Higher scores reflected a better outcome (greater satisfaction). |
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Related to BBL | BBL Treatment (Needle and Cannula): Up to 80 weeks; Control/Delayed-treatment BBL (Needle and Cannula): Up to 56 weeks | TEAEs are defined as adverse events (AEs) with onset or worsening on or after date and time of first dose of study treatment. A TEAE was considered to be related if a causal relationship between BBL and the TEAE is at least reasonably possible. |
| Number of Subjects With Treatment-Emergent Serious Adverse Events (TESAEs) Related to BBL | BBL Treatment (Needle and Cannula): Up to 80 weeks; Control/Delayed-treatment BBL (Needle and Cannula): Up to 56 weeks | TESAEs included TEAEs that resulted in death, required either inpatient hospitalization or the prolongation of hospitalization, were life-threatening, resulted in a persistent or significant disability/incapacity or resulted in a congenital anomaly/birth defect. A TESAE was considered to be related if a causal relationship between BBL and the TESAE is at least reasonably possible. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Subjects were recruited from 9 investigational sites in the United States.
Pre-assignment details
Of the 187 screened subjects, 37 were exited as screen failures.150 subjects were enrolled and randomized in this study.
Participants by arm
| Arm | Count |
|---|---|
| BBL Treatment With Needle Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection. | 49 |
| BBL Treatment With Cannula Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection. | 48 |
| Control/Delayed-treatment BBL With Needle Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection. | 27 |
| Control/Delayed-treatment BBL With Cannula Subjects were untreated until Week 8 and then received a single treatment of BBL injection using cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection. | 26 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 5 | 4 | 6 |
| Overall Study | Subject relocated | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 2 | 4 |
Baseline characteristics
| Characteristic | BBL Treatment With Needle | BBL Treatment With Cannula | Control/Delayed-treatment BBL With Needle | Control/Delayed-treatment BBL With Cannula | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 9.06 | 44.3 years STANDARD_DEVIATION 9.05 | 43.2 years STANDARD_DEVIATION 10.83 | 40.0 years STANDARD_DEVIATION 9.18 | 43.3 years STANDARD_DEVIATION 9.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 16 Participants | 7 Participants | 7 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 32 Participants | 20 Participants | 19 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants | 5 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 5 Participants | 2 Participants | 4 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 33 Participants | 19 Participants | 17 Participants | 109 Participants |
| Sex: Female, Male Female | 44 Participants | 36 Participants | 22 Participants | 23 Participants | 125 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 5 Participants | 3 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 48 | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 21 |
| other Total, other adverse events | 6 / 49 | 11 / 48 | 0 / 27 | 4 / 26 | 0 / 26 | 1 / 21 |
| serious Total, serious adverse events | 1 / 49 | 0 / 48 | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 21 |
Outcome results
Primary
Responder Rate Based on Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8
Responder rate was defined as percentage of subjects with treatment response at Week 8 on MIHAS, as assessed live by a blinded evaluator. Responders were defined as subjects who achieved greater than or equal to (\>=) 1 grade improvement on both IOHs on the MIHAS. MIHAS (to assess infraorbital hollow) was a 5-point scale ranging as: Grade 0 (none to minimal), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (extreme). A higher score indicated extreme signs of hollowing. This analysis was done using multiple imputation method to impute missing MIHAS scores. Percentage of subjects with response at Week 8 and corresponding confidence intervals were average values obtained from the multiple imputation approach.
Time frame: Week 8
Population: ITT. As planned, the data for this outcome measure was analyzed for pooled BBL treatment groups (needle and cannula), BBL treatment with needle group, BBL treatment with cannula group and pooled control/delayed-treatment groups BBL (needle and cannula).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BBL Treatment: All Subjects | Responder Rate Based on Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8 | 80.6 percentage of subjects |
| BBL Treatment With Needle | Responder Rate Based on Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8 | 87.4 percentage of subjects |
| BBL Treatment With Cannula | Responder Rate Based on Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8 | 73.7 percentage of subjects |
| Control/Delayed-treatment BBL: All Subjects | Responder Rate Based on Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8 | 1.9 percentage of subjects |
95% CI: [66.3, 85.6]
95% CI: [70.5, 92.3]
95% CI: [55.2, 82.5]
Secondary
Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes at Week 8
The FACE-Q is a set of standardized patient-reported outcome scales for subjects undergoing facial cosmetic procedures. Subjects answered 7 questions of the FACE-Q satisfaction with eyes using a 4- point scale where: 1(very dissatisfied), 2 (somewhat dissatisfied), 3 (somewhat satisfied), 4 (very satisfied). The sum FACE-Q scores were Rasch-transformed and ranged from 0 to 100. Higher scores reflected a better outcome (greater satisfaction).
Time frame: Baseline, Week 8
Population: ITT. Here overall number of subjects analyzed were subjects who were evaluable for this outcome measure that is, subjects with observed data. As planned, the data for this outcome measure was calculated and analyzed only for subjects randomized to the treatment groups (needle and cannula).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BBL Treatment: All Subjects | Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes at Week 8 | 27.4 score on a scale | Standard Deviation 26 |
| BBL Treatment With Needle | Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes at Week 8 | 24.6 score on a scale | Standard Deviation 27.9 |
Secondary
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Related to BBL
TEAEs are defined as adverse events (AEs) with onset or worsening on or after date and time of first dose of study treatment. A TEAE was considered to be related if a causal relationship between BBL and the TEAE is at least reasonably possible.
Time frame: BBL Treatment (Needle and Cannula): Up to 80 weeks; Control/Delayed-treatment BBL (Needle and Cannula): Up to 56 weeks
Population: The Safety Population (SP) included all treated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BBL Treatment: All Subjects | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Related to BBL | 5 Participants |
| BBL Treatment With Needle | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Related to BBL | 6 Participants |
| BBL Treatment With Cannula | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Related to BBL | 1 Participants |
| Control/Delayed-treatment BBL: All Subjects | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Related to BBL | 1 Participants |
Secondary
Number of Subjects With Treatment-Emergent Serious Adverse Events (TESAEs) Related to BBL
TESAEs included TEAEs that resulted in death, required either inpatient hospitalization or the prolongation of hospitalization, were life-threatening, resulted in a persistent or significant disability/incapacity or resulted in a congenital anomaly/birth defect. A TESAE was considered to be related if a causal relationship between BBL and the TESAE is at least reasonably possible.
Time frame: BBL Treatment (Needle and Cannula): Up to 80 weeks; Control/Delayed-treatment BBL (Needle and Cannula): Up to 56 weeks
Population: SP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BBL Treatment: All Subjects | Number of Subjects With Treatment-Emergent Serious Adverse Events (TESAEs) Related to BBL | 0 Participants |
| BBL Treatment With Needle | Number of Subjects With Treatment-Emergent Serious Adverse Events (TESAEs) Related to BBL | 0 Participants |
| BBL Treatment With Cannula | Number of Subjects With Treatment-Emergent Serious Adverse Events (TESAEs) Related to BBL | 0 Participants |
| Control/Delayed-treatment BBL: All Subjects | Number of Subjects With Treatment-Emergent Serious Adverse Events (TESAEs) Related to BBL | 0 Participants |
Secondary
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject
The GAIS is a 7-point scale ranging as +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the subject. An improvement on the GAIS was classified as improved, much improved, or very much improved.
Time frame: Week 8
Population: ITT. Here overall number of subjects analyzed were subjects who were evaluable for this outcome measure that is, subjects with observed data. As planned, the data for this outcome measure was calculated and analyzed only for subjects randomized to the treatment groups (needle and cannula).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BBL Treatment: All Subjects | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Improved (+1) | 19.6 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | No Change (0) | 0 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Worse (-1) | 0 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Much Worse (-2) | 0 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Very Much Worse (-3) | 0 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Very Much Improved (+3) | 34.8 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Much Improved (+2) | 45.7 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Improved (+1) | 32.6 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Very Much Worse (-3) | 0 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | No Change (0) | 0 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Much Improved (+2) | 37.2 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Worse (-1) | 0 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Very Much Improved (+3) | 30.2 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject | Much Worse (-2) | 0 percentage of subjects |
Secondary
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator
The GAIS is a 7-point scale ranging as +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the investigator. An improvement on the GAIS was classified as improved, much improved, or very much improved.
Time frame: Week 8
Population: ITT. Here overall number of subjects analyzed were subjects who were evaluable for this outcome measure that is, subjects with observed data. As planned, the data for this outcome measure was calculated and analyzed only for subjects randomized to the treatment groups (needle and cannula).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BBL Treatment: All Subjects | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Improved (+1) | 8.7 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Worse (-1) | 0 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Very Much Improved (+3) | 47.8 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Much Worse (-2) | 0 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | No Change (0) | 2.2 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Very Much Worse (-3) | 0 percentage of subjects |
| BBL Treatment: All Subjects | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Much Improved (+2) | 41.3 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Very Much Worse (-3) | 0 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Very Much Improved (+3) | 44.2 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Much Improved (+2) | 25.6 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Improved (+1) | 30.2 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | No Change (0) | 0 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Worse (-1) | 0 percentage of subjects |
| BBL Treatment With Needle | Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator | Much Worse (-2) | 0 percentage of subjects |