A Multicenter, Evaluator-blinded, Randomized, No-treatment Controlled Study to Evaluate the Safety and Effectiveness of JUVÉDERM® VOLUMA® With Lidocaine for Correction of Temple Hollowing in Chinese Population
Phase: PHASE3
Conditions: Temple Hollowing
Sponsor: Allergan



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Protocol 1878-701-008 Amd 3
JUVÉDERM® VOLUMA® with Lidocaine injectable gel
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Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Amendment 3
January 2022
Amendment 2
December 2020
Amendment 1
August 2020
Original Protocol
December 2019
Amendment 3 (January 2022)
Overall Rationale for the Amendment:
The primary purpose of this protocol amendment is to include acceptable protocol modifications 
due to travel restrictions or other pandemic or natural disaster-related reasons.
Section No. and Name
Description of Change
Brief Rationale
Cover page
Added contacts for emergency 
and non-emergency events, 
safety concerns, updated the 
SAE/SADE reporting fax and 
email, and added additional 
signatories 
To align with 
current SOPs and 
templates
Section 1.3/ Schedule of Activities: Table 1-2
and Table 1-3
Modified from 3D digital 
imaging to 3D facial imaging
To clarify it is 
facial imaging
Section 1.3/ Schedule of Activities: Table 1-2
Changed footnote for vital sign 
at randomization visit from f to 
g
To correct a 
typographical 
error
Section 1.1/ Synopsis,
Section 1.3/ Schedule of Activities,
Section 2.3/ Benefit/Risk Assessment,
Sections 4.1/ Overall Design,
Section 4.4/ End of Study Definition,
Section 5.1/ Inclusion Criteria, 
Section 7.2/ Participant Discontinuation 
Withdrawal from the Study, 
Section 8/ Study Assessment and Procedures, 
Section 8.1/ Efficacy Assessments, 
Section 8.2/ Safety Assessments,
Section 8.3/ Adverse Events and Serious 
Adverse Events,
Section 9.2/ Sample Size Determination,
Section 10.1.1/ Regulatory and Ethical 
Considerations,
Section 10.1.3/ Informed Consent Process,
Added language for protocol 
modifications due to pandemic 
and natural disaster
To align with the
'Guidelines for the 
management of 
drug clinical trials 
during COVID-
19', SOPs, and 
template to reduce 
the impact of the 
pandemic on the 
clinical trial and 
the follow-up of 
the subjects
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Section No. and Name
Description of Change
Brief Rationale
Section 10.1.6/ Data Quality Assurance, and
Section 10.1.10/ Compliance with the Protocol
Section 4.1/ Overall Design and Section 9.2/ 
Sample Size Determination  
Updated number of 
investigational sites and sample 
size calculations  
Added new site to 
support the 
enrollment
Section 5.2/ Exclusion Criteria,
Modified exclusion criteria
number 4.01 by adding “which 
will have impact to study 
treatment, evaluation, and 
outcome
To clarify only 
excluding 
participant who 
has abnormal and 
clinically 
significant results 
that will have 
impact to study 
treatment, 
evaluation, and 
outcome 
according to TI or 
designee
Section 6.1.2/ Instructions for Use and 
Administration  
Added related Chinese 
guidelines on treatment safety
To provide 
references for
treatment safety 
management
Section 8.1/ Effectiveness Assessments
Added language of assessments 
procedures
To maintain 
consistency of 
assessments 
between visits and 
evaluators
Section 8.2.1/ Clinical Safety Laboratory 
Assessments 
Removed reference to 
laboratory manual 
Update
Section 8.3.5/ Pregnancy 
Clarified that pregnancy 
outcomes can include elective 
or therapeutic abortions
To align with 
current SOPs and 
templates
Section 10.1.4/ Data Protection
Added language to clarify that 
facial images are included 
To align with 
current SOPs and 
templates
Section 11/ References 
Added reference 
Update
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Table of Contents
Title Page ........................................................................................................................................1
Protocol Amendment Summary of Changes Table ....................................................................3
Table of Contents...........................................................................................................................5
List of Tables ..................................................................................................................................7
1.
Protocol Summary ..........................................................................................................8
1.1.
Synopsis............................................................................................................................8
1.2.
Schema............................................................................................................................10
1.3.
Schedule of Activities.....................................................................................................11
2.
Introduction...................................................................................................................16
2.1.
Study Rationale...............................................................................................................16
2.2.
Background.....................................................................................................................16
2.3.
Benefit/Risk Assessment ................................................................................................18
3.
Objectives and Endpoints ............................................................................................20
4.
Study Design..................................................................................................................21
4.1.
Overall Design ................................................................................................................21
4.2.
Scientific Rationale for Study Design ............................................................................22
4.2.1.
Participant Input into Design ..........................................................................................22
4.2.2.
No-treatment Control......................................................................................................22
4.2.3.
Evaluator Blinded ...........................................................................................................22
4.2.4.
Allergan Temple Hollowing Scale..................................................................................23
4.2.5.
FACE-Q Questionnaire...................................................................................................23
4.3.
Justification for Dose......................................................................................................23
4.4.
End of Study Definition..................................................................................................24
5.
Study Population...........................................................................................................25
5.1.
Inclusion Criteria ............................................................................................................25
5.2.
Exclusion Criteria ...........................................................................................................25
5.3.
Lifestyle Considerations .................................................................................................27
5.4.
Screen Failures................................................................................................................27
6.
Study Intervention........................................................................................................28
6.1.
Study Intervention Administered....................................................................................28
6.1.1.
Medical Devices..............................................................................................................28
6.1.2.
Instructions for Use and Administration.........................................................................29
6.2.
Preparation/Handling/Storage/Accountability................................................................30
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................30
6.4.
Study Intervention Compliance ......................................................................................31
6.5.
Concomitant Therapy .....................................................................................................31
6.5.1.
Rescue Medicine.............................................................................................................32
6.5.2.
Prohibited Therapy and Washout Before the Study .......................................................32
6.5.3.
Permitted Interventions...................................................................................................33
6.5.4.
Prohibited Interventions During the Study .....................................................................33
6.6.
Dose Modification ..........................................................................................................34
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6.6.1.
Retreatment Criteria........................................................................................................34
6.7.
Intervention after the End of the Study...........................................................................34
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................35
7.1.
Discontinuation of Study Intervention............................................................................35
7.2.
Participant Discontinuation/Withdrawal from the Study................................................35
7.3.
Lost to Follow-up............................................................................................................36
8.
Study Assessments and Procedures.............................................................................38
8.1.
Effectiveness Assessments .............................................................................................39
8.1.1.
Intervention Administration Assessments ......................................................................39
8.1.2.
Primary Effectiveness Measure ......................................................................................39
8.1.3.
Secondary Effectiveness Measures.................................................................................40
8.1.4.
Other Effectiveness Measures.........................................................................................42
8.2.
Safety Assessments.........................................................................................................44
8.2.1.
Clinical Safety Laboratory Assessments ........................................................................45
8.3.
Adverse Events and Serious Adverse Events .................................................................46
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................46
8.3.2.
Method of Detecting AEs and SAEs ..............................................................................47
8.3.3.
Follow-up of AEs and SAEs...........................................................................................47
8.3.4.
Regulatory Reporting Requirements for SAEs...............................................................48
8.3.5.
Pregnancy........................................................................................................................48
8.3.6.
Medical Device Deficiencies..........................................................................................48
8.4.
Treatment of Overdose ...................................................................................................49
8.5.
Pharmacokinetics............................................................................................................50
8.6.
Pharmacodynamics .........................................................................................................50
8.7.
Genetics ..........................................................................................................................50
8.8.
Biomarkers......................................................................................................................50
8.9.
Immunogenicity Assessments.........................................................................................50
8.10.
Health Economics...........................................................................................................50
9.
Statistical Considerations.............................................................................................51
9.1.
Statistical Hypotheses.....................................................................................................51
9.2.
Sample Size Determination ............................................................................................51
9.3.
Populations for Analyses ................................................................................................53
9.4.
Statistical Analyses.........................................................................................................53
9.4.1.
General Considerations...................................................................................................53
9.4.2.
Primary Endpoint............................................................................................................54
9.4.3.
Secondary Endpoints ......................................................................................................55
9.4.4.
Additional Endpoints ......................................................................................................56
9.4.5.
Safety Analyses...............................................................................................................57
9.4.6.
Other Analyses................................................................................................................58
9.5.
Interim Analyses.............................................................................................................58
9.6.
Data Monitoring Committee...........................................................................................59
10.
Supporting Documentation and Operational Considerations..................................60
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10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................60
10.1.1.
Regulatory and Ethical Considerations...........................................................................60
10.1.2.
Financial Disclosure........................................................................................................61
10.1.3.
Informed Consent Process ..............................................................................................61
10.1.4.
Data Protection................................................................................................................61
10.1.5.
Dissemination of Clinical Study Data.............................................................................62
10.1.6.
Data Quality Assurance ..................................................................................................62
10.1.7.
Source Documents ..........................................................................................................63
10.1.8.
Study and Site Start and Closure ....................................................................................63
10.1.9.
Publication Policy...........................................................................................................64
10.1.10. Compliance with Protocol...............................................................................................64
10.2.
Appendix 2: Clinical Laboratory Tests...........................................................................65
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.........................................................66
10.4.
Appendix 4: Abbreviations.............................................................................................67
10.5.
Appendix 5: Standard Discontinuation Criteria..............................................................68
10.6.
Appendix 6: Study Tabular Summary ............................................................................69
10.7.
Appendix 7: AEs, ADEs, SAEs, SADEs, and Device 
Deficiencies: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting in Medical Device Studies ................................71
10.7.1.
Definition of AE and ADE .............................................................................................71
10.7.2.
Definition of SAE, SADE, and USADE.........................................................................72
10.7.3.
Definition of Device Deficiency.....................................................................................73
10.7.4.
Recording and Follow-up of AE and/or SAE and Device 
Deficiencies.....................................................................................................................73
10.7.5.
Reporting of SAEs ..........................................................................................................75
10.7.6.
Reporting of SADEs .......................................................................................................76
10.8.
Appendix 8: Protocol Amendment History ....................................................................77
11.
References......................................................................................................................79
List of Tables
Table 1-1
Screening Visit Procedures: All Participants .................................................... 11
Table 1-2
Treatment Group Procedures ............................................................................ 12
Table 1-3
Control Group Procedures................................................................................. 14
Table 6-1
Study Interventions ........................................................................................... 28
Table 6-2
Required Washout Intervals for Prohibited Therapy Prior to Baseline ............ 33
Table 8-1
Allergan Temple Hollowing Scale.................................................................... 40
Table 8-2
Global Aesthetic Improvement Scale................................................................ 40
Table 10-1
Protocol-Required Safety Laboratory Assessments.......................................... 65
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1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A multicenter, evaluator-blinded, randomized, no-treatment controlled study to 
evaluate the safety and effectiveness of JUVÉDERM® VOLUMA® with Lidocaine for correction 
of temple hollowing in Chinese population
Short Title: JUVÉDERM® VOLUMA® with Lidocaine for correction of temple hollowing in 
Chinese population
Rationale: JUVÉDERM® VOLUMA® with Lidocaine (hereafter, VOLUMA with Lidocaine) is 
a temporary HA filler that is a structural gel developed specifically to provide a safe, minimally
invasive method to create and restore facial volume. This protocol is designed as a pivotal study 
to collect safety and effectiveness data on VOLUMA with Lidocaine for correction of temple 
hollowing in Chinese patients in order to support NMPA approval for such intended use.
Objectives and Endpoints
The objectives of this study are to evaluate the safety and effectiveness of VOLUMA with 
Lidocaine injectable gel in adult participants seeking correction of temple hollowing.
Objectives
Endpoints
Effectiveness
To evaluate the 
effectiveness of 
VOLUMA with 
Lidocaine 
injectable gel in 
adult participants 
seeking 
correction of 
temple hollowing
Primary
Responder status based on the Evaluating Investigator’s (EI’s) live 
assessment of temple hollowing using ATHS at Month 6 after last 
treatment for treatment group and after randomization for control group. 
Secondary
Responder status based on the EI’s assessment of the temple area using 
GAIS at Month 6 after last treatment for treatment group and after 
randomization for control group.
Responder status based on the participant’s assessment of the temple area 
using GAIS at Month 6 after last treatment for treatment group and after 
randomization for control group.
Change from baseline on FACE-Q Satisfaction with Facial Appearance 
questionnaire at Month 6 after last treatment for treatment group and after 
randomization for control group.
Change from baseline on FACE-Q Satisfaction with Temples questionnaire 
at Month 6 after last treatment for treatment group and after randomization 
for control group.
Safety
To evaluate the 
safety of 
VOLUMA with 
Lidocaine 
injectable gel in 
adult participants 
seeking 
correction of 
temple hollowing

Participant assessment of procedural pain

Participant assessment of ISRs

AEs

Jaw Functional Limitation Scale

Vital signs
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Overall Design

Multicenter, randomized, controlled, parallel-design study in participants with minimal,
moderate, or severe temple hollowing (Grade 2, 3, or 4 on the ATHS)

Single-blind: EIs are blinded; treating investigators (TIs) and participants are not blinded

VOLUMA with Lidocaine injected with 27 G 1/2” or 25 G 1” needles to the 
supraperiosteal plane in the temple area (up to 3 mL per temple for initial and touch-up 
treatments combined) for the treatment group and delayed treatment for the control group
Disclosure Statement: This is a parallel-design treatment study with 2 arms that is blinded to 
EIs.
Number of Participants:
168 participants will be randomized (112 treatment group, 56 control group) to achieve 
135 evaluable participants (90 treatment group, 45 control group) at the Month 6 primary
timepoint.
Intervention Groups and Duration:

Participants will be randomized in a 2:1 ratio of treatment group to control group.
Screening period is up to 30 days for all participants.

Treatment group participants receive initial treatment and optional touch-up treatment at 
1 month if the TI thinks that optimal correction has not been achieved and agreed upon by 
both the participant and TI. Telephone calls to assess safety will be made 3 days after each 
treatment, and follow-up visits will occur at Months 1, 3, 6, 9, and 12 after last treatment. 

Control group participants are followed for 6 months after randomization (no-treatment 
control period) and then either exit the study or receive optional treatment (initial and 
touch-up, if needed) in the post-control period. Telephone calls to assess safety will be 
made 3 days after each treatment, and follow-up visits will occur at Months 1, 3, and 6
after last treatment. 
Data Monitoring Committee: No
Protocol modifications due to travel restrictions or other pandemic or natural disaster-
related reasons: 
During the course of the study, should it ever become necessary to remain home or to shelter-in-
place per local, regional, or state orders, the sponsor will engage with study site staff in efforts to 
ensure the safety of participants, maintain protocol compliance, and minimize risks to the 
integrity of the study while trying to best manage participant continuity of care. This may include 
alternative methods for assessments (eg, phone contacts or virtual site visits) or alternative 
locations for safety data collection in agreement with the sponsor. In all cases, these alternative 
measures must be allowed by local regulations and permitted by IEC. Investigators should notify
the sponsor if any urgent safety measures are taken to protect the participants against any 
immediate hazard.
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Note: If the participant is not able to present in-clinic to the site due to national or regional travel restrictions, site closure as a 
result of these restrictions, or a participant declines an in-clinic visit due to pandemic or natural disaster-related health 
concerns, a telephone or virtual visit is permitted. However, if a participant is later able to present in-clinic to the site within 
the visit window, assessments may be performed in-clinic and the data will be captured for the visit. 
a
All follow-up visits are scheduled from the date of the last treatment: If no touch-up treatment is performed, initial 
treatment will also be the last treatment.
b
All study exit procedures are to be performed for participants who withdraw from the study.
c
All screening procedures (including pregnancy test) must be performed before randomization; randomization must occur 
before initial treatment.
d
For female participants of childbearing potential; administered and confirmed negative before randomization or study 
intervention. Pregnancy testing need not be repeated if study pregnancy testing has been conducted within 7 days before 
randomization/initial treatment. In post-control period to be conducted only at study exit visit. A female participant is not 
considered of childbearing potential if she has been postmenopausal for at least 1 year or does not have a uterus at the time 
of study entry. Can be urine or blood pregnancy test according to site requirements.
e
The TI may perform a touch-up treatment if agreed upon by both the participant and TI. Touch-up treatment is 
recommended if the TI thinks that optimal correction has not been achieved.
f
Must be completed before randomization.
g
Must be completed before study interventions.
h
Performed at Month 6 visit only.
i
If participants exit the study before Month 6, then lab testing is needed at Exit Visit.
j
The 30-day daily safety diaries are to be completed following each treatment starting on the day of treatment and are 
considered complete if all days are completed until the visit 1 month after treatment.
k
Assessment on Day 14 after each treatment will be recorded along with safety diaries, while for other visits it will be 
performed on-site.
l
Performed at Month 1 visit only.
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Note: If the participant is not able to present in-clinic to the site due to national or regional travel restrictions, site 
closure as a result of these restrictions, or a participant declines an in-clinic visit due to pandemic or natural 
disaster-related health concerns, a telephone or virtual visit is permitted. However, if a participant is later 
able to present in-clinic to the site within the visit window, assessments may be performed in-clinic and the 
data will be captured for the visit.  
a
During the control period all follow-up visits are scheduled from the date of randomization. 
b
During the post-control period, all follow-up visits are scheduled from the date of the optional last treatment: 
If no touch-up treatment is performed, optional initial treatment will also be the optional last treatment.
c
All screening procedures (including pregnancy test) must be performed before randomization; randomization 
must occur before initial treatment.
d
For female participants of childbearing potential; administered and confirmed negative before randomization 
or study intervention. Pregnancy testing need not be repeated if study pregnancy testing has been conducted 
within 7 days before randomization. Pregnancy testing to be conducted only at treatment visits and study exit 
visit. A female participant is not considered of childbearing potential if she has been postmenopausal for at 
least 1 year or does not have a uterus at the time of study entry. Can be urine or blood pregnancy test 
according to site requirements.
e
Must be completed before randomization.
f
Must be completed before study interventions.
g
The TI may perform a touch-up treatment if agreed upon by both the participant and TI. Touch-up treatment 
is recommended if the TI thinks that optimal correction has not been achieved.
h
Performed at Month 6 after last treatment only. If participants exit the study after last treatment in the post-
control period, then laboratory testing is needed at Exit Visit.
i
The 30-day daily safety diaries are to be completed following each treatment starting on the day of treatment 
and are considered complete if all days are completed until the visit 1 month after treatment.
j
Assessment on Day 14 after each treatment will be recorded along with safety diaries, while for other visits it 
will be performed on-site.
k
Performed at Month 1 visit only.
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2.
Introduction
JUVÉDERM® VOLUMA® with Lidocaine (hereafter, VOLUMA with Lidocaine) is a temporary
HA filler that is a structural gel developed specifically to provide a safe, minimally invasive 
method to create and restore facial volume. VOLUMA with Lidocaine has an HA concentration 
of 20 mg/mL, which has been shown to provide volumizing properties in the restoration of 
mid-face volume (Jones 2013), and it is expected to provide similar results when used to 
volumize the temporal fossa for the correction of temple hollowing.
VOLUMA with Lidocaine is a sterile, biodegradable, nonpyrogenic, viscoelastic, clear, 
colorless, homogenized, HA gel implant (dermal filler). The HA is produced by
Streptococcus species of bacteria and is mixed with phosphate buffer and crosslinked by adding 
a minimum amount of BDDE to form a 3D HA gel. The HA concentration is 20 mg/mL, and 
0.3% w/w lidocaine hydrochloride is added to enhance participant comfort. Additional 
information about VOLUMA with Lidocaine is provided in the IB.
2.1.
Study Rationale
VOLUMA with Lidocaine is specifically designed for volumizing and has demonstrated 
effectiveness in restoring age-related volume deficit to the mid-face (Jones 2013). 
VOLUMA with Lidocaine received the CE mark in 2008 to restore volume of the face and 
received FDA approval in 2013 for correction of age-related volume deficit in the mid-face. It is 
currently being used in Europe to restore volume to the temple area, among other areas of the 
face.
In a recent open-label, single-site study involving 30 participants, Baumann (2019) showed that 
VOLUMA with Lidocaine can be safely and effectively used to treat temple hollowing. 
However, further evidence collected under a more rigorous study design is required to fully 
characterize the safety and effectiveness of VOLUMA with Lidocaine for treating temple 
hollowing. This protocol is designed as a pivotal study to collect safety and effectiveness data on 
VOLUMA with Lidocaine for correction of temple hollowing in Chinese patients in order to 
support NMPA approval for such intended use.
2.2.
Background
Temple hollowing can have several different causes. As the face ages, multiple layers of the 
temple (defined as the area bounded by the superior temporal line, the frontal process of the 
zygomatic bone, and the zygomatic arch) are affected, which results in a loss of the convex curve 
of the temple. The changes include an increased concavity of the temporal bone, decreased 
volume of the temporalis muscle, and decreased size of the temporal fat pad (Sykes 2009). In 
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addition to aging, temple hollowing can also occur in patients with HIV and antiretroviral 
lipoatrophy (Rose 2013, Ross 2010). A coronal incision used to provide surgical exposure to the 
anterior and lateral craniofacial skeleton can also result in temple hollowing (Kim 2005).
Regardless of the cause of temple hollowing, the loss of volume in the temple area results in 
bony margins (the zygomatic arch below and the temporal line medially) that appear more 
prominent and a face that appears more skeletonized (Moradi 2011, Sykes 2009).
Treatments for temple hollowing have included surgical implants (eg, Mersilene mesh and 
calcium hydroxylapatite cement) to elevate the temporalis muscle and overlying tissues 
(Atherton 2010, Gosain 1997) and the placement of titanium mesh to create a new surface 
contour (Guo 2012). However, because of the significant risks that are associated with these 
procedures, they have been reserved for severe cases of temple hollowing where a large volume 
correction or significant contouring is needed.
For less severe cases of temple hollowing, where a smaller volume correction is needed, 
HA fillers provide a better treatment option due to the simple treatment procedure, predictable 
results, and proven safety record. Several studies have described the use of HA-based soft-tissue 
fillers to successfully treat temple hollowing.
Baumann (2019) conducted an open-label, single-site US study of 30 participants to examine the 
use of VOLUMA with Lidocaine in the treatment of temple hollowing. A total of 98% of 
participants had long-lasting (12 months) results and high patient satisfaction. Most participants 
perceived themselves as looking younger than at baseline. After initial treatment (but not 
touch-up treatment), mild to moderate self-limited jaw pain was noted by 40% (12/30) of the 
participants during mastication. The investigator reported that all other AEs were consistent with 
what may be expected by an HA filler. Headache was reported by a third of the participants.
Ueland (2019) conducted a prospective, comparative study of the safety and effectiveness of 
VOLUMA with Lidocaine versus autologous fat for treatment of temple hollowing after lateral 
orbital wall decompression in thyroid eye disease. Of the 29 participants, 17 were treated 
bilaterally with VOLUMA with Lidocaine in the right temple and autologous fat in the left 
temple, and 12 were treated unilaterally (5 VOLUMA with Lidocaine and 7 autologous fat).
Photographs scored by 3 investigators on a 3-point temporal hollowing scale showed better 
results for VOLUMA with Lidocaine through 2 years (p < 0.001). Soft tissue thickness as 
measured by ultrasound also showed a significantly greater increase for VOLUMA with 
Lidocaine through 2 years (p = 0.005). The most common complications for VOLUMA with 
Lidocaine were bruising, irregular surface, and swelling that resolved without treatment.
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2.3.
Benefit/Risk Assessment
The injection procedure, anesthetic agents, or VOLUMA with Lidocaine may cause some of the 
risks and/or discomforts listed below. Unforeseeable risks or results are also a possibility. The 
risk of developing a serious complication is small. If a complication occurs, participants will be 
advised to contact the TI who will use his/her medical judgment to do whatever is necessary to 
treat the participant.
As with any skin injection, risks can be posed by the injection procedure itself, the anesthetic 
agent, and injection of VOLUMA with Lidocaine injectable gel. Risks related to the injection 
procedure include redness, itching, pain, tenderness, swelling, bruising, and lumps and bumps, 
which are common to dermal filler injection procedures in general. The use of a small gauge 
needle to deliver VOLUMA with Lidocaine used in this study is intended to minimize tissue 
trauma. The inclusion of 0.3% lidocaine in the formulation is meant to reduce pain during the 
injection, and this needs to be taken into account when administering concomitant additional 
anesthetics as well as in relation to participants’ medical history (ie, allergy to lidocaine). Risks 
associated with the anesthetic agent include allergic reactions that may manifest as an 
anaphylactic reaction, skin rash, redness, itching, hives, burning, stinging, swelling, tenderness, 
and transient loss of skin color.
Prior to administering any topical pretreatment anesthesia, the TI will thoroughly review the 
participant’s history to confirm the suitability of the planned anesthetic agent. Additionally, the 
IDFU must be carefully reviewed, and each individual participant’s medical history must be 
carefully considered, when evaluating a potential participant’s candidacy for study enrollment.
Due to the location of the treatment area, tenderness, or pain in the jaw when chewing may be 
experienced, but it can usually be treated with acetaminophen and generally will resolve within a 
few days.
The benefit of using HA soft-tissue fillers in facial aesthetics has been documented in the 
published literature showing the safety and effectiveness of HA soft-tissue fillers. It is 
anticipated that the safety and effectiveness of temple hollowing treatment are similar to those 
identified in other studies using JUVÉDERM® products for temple hollowing and for similar 
indications such as correction of mid-face volume.
Considering a pandemic or natural disaster, the benefit and risk to participants in this study has 
been evaluated. Based on the limited information to date, no additional risk to study participants 
is anticipated with the use of VOLUMA with Lidocaine.
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More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of VOLUMA with Lidocaine may be found in the IB.
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3.
Objectives and Endpoints
The objectives of this study are to evaluate the safety and effectiveness of VOLUMA with 
Lidocaine injectable gel in adult participants seeking correction of temple hollowing.
Objectives
Endpoints
Effectiveness
To evaluate the 
effectiveness of 
VOLUMA with 
Lidocaine 
injectable gel in 
adult participants 
seeking 
correction of 
temple hollowing
Primary
Responder status based on the EI’s live assessment of temple hollowing 
using ATHS at Month 6 after last treatment for treatment group and after 
randomization for control group. 
Secondary
Responder status based on the EI’s assessment of the temple area using 
GAIS at Month 6 after last treatment for treatment group and after 
randomization for control group.
Responder status based on the participant’s assessment of the temple area 
using GAIS at Month 6 after last treatment for treatment group and after 
randomization for control group.
Change from baseline on FACE-Q Satisfaction with Facial Appearance 
questionnaire at Month 6 after last treatment for treatment group and after 
randomization for control group.
Change from baseline on FACE-Q Satisfaction with Temples questionnaire 
at Month 6 after last treatment for treatment group and after randomization 
for control group.
Other
Responder status based on the EI’s live assessment of temple hollowing 
using ATHS at specific scheduled visits. 
Responder status based on the EI’s assessment of the temple area using 
GAIS at specific scheduled visits.
Responder status based on the participant’s assessment of the temple area 
using GAIS at specific scheduled visits.
Change from baseline on FACE-Q Satisfaction with Facial Appearance 
questionnaire at specific scheduled visits.
Change from baseline on FACE-Q Satisfaction with Temples questionnaire 
at specific scheduled visits.
Treatment satisfaction questions (include following items) at specific 
scheduled visits:
Participant satisfaction with treatment;
Participant satisfaction with how natural the effects of the treatment feel;
Participant satisfaction with how natural the effects of the treatment look;
Participant response on the treatment meeting expectation;
Participant response on interest to continue to use the treatment;
Participant response on willingness to recommend treatment to a friend.
Participant response to the participant’s self-perception of age at specific 
scheduled visits.
Temple volume change as assessed on 3D image volumetric analysis at 
specific scheduled visits.
Safety
To evaluate the 
safety of 
VOLUMA with 
Lidocaine 
injectable gel in 
adult participants 
seeking 
correction of 
temple hollowing

Participant assessment of procedural pain

Participant assessment of ISRs

AEs

Jaw Functional Limitation Scale

Vital signs
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4.
Study Design
4.1.
Overall Design
This is a prospective, multicenter, evaluator-blinded, randomized, parallel-group, no-treatment 
controlled study to evaluate the safety and effectiveness of VOLUMA with Lidocaine HA 
injectable gel to correct temple hollowing. 
The study will involve up to 9 investigational sites. The study population is represented by
Chinese adults who are seeking correction of temple hollowing and who meet the study criteria 
according to the study design.
Participants will be randomized in a 2:1 ratio of treatment group to control group.
Participants will stay in the study for up to 14 months depending on their randomization group. 
For the treatment group, each participant will be in the study for up to 14 months: up to 1 month 
for screening, up to 30 days of treatment, and up to 12 months of follow-up after last treatment. 
For the control group, each participant will be in the study for 7 months (up to 1 month for 
screening and 6 months for follow-up) and then may exit or opt to receive study intervention. 
Control participants who opt to receive study intervention will be in the study for an additional 
7 months (up to 30 days for treatment and 6 months of follow-up), for a total of 14 months.
The study will compare the treatment to no treatment, with the primary timepoint set at Month 6 
(for treatment group, 6 months after last treatment; for control group, 6 months after 
randomization). Each site will have a PI who is responsible for the overall conduct of the study at 
that site and may also serve as the TI. The TI performs all study treatments and safety 
assessments, and the blinded EI evaluates ATHS and GAIS.
The study design is single-blind where the EIs and image analysis technicians will remain 
blinded to each participant’s assigned study intervention throughout the course of the study. The 
PIs/TIs, study coordinators, and participants will not be blinded to treatment, and they will 
secure the randomization and other records (eg, records of study treatments and prior study 
assessments) from potential discovery by the blinded EIs. The TIs will not discuss the 
randomized treatment assignments with or in the presence of the EIs. Additional precautions to 
keep blinding are outlined in Section 6.3.
During the course of the study, should it ever become necessary to remain home or to shelter-in-
place per local, regional, or state orders, the sponsor will engage with study site staff in efforts to 
ensure the safety of participants, maintain protocol compliance, and minimize risks to the 
integrity of the study while trying to best manage participant continuity of care. This may include 
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alternative methods for assessments (eg, phone contacts or virtual site visits) or alternative 
locations for safety data collection in agreement with the sponsor. In all cases, these alternative 
measures must be allowed by local regulations and permitted by IEC. Investigators should notify
the sponsor if any urgent safety measures are taken to protect the participants against any 
immediate hazard.
4.2.
Scientific Rationale for Study Design
4.2.1.
Participant Input into Design
The design elements of this protocol have been reviewed with patients/patient partners to obtain 
their perspectives in the following areas: schedule of events, parameter invasiveness, frequency
of parameter compared to standard of care, length of study and visits, how study drug is 
administered or how device is being used.
4.2.2.
No-treatment Control
The no-treatment control was chosen primarily because no HA filler is currently
NMPA- -approved for use in correction of temple hollowing; therefore, an active comparator 
design is not possible. A sham injection (eg, saline) was not chosen as a control because it is 
easily distinguished from a soft-tissue filler injection by both the injector and participant, and, 
therefore, does not result in any additional blinding over a no-treatment control. Meanwhile, a 
sham injection exposes control participants to the pain associated with facial injections and puts 
them at risk for infection or ISRs with no clinical benefit.
While surgical options to treat temple hollowing are available, they are not appropriate controls 
for a soft-tissue filler injection. The risks associated with these surgical procedures are much 
higher than the risks of a soft-tissue filler treatment. Likewise, the amount of correction that can 
be achieved with a surgical procedure and a soft-tissue filler differ. Because of these differences, 
the participant populations appropriate for treatment with soft-tissue fillers and surgical 
treatments are not the same. The differences would make randomization difficult and would 
confound any comparisons with the study intervention.
4.2.3.
Evaluator Blinded
Because the control group uses a no-treatment design, it is not possible to blind the TI or 
participant to treatment. Therefore, a blinded EI will perform effectiveness assessments to reduce 
the bias associated with these assessments.
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4.2.4.
Allergan Temple Hollowing Scale
Photonumeric scales have become a standard for assessing the results of soft-tissue filler 
treatments worldwide. The ATHS is a 5-point ordinal scale developed by Allergan to grade the 
severity of temple hollowing. The ATHS contains a morphed photograph showing all 5 severities 
of temple hollowing as well as photographic images of participants representing different 
Fitzpatrick skin types, race categories, both sexes, and all 5 severities of temple hollowing 
(0 = Convex, 1 = Flat, 2 = Minimal, 3 = Moderate, 4 = Severe).
A scale validation study (Carruthers 2016, Study FSV-001) was conducted to assess the inter-
and intra-rater reliability of the ATHS. Each of the 8 trained clinicians independently evaluated 
the participants in person and assigned each participant an ATHS grade based on the live 
evaluation. Three weeks later, the same 8 trained clinicians re-evaluated the same participants 
and assigned each participant an ATHS grade based on the live evaluation and without reliance 
on prior memory. Both the inter- and intra-rater agreement were substantial (> 0.60), indicating 
substantial agreement among the raters as well as within the raters between the 2 in-clinic
evaluation sessions, respectively. Additionally, the results demonstrated that a 1-point difference 
or higher is clinically significant. Therefore, results confirmed that the ATHS is validated and 
appropriate to be used as a primary effectiveness measure for this study.
4.2.5.
FACE-Q Questionnaire
Patient-reported outcomes are being more often used in clinical research to provide insight on the 
results of the study intervention from the participant’s perspective. The FACE-Q Satisfaction 
with Facial Appearance scale was developed to provide highly reliable, valid, and responsive 
participant assessments. The scale has strong psychometric properties and the potential to 
provide clinically meaningful scores (Pusic 2013). The current version of the FACE-Q 
Satisfaction with Temples scale is based on existing qualitative research to assess satisfaction in 
the temple area. The scale developers will conduct additional research to assess the psychometric 
properties of the scale, finalize the list of questions, and create the scoring algorithm.
4.3.
Justification for Dose
The volume of VOLUMA with Lidocaine to be injected for each participant will be determined 
by the TI and will take into consideration the participant’s degree of temple hollowing, the 
desired outcome, and the need to maintain balance and proportion with other facial features.
In the study conducted by Baumann (2019) with VOLUMA with Lidocaine, participants could 
receive up to 2 mL per temple for their initial injection and a maximum of 3 mL per temple for 
initial and touch-up treatment combined. In the Ueland (2019) study, participants received a 
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maximum of 2 mL in a single temple treated with VOLUMA with Lidocaine. Based on these 
studies, the maximum allowable injection volume for this study was set at 3 mL in each temple 
for initial and touch-up combined, with a 2 mL maximum allowable volume per temple per 
treatment session. 
For investigational use in this clinical study, the study intervention will be injected deeply
(supraperiosteal plane) with the supplied 27 G 1/2” or 25 G 1” needles to correct temple 
hollowing. The technique specified for this study is selected because it is a safe and 
easy -to -follow method for injection (Breithaupt 2015, Sykes 2015). The detailed recommended 
injection technique is provided in the IDFU and IB.
4.4.
End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
Treatment group participants will be considered completers if they complete the Month 12 after 
last treatment visit. Control group participants will be considered completers if they complete the 
Month 6 after randomization visit and do not receive optional treatment or if they complete the 
Month 6 after optional last treatment visit.
There are no pandemic or natural disaster-related protocol modifications for the Study Exit Visit. 
If the participant is not able to present in-clinic to the site due to national or regional travel 
restrictions, site closure as a result of these restrictions, or a participant declines an in-clinic visit 
due to pandemic or natural disaster-related health concerns, the participant will be asked to 
return to the site at a later time. Once the participant is able to present in-clinic to the site, 
assessments will be performed in-clinic and the data will be captured for the visit. 
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5.
Study Population
Chinese adults with temple hollowing who are seeking restoration in the temple area.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
1.
Age
1.01
Participant must be 18 or over, at the time of signing the ICF
2.
Sex
2.01
Male or female
3.
Type of Participant and Temple Hollowing Characteristics
3.01
Participants seeking improvement of temple hollowing
3.02
Has Minimal, Moderate, or Severe temple hollowing (Grade 2, 3, or 4 on the ATHS) for each temple on 
EI live assessment (both temples must qualify but do not need to have the same score)
4.
Informed Consent
4.01
Capable of giving signed informed consent which includes compliance with the requirements and 
restrictions listed in the ICF and in this protocol
4.02
Written informed consent from the participant has been obtained prior to any study-related procedures
4.03
Written documentation has been obtained in accordance with the relevant country and local privacy 
requirements, where applicable
5.
Other
5.01
Able, as assessed by the TI, and willing to follow study instructions (including compliance with the 
safety diary) and likely to complete all required study visits
5.02
Is able to complete effectiveness self-assessments without the use of glasses (contact lens use is 
acceptable if they will be used for all participant self-assessments)
5.03
Participant must be in good health as determined by medical history, physical examination, vital signs, 
and investigator’s judgment, including no known active pandemic infection.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1.
Medical Conditions
1.01
The participant cannot achieve at least a 1-grade improvement for each temple from the EI’s baseline 
score on the ATHS given the allowed injection volume, in the opinion of the TI
1.02
Has temple hollowing due to trauma, congenital malformations, or lipodystrophy, either congenital or 
acquired
Additional examples include: congenital myotonic dystrophy, HIV-associated lipodystrophy, or acquired 
generalized lipodystrophy
1.03
Has experienced trauma to the temple area within 6 months before enrollment or has residual 
deficiencies, deformities, or scarring
1.04
Atrophic skin in the temple area that might not be suitable for injection, in the opinion of the TI
1.05
Temporal arteritis or history of temporal arteritis
1.06
Temporomandibular joint dysfunction or any other jaw issues
1.07
Recurrent temporal headaches such as temporal tendonitis migraine
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1.08
Tendency to develop hypertrophic scarring
1.09
Active autoimmune disease
1.10
History of anaphylaxis or allergy to lidocaine (or any amide-based anesthetics), HA products, or 
Streptococcal protein
1.11
Current cutaneous or mucosal inflammatory or infectious processes (eg, acne, herpes), abscess, an 
unhealed wound, or a cancerous or precancerous lesion, above the subnasale
2.
Prior/Concomitant Therapy
2.01
Prior facial reconstructive surgeries, face-lift, or brow lift as well as surgeries on the temple area 
(eg, biopsy)
2.02
Fat injection or permanent facial implants (eg, polymethylmethacrylate, silicone, 
polytetrafluoroethylene) in the temple area 
2.03
Fat injection or permanent facial implants (eg, polymethylmethacrylate, silicone, 
polytetrafluoroethylene) in facial areas other than the temples within 12 months before enrollment
2.04
Semipermanent soft-tissue filler treatment (eg, calcium hydroxylapatite, poly-L-lactic acid) in the temple 
or mid-face within 36 months before enrollment
2.05
Temporary dermal filler injections above the subnasale within 12 months before enrollment
2.06
Temporary dermal filler injections in the nasolabial fold or below the subnasale within 3 months prior to 
enrollment
2.07
Botulinum toxin treatment above the subnasale or at masseter muscle within 6 months before enrollment 
2.08
Mesotherapy or cosmetic facial procedures above the subnasale within 6 months before enrollment
Examples of mesotherapy or cosmetic facial procedures are laser, photomodulation, intense pulsed light, 
radio frequency, dermabrasion, moderate or greater depth chemical peel, or other ablative procedures
2.09
Has braces or other orthodontics 
2.10
Changes in use of over-the-counter or prescription oral or topical, antiwrinkle products above the 
subnasale within 30 days before enrollment or planned changes during the study
Participants are not eligible for this study if they have begun using any new over-the-counter or 
prescription oral or topical, antiwrinkle products above the subnasale within 30 days before enrollment. 
Participants 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
2.11
Is on a regimen of anticoagulation therapy (eg, warfarin, clopidogrel)
3.
Prior/Concurrent Clinical Study Experience
3.01
Current enrollment in an investigational drug or device study or participation in such a study within 
30 days of entry into this study
4.
Diagnostic Assessments
4.01
Abnormal and clinically significant results on hematology, clinical chemistry, or urinalysis, which
according to the TI or designee will have impact to study treatment, evaluation and outcome.
5.
Other Exclusions
5.01
Has tattoos, piercings, facial hair, or scars above and including the subnasale that would interfere with 
visual assessment of the temple
5.02
Females who are pregnant, nursing, or planning a pregnancy
5.03
TI’s discretion based on participant’s safety and/or study integrity
The participant has a condition or is in a situation that, in the TI’s opinion, may put the participant at 
significant risk, may confound the study results, or may interfere significantly with the participant’s 
participation in the study
5.04
Directly or indirectly involved in the conduct and administration of this study
Directly or indirectly involved in the conduct and administration of this study as an investigator, 
subinvestigator, study coordinator, or other study staff member; employee of the sponsor; first-degree 
family member, significant other, or relative residing with one of the above persons involved directly or 
indirectly in the study; or enrolled in the study at another clinical site
5.05
Plans a significant weight change (more than 10% of body weight) during the study
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5.3.
Lifestyle Considerations
Within the first 24 hours after study intervention, it is recommended that participants avoid 
strenuous exercise, extensive sun or heat exposure, and alcoholic beverages. Exposure to any of 
the above may cause temporary redness, swelling, and/or itching at the injection sites.
For 2 days after study intervention, it is recommended that participants avoid unnecessary
external compression of the treatment site that could cause displacement or indentation where the 
product has been placed. Participants will be advised not to have a massage, enter a hot spring or 
sauna, receive excessive sun exposure, or go swimming during the week following any study 
intervention.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomized/treated. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, including reason for screen 
failure, eligibility criteria, and any SAEs.
Individuals who do not meet the criteria for participation in this study (screen failures) may not 
be rescreened.
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6.
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to the 
study protocol.
Participants may undergo a touch-up treatment 30 days after the initial treatment if agreed upon 
by both the participant and TI. See Section 6.6.1 for details.
6.1.
Study Intervention Administered
Table 6-1
Study Interventions
Device
VOLUMA with Lidocaine
Dose Formulation
20 mg/mL HA crosslinked with BDDE + 0.3% lidocaine (w/w gel)
Route of 
Administration 
Deep injection (supraperiosteal plane), injected with a 27 G 1/2” or 25 G 1” needle in 
the temple area
Model and 
Specification
Study intervention will be provided in prefilled 1 mL syringes. Each syringe will be 
packaged with 27 G 1/2” needles for injection in a thermoform blister. Two blisters will 
be packaged in a kit. Each kit and thermoform blister will be labeled as required per 
country requirements. The 25 G 1” needles will be provided separately.
Manufacturer
Allergan
Route de Promery
Zone Artisanale de Pré-Mairy
Pringy 74370, Annecy, France
Number and 
Timing of 
Interventions
Treatment group: 
Day 1: Initial treatment
Month 1 after initial treatment: Optional touch-up
Control group (optional):
Month 6 after randomization: optional initial treatment
Month 1 after optional initial treatment: optional touch-up
Volume Per 
Intervention
Initial and touch-up combined: up to 3 mL/temple 
Any single treatment: up to 2 mL/temple
Immediately before dispensing the study intervention, the investigator (or appropriately trained 
designee) will write the participant identification number and the date on the label.
6.1.1.
Medical Devices
The Allergan-manufactured medical device provided for use in this study is VOLUMA with 
Lidocaine (copackaged with needles, see Table 6-1). Instructions for medical device use are 
provided in the IDFU and IB.
All device deficiencies (including malfunctions, use error, and inadequate labeling) shall be 
documented and reported by the PI/TI throughout the clinical investigation (see Section 8.3.6)
and appropriately managed by the sponsor.
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6.1.2.
Instructions for Use and Administration
For investigational use in this clinical study, VOLUMA with Lidocaine must be injected 
supraperiosteally following a specified injection technique to obtain optimal correction of temple 
hollowing and aesthetic improvement with minimal safety concern. Study intervention is limited 
to the temple area. The 27 G 1/2” or 25 G 1” needles supplied with the investigational product 
must be used.
The TIs must be experienced in the use and administration of HA implants and be practicing in 
the field of aesthetic medicine, plastic/cosmetic/reconstructive surgery, or dermatology. Before 
the study begins, the TIs will receive training in the administration of VOLUMA with Lidocaine 
according to the technique specified for this study. This injection technique is selected since this 
is a safe and easy-to-follow method for injection (Breithaupt 2015, Sykes 2015).
Anesthesia (ice, topical anesthesia, or local injectable anesthesia) may be administered per the 
TI’s standard practice but must be limited to the treatment area. 
The TIs will use aseptic injection technique, and the following procedures must be used to ensure 
participant safety. 

Determine up to 3 injection sites and mark.

Inspect and palpate injection sites to identify the location of any superficial vessels, 
including the superficial temporal artery, and avoid injecting into any vessels.

Insert the needle at the marked points at an 85° to 90° angle to the plane of the temple 
until it reaches the periosteum.

If resistance is felt before reaching the periosteum, withdraw and re-orient the needle.

Before injection, attempt to aspirate the needle. If blood is observed, withdraw and 
re-orient the needle.

Inject VOLUMA with Lidocaine into the treatment area slowly using gentle, even 
pressure on the syringe.

Stop injecting immediately if any resistance is felt or if the participant complains of severe 
pain.
If a vessel occlusion occurs, stop the injection. Treat in accordance with American Society for 
Dermatologic Surgery guidelines or the Chinese Society of Aesthetic and Plastic Doctor 
guidelines, which include hyaluronidase injection (Alam 2008, Breithaupt 2015,
Carruthers 2015, Minimally invasive Anti-aging Committee 2015). 
The detailed recommended injection technique is provided in the IDFU and IB.
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6.2.
Preparation/Handling/Storage/Accountability
1. The PI or designee must confirm appropriate temperature conditions have been 
maintained during transit and pretreatment storage for all study interventions and ensure 
any discrepancies are reported and resolved before use of the study intervention.
2. Only participants enrolled in the study may receive study intervention, and only the TI 
may administer study intervention. All study interventions must be stored in a secure, 
environmentally controlled, and temperature monitored (automated) area in accordance 
with the labeled storage conditions with access limited to the PI/TI and authorized site 
staff.
3. The PI (or a delegated designee) is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final disposition 
records). Include participant identification number, device serial or lot number, and date of 
treatment.
4. Further guidance and information for the final disposition of unused study intervention are 
provided in the Study Site Binder. 
5. Devices that are damaged during shipment or at the site or that malfunction during use 
(eg, faulty syringe or plunger) must be accounted for and returned. The PI will promptly
notify the sponsor’s Clinical Research department of any device malfunction. The Clinical 
Research or Product Support representative will provide instruction for the return of any
faulty syringe for evaluation.
6.3.
Measures to Minimize Bias: Randomization and Blinding
Prior to initiation of study intervention, each consented participant will be assigned a participant 
number that will be recorded on the appropriate eCRF. At the time of randomization (ie, at the 
Randomization/Initial Treatment visit), eligible participants will be randomly assigned at a 
2:1 ratio to treatment group or control group. For all treatments, the right side will be treated 
first. Randomization will be within each study site. All participants will be centrally randomized 
using an IWRS. Before the study is initiated, the log-in information and directions for the IWRS 
will be provided to each site. 
Study intervention will be injected at the study visits summarized in the SoA (Section 1.3). 
Instructions for preparing and administering the study intervention are provided in the IDFU and 
IB.
If participants are withdrawn, they will not be replaced. 
The EIs and image analysis technicians will remain blinded to each participant’s assigned study 
intervention throughout the course of the study. The PIs/TIs, study coordinators, and participants 
will not be blinded to treatment, and they will secure the randomization and other records 
(eg, records of study interventions and prior study assessments) from potential discovery by the 
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blinded EI. The TIs will not discuss the randomized treatment assignments with or in the 
presence of the EIs.
In order to maintain the blind, the EI will not be present during any treatment visits and will not 
have access to any unblinding information (such as treatment eCRFs or device accountability
logs). In addition, participants will be instructed not to discuss whether they have received 
treatment with the EI. Image analysis technicians will only have access to image files that will 
not contain any unblinding information (such as randomization status or visit name).
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the sites to verify that randomization/dispensing has been done 
accurately.
The EI must remain blinded throughout the study. If a participant requires immediate medical 
attention by an unblinded physician, this must be provided by the TI whenever possible. In the 
event that no unblinded physician is available to provide such treatment, the investigational site 
or sponsor staff may break the blind so that the EI can provide treatment.
Instructions for preparing the study intervention are provided in the IDFU and IB.
Design bias in this study is reduced through the use of a randomized control group, a blinded EI 
to assess effectiveness results, and the inclusion of objective measures of temple volume that are 
determined by a blinded image analysis technician.
6.4.
Study Intervention Compliance
Study intervention compliance is not applicable because the TI administers the study
intervention. The study site will keep an accurate record that specifies the amount of study
intervention administered to each participant and the date of administration.
6.5.
Concomitant Therapy
The use of any concomitant procedure or medication, prescription or over-the-counter, is to be 
recorded on the participant’s eCRF at each visit along with the reason the therapy is taken.
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Any procedure/surgery, medication or vaccine (including over-the-counter, prescription 
medicines, vitamins, herbal supplements, or other specific categories of interest) that the 
participant is receiving at the time of enrollment or receives during the study must be recorded 
along with:

Indication

Dates of administration including start and end dates

Dosage information including dose and frequency
At screening and study exit and at each contact with the participant (by phone or in person), 
study site staff will question each participant specifically on the use of concomitant medications. 
Study site staff must notify the sponsor immediately if a participant receives any concomitant 
medications not permitted by the protocol.
6.5.1.
Rescue Medicine
Rescue medicine is not applicable.
6.5.2.
Prohibited Therapy and Washout Before the Study
Participants must discontinue any of the medications listed in Table 6-2 for the specified period 
prior to baseline. These medications are prohibited for the duration of the study. Other 
medications being used at screening may be continued.
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Table 6-2
Required Washout Intervals for Prohibited Therapy Prior to Baseline
Washout Period
Medication or Procedure
10 days 
Ongoing regimen of medications and/or substances known to increase coagulation time 
(eg, aspirin, ibuprofen, or herbal supplements)
NOTE: The 10-day washout period must continue for 3 days after study intervention (initial 
and touch-up) is administered
30 days 
Any investigational product
Any new over-the-counter or prescription oral or topical, antiwrinkle products above the 
subnasale
3 months
Temporary dermal filler injections in the nasolabial folds or below the subnasale
6 months
Botulinum toxin injections above the subnasale or at masseter muscle
Mesotherapy or cosmetic facial procedures (eg, laser, photomodulation, intense pulsed 
light, radio frequency, dermabrasion, moderate or greater depth chemical peel, or other 
ablative procedures) above the subnasale
12 months
Temporary dermal filler injections above the subnasale
Fat injection or permanent facial implants (eg, polymethylmethacrylate, silicone, 
polytetrafluoroethylene) in facial areas other than the temples
36 months
Semipermanent dermal filler treatment (eg, calcium hydroxylapatite, poly-L-lactic acid) in 
the temple or mid-face
6.5.3.
Permitted Interventions
All interventions are permitted except those listed as prohibited in Section 6.5.4. Topical or 
injectable anesthesia may be used during treatment according to routine practice, but it must be 
limited to the treatment areas only.
Therapy considered necessary for the participant’s welfare may be given at the discretion of the 
investigator. If the permissibility of a specific medication/intervention is in question, please 
contact the sponsor.
The sponsor or designee is to be contacted if there are any questions regarding concomitant or 
prior therapy.
6.5.4.
Prohibited Interventions During the Study
Participants must abstain from the following interventions from before the start of study
intervention until completion of the follow-up visits:

Other investigational product

Botulinum toxin injections above the subnasale or at masseter muscle
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
Mesotherapy or cosmetic facial procedures (eg, face-lift, brow lift, facial reconstructive 
surgery, surgery on the temple area [eg, biopsy], laser, photomodulation, intense pulsed 
light, radio frequency, dermabrasion, moderate or greater depth chemical peel, or other 
ablative procedures) above the subnasale

Braces or any orthodontic procedures

Permanent facial implants or fat injection

Semi-permanent dermal filler above the subnasale

Temporary dermal filler injected above the subnasale (other than study intervention)

Undergo any tattooing or piercing procedures above and including the subnasale

Allergen desensitization therapy
The following medications are prohibited or restricted throughout the study:

Hyaluronidase for aesthetic purposes (eg, to reverse overcorrection)
Participants must abstain from the following interventions from 10 days before until 3 days after 
any study intervention:

Regimen of medications or substances known to increase coagulation time (eg, aspirin, 
ibuprofen, or herbal supplements)
The decision to administer a prohibited medication/procedure during the study period is done 
with the safety of the study participant as the primary consideration. When possible, Allergan is 
to be notified before the prohibited medication/procedure is administered.
6.6.
Dose Modification
The volume to be injected will be determined by the TI, with a maximum per each temple of: 
3 mL for initial and touch-up treatments combined and a maximum of 2 mL at any treatment. 
The rationale for these volumes is discussed in Section 4.3.
6.6.1.
Retreatment Criteria
A participant may receive touch-up treatment if optimal correction has not been achieved at 
Month 1 after initial treatment for treatment group and Month 1 after optional initial treatment 
for control group, in the opinion of the TI and is agreed upon by both participant and TI.
6.7.
Intervention after the End of the Study
No study intervention will be provided after the end of the study.
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7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
A premature discontinuation will occur if a participant who signs the ICF and receives study
intervention ceases participation in the study, regardless of circumstances, before the completion 
of the protocol-defined study procedures.
Notification of early participant discontinuation from the study and the reason for 
discontinuation will be made to the sponsor and will be clearly documented on the appropriate
eCRF.
Reasons for discontinuation from the study intervention and/or the study may include the 
following commonly used or other acceptable terms:
Commonly Used Terms
Other Acceptable Terms
Adverse event
Death
Lost to follow-up
Other
Physician decision
Protocol deviation
Site terminated by sponsor
Study terminated by sponsor
Withdrawal by participant
7.1.
Discontinuation of Study Intervention
Pregnancy will discontinue a participant from receiving further study intervention. Participants 
who become pregnant and have already received a study intervention or who have been 
randomized to control group will continue in the study until all required follow-up is complete.
See the SoA (Section 1.3) for data to be collected at the time of intervention discontinuation and 
follow-up and for any further evaluations that need to be completed.
Notification of early participant discontinuation from the study and the reason for 
discontinuation will be made to the sponsor and will be clearly documented on the appropriate 
eCRF.
7.2.
Participant Discontinuation/Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon.
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
At the time of discontinuing from the study, if possible, an early discontinuation visit is to
be conducted, as shown in the SoA (Section 1.3). See the SoA (Section 1.3) for data to be 
collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed.

If the participant withdraws consent for disclosure of future information, the sponsor may
retain and continue to use any data collected before such a withdrawal of consent.

If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the PI/TI must document this in the site study records.

For any participant who withdraws from the study, the date and reason for withdrawal will 
be recorded on the eCRF. If a treatment-related AE is ongoing at the time of withdrawal, 
the TI will attempt to follow the participant until the AE has been resolved or follow-up is 
no longer possible. The PI/TI shall ask for the participant’s permission to follow his/her 
status/condition outside the study.

If a participant fails to return for 1 or more scheduled study visits, the PI/TI (or designee) 
will attempt to contact the participant to determine and document the reason the 
participant has failed to return, and to encourage compliance with the study visit schedule.

During the course of the study, it may be necessary to employ mitigation strategies to 
enable the investigator to ensure participant safety and continuity of care. Acceptable 
mitigation strategies are identified and included in Section 8.

The investigator should contact the sponsor before discontinuing a participant from the 
study for a reason other than "planned per protocol," to ensure all acceptable mitigation 
steps have been explored.
7.3.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether the participant wishes to and/or will continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls, and if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts will be documented in the participant’s 
medical record.

If the participant continues to be unreachable, he/she will be considered to have 
withdrawn from the study.
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Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 10.1.8.
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8.
Study Assessments and Procedures

Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol 
waivers or exemptions are not allowed.

Immediate safety concerns are to be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant is to continue or discontinue study
intervention.

Adherence to the study design requirements, including those specified in the SoA
(Section 1.3), is essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.

The clinical study shall not begin until the required approvals from the appropriate 
regulatory authorities and IECs have been obtained.

An unscheduled visit may occur for safety purposes (eg, evaluation of AEs or ISRs as 
requested by the participant and/or TI) or photographic reshoots, or when impacted by a 
pandemic or a natural disaster. Applicable procedures will be performed and recorded on 
the eCRF.

Throughout the study, to the extent possible, it is recommended that treatment and safety
assessments for a particular participant be performed by the same TI, and effectiveness 
assessments (ATHS and GAIS) be performed by the same EI. If it is not possible to use 
the same evaluator to follow the participant, it is recommended that evaluations overlap 
(examine the participant together and discuss findings) for at least 1 visit.

Where possible, participant questionnaires are to be completed prior to other assessments 
at each visit, with the FACE-Q questionnaires completed first and the GAIS to be 
completed last.

Safety diaries will be reviewed for potential AEs, at least at each site visit scheduled 
during the diary completion window up to the visit at which the diary is returned. 

If the participant is not able to present in-clinic to the site due to national or regional travel 
restrictions, site closure as a result of these restrictions, or a participant declines an 
in-clinic visit due to pandemic or natural disaster-related health concerns, a telephone or 
virtual visit is permitted to collect effectiveness and safety measures. The remaining visit 
assessments will be marked as not completed and the participant will be considered to 
have completed the study. However, if a participant is later able to present in-clinic to the 
site within the visit window, assessments will be performed in-clinic and the data will be
captured for the visit. 
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8.1.
Effectiveness Assessments
8.1.1.
Intervention Administration Assessments
Characteristics of the study intervention will be collected and evaluated for anesthesia usage, 
needle gauge, number of injections, volume injected, injection area, injection plane, injection 
ease, injection technique, and product moldability at all treatment visits.
Assessment
Measurement
Anesthesia usage
Method of anesthesia (topical, injectable, ice)
Anesthesia dose
Anesthesia time
Needle gauge
Inject with 27 G 1/2” or 25 G 1” needle
Number of injections
Total number of performed injections per each injection area
Injection volume
Volume injected in each injection area
Injection area
Treated areas (left temple, right temple)
Injection plane
Plane injected (supraperiosteal, other)
Injection technique
Technique used (bolus, other)
Injection ease
11-point ordinal scale: 0 = difficult, 10 = easy
Product moldability
11-point ordinal scale: 0 = stiff, 10 = moldable
8.1.2.
Primary Effectiveness Measure
The temple area of assessment was defined as the area between the temporal fusion line, the 
zygomatic arch, the lateral orbital rim, and the hairline. The primary effectiveness measure is the 
EI’s live assessment of temple hollowing, to be recorded for each temple separately, using the 
ATHS described in Table 8-1.
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Table 8-1
Allergan Temple Hollowing Scale
Score
Grade
Description
0
Convex
Rounded temple
1
Flat
Flat temple; temporal fusion line may be visible
2
Minimal
Shallow depression or concavity with minimal volume loss; temporal fusion line may be 
visible
3
Moderate
Moderate depression or concavity with moderate volume loss; moderate prominence of 
temporal fusion line
4
Severe
Deeply recessed, sunken appearance; marked prominence of temporal fusion line and 
zygomatic arch
Assessment
Timing
Measurement
ATHS
Treatment group: all on-site visits except touch-up 
treatment visit
Control group: all on-site visits except optional 
touch-up treatment visit
EI’s live assessment of temple hollowing 
using the ATHS
8.1.3.
Secondary Effectiveness Measures
There are 4 secondary effectiveness measures, to be recorded at the participant level rather than 
for each temple. The secondary effectiveness measures include independent, noncollaborative 
assessments by both the EI and the participant of global aesthetic improvement in the temple 
area using the 5-point GAIS (Table 8-2).
Table 8-2
Global Aesthetic Improvement Scale
Score
Grade
Description
2
Much Improved
Marked improvement in appearance
1
Improved
Improvement in appearance, but a touch-up or retreatment is indicated
0
No Change
The appearance is essentially the same as the original condition
-1
Worse
The appearance is worse than the original condition
-2
Much Worse
The appearance is much worse than the original condition
Participants and EIs will assess global aesthetic improvement of the temple area by comparing to 
profile view photographs taken at baseline. Participants will use a mirror to assess their current 
appearance at each visit. All participant-reported effectiveness outcomes at a visit will be 
completed before the participant sees either the TI or EI at every on-site visit except (optional) 
touch-up visit. Touch-up treatment decision is to be made before other applicable assessments.
The other secondary effectiveness measures are the participant responses on the FACE-Q 
questionnaires: Satisfaction with Facial Appearance and Satisfaction with Temples. In the 
FACE-Q Satisfaction with Facial Appearance questionnaire the responses to the 10 items will be 
summed and converted to a Rasch-transformed score that ranges from 0 to 100 (higher score 
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indicates increased satisfaction) using the algorithm developed by the FACE-Q scale developers. 
In the FACE-Q Satisfaction with Temples questionnaire, the responses to the items will be 
summed and converted to a Rasch-transformed score that ranges from 0 to 100 (higher score 
indicates increased satisfaction) using the algorithm being developed by the FACE-Q scale 
developers.
The FACE-Q scales are designed for self-completion by the participant. If a participant asks for 
clarification on or has difficulty answering a particular question on the FACE-Q questionnaires, 
investigational site staff may ask the participant to explain why he or she had difficulty 
responding or help by reading the question verbatim. Staff may not try to explain what the 
question means or rephrase the question. Instead, staff may suggest that participants must use 
their own interpretation of the question. If the participant is still unable to answer the question, 
the questionnaire can be scored with missing data.
Assessment
Timing
Measurement
Global aesthetic 
improvement of the 
temple area
Treatment group: all on-site visits 
starting from Month 1 after last 
treatment visit
Control group: Month 1, 3, 6 after 
randomization visit and Month 1, 3, 6 
after optional last treatment visit 
Single item questionnaire assessing global 
aesthetic improvement in the temple area on 
5-point ordinal scale from -2 to 2 (details in 
Table 8-2)
FACE-Q Satisfaction 
with Facial 
Appearance 
Treatment group: randomization and all 
on-site visits starting from Month 1 after 
last treatment visit
Control group: randomization and 
Month 1, 3, 6 after randomization visit 
and Month 1, 3, 6 after optional last 
treatment visit
10-item questionnaire assessing satisfaction 
with various aspects of facial appearance. 
Participants respond to each item as:
1 Very Dissatisfied
2 Somewhat Dissatisfied
3 Somewhat Satisfied
4 Very Satisfied
FACE-Q Satisfaction 
with Temples
Treatment group: randomization and all 
on-site visits starting from Month 1 after 
last treatment visit
Control group: randomization and 
Month 1, 3, 6 after randomization visit 
and Month 1, 3, 6 after optional last 
treatment visit
Multiple item questionnaire assessing 
satisfaction with various aspects of the 
temples. Participants respond to each item as:
1 Very Dissatisfied
2 Somewhat Dissatisfied
3 Somewhat Satisfied
4 Very Satisfied
Throughout the study, to the extent possible, it is recommended that treatment and safety
assessments for a particular participant be performed by the same TI, and effectiveness 
assessments (ATHS and GAIS) be performed by the same EI. If it is not possible to use the same 
evaluator to follow the participant, it is recommended that evaluations overlap (examine the 
participant together and discuss findings) for at least 1 visit.
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8.1.4.
Other Effectiveness Measures
Other effectiveness measures include:

Treatment satisfaction questions:
o
Participant satisfaction with treatment on a 5-point scale ranging from 1 (very
dissatisfied) to 5 (very satisfied) 
o
Participant satisfaction with how natural the effects of the treatment feel on a 
5-point scale ranging from 1 (very dissatisfied) to 5 (very satisfied) and 
participant satisfaction with how natural the effects of the treatment look on a 
5-point scale ranging from 1 (very dissatisfied) to 5 (very satisfied) 
o
Participant response on the treatment meeting expectation (yes/no)
o
Participant response on interest to continue to use the treatment (yes/no)
o
Participant response on willingness to recommend treatment to a friend (yes/no)

Participant response to the participant’s self-perception of age question to provide
feedback on how old or young (in years) he/she looks based on facial appearance 

Volume change of each temple from baseline as assessed by 3D imaging
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Assessment
Timing
Measurement
Satisfaction with 
treatment
Treatment group: all on-site 
visits after last treatment
Control group: all on-site visits 
after optional last treatment
Direct question. Participants respond to item as:
5  Very satisfied
4  Satisfied
3  No opinion
2  Dissatisfied
1  Very dissatisfied
Natural look and 
feel of the results
Treatment group: all on-site 
visits after last treatment
Control group: all on-site visits 
after optional last treatment
Two direct questions, one on natural look and one on 
natural feel. Participants respond to each item as:
5  Very satisfied
4  Satisfied
3  No opinion
2  Dissatisfied
1  Very dissatisfied
Treatment meeting 
expectation
Treatment group: all on-site 
visits after last treatment
Control group: all on-site visits 
after optional last treatment
Direct question. Participants’ possible answers are:
Yes
No
Likelihood of 
continuing 
treatment
Treatment group: all on-site 
visits after last treatment
Control group: all on-site visits 
after optional last treatment
Direct question. Participants’ possible answers are:
Yes
No
Willingness to 
recommend 
treatment
Treatment group: all on-site 
visits after last treatment
Control group: all on-site visits 
after optional last treatment
Direct question. Participants’ possible answers are:
Yes
No
Participant’s self-
perception of age
Treatment group: randomization 
and all on-site visits after last 
treatment
Control group: randomization 
and all on-site visits after 
optional last treatment
Direct question. Participants are asked to provide 
feedback on how, in the past week, they have 
perceived their facial appearance makes them look. 
Temple volume
All on-site visits starting from 
randomization visit for both 
groups
Change in temple volume calculated by image analysis 
technician from baseline and follow-up 3D images
There are no pandemic or natural disaster-related protocol modifications for the 3D facial
imaging. If a site visit is missed at which this assessment was planned, the assessment may be 
performed as an unscheduled or follow-up visit.
If travel restrictions or other changes in local regulations in light of a pandemic or natural 
disaster prevent the participant from in-clinic visits, some study assessments may be conducted 
remotely. For Patient Reported Outcome assessments, the site or designee may provide the 
questionnaires to the participant for completion.
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8.2.
Safety Assessments
Safety measures include:

Participant assessment of procedural pain after study injection on an 11-point scale 
ranging from 0 (no pain) to 10 (worst pain imaginable)

The presence and severity of ISRs, which will be recorded in the participant’s safety diary.
Safety diaries will be recorded daily for 30 days starting on the day of treatment. 

AEs from TI observation and inquiry at scheduled follow-up visits

Participant’s assessment of jaw function on the Jaw Functional Limitation Scale.
Assessment on Day 14 after each treatment will be recorded along with safety diaries, 
while for other visits it will be performed on-site.

Monitoring of concomitant medications and concurrent procedures
The participant’s safety diary will list the following ISRs that have been reported previously with 
HA dermal filler injections:

Redness

Pain after injection

Tenderness to touch

Firmness

Swelling

Lumps/bumps

Bruising

Itching

Discoloration
Participants are to bring the safety diaries to the visits 1 month after each treatment for review by 
the TI, and the TI will determine if the ISR qualifies as an AE. The ongoing ISRs will be 
reported on the ISR eCRF.
AEs will be monitored continuously throughout the study and documented on the AE eCRF.
Vital sign measurements, including blood pressure (systolic and diastolic, while participant is 
seated), temperature, pulse, and respiratory rate will also be performed. 
There are no pandemic or natural disaster-related protocol modifications for physical 
examinations or blood draws for laboratory testing. If a site visit is missed at which physical 
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examinations or laboratory testing was planned, this assessment may be performed as an 
unscheduled or follow-up visit.
If travel restrictions or other changes in local regulations in light of a pandemic or natural 
disaster prevent the participant from in-clinic visits, participant visits may be conducted via 
phone, video conference, or remotely.
8.2.1.
Clinical Safety Laboratory Assessments
Hematology and blood chemistry tests will be performed as described in Appendix 10.2.
At screening, the TI will assess the clinical significance of any values outside the reference 
ranges provided by the laboratory, and participants with abnormalities judged to be clinically 
significant will be excluded from the study.
The TI must review the laboratory report and document this review and record any clinically
relevant changes occurring during the study in the AE section of the eCRF. The laboratory 
reports must be filed with the source documents. Clinically significant abnormal laboratory
findings are those that are not associated with the underlying disease, unless judged by the TI to 
be more severe than expected for the participant’s condition.
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study are to be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator.

If such values do not return to normal/baseline within a period of time judged reasonable 
by the investigator, the etiology is to be identified and the sponsor notified.

All protocol-required laboratory assessments, as defined in Appendix 10.2, must be 
conducted in accordance with the SoA (Section 1.3).

If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded as an SAE or AE in the eCRF.

Urine or blood pregnancy tests will be used at the study site at screening, before each 
study treatment, and at study exit for female participants of childbearing potential.

If a participant who underwent at least 1 treatment withdraws from the study before the 
Month 6 visit, he/she must be followed up for hematology test, clinical chemistry, and 
routine urinalysis at study exit for safety.
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8.3.
Adverse Events and Serious Adverse Events
AEs will be monitored throughout the study beginning with signing of the ICF. At each 
postbaseline visit, the TI will begin querying for AEs by asking each participant a general, 
nondirected question such as “Have you had any changes to your condition since your last visit?” 
Previous AEs and changes in therapy/concomitant medications are to be updated. Directed 
questioning and examination will then be done as appropriate. All reportable AEs and clinically
significant abnormal laboratory findings will be documented on the appropriate eCRF.
The definitions of an AE/ADE or SAE/SADE and their severity can be found in Appendix 10.7.
AEs/ADEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant’s legally authorized representative).
The PI/TI and any qualified designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE/ADE or SAE/SADE and remain responsible for 
following up AEs/ADEs that are serious, considered related to the study intervention or study 
procedures, or that caused the participant to discontinue the study (see Section 7).
Pandemic infections should be captured as AEs. If the event meets the criteria for an SAE, then 
follow the SAE reporting directions per the protocol.
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
All SAEs/SADEs from the signing of the ICF until the last follow-up visit will be collected at the 
timepoints specified in the SoA (Section 1.3), and as observed or reported spontaneously by
study participants.
All AEs/ADEs from the signing of the ICF until the last follow-up visit will be collected at the 
timepoints specified in the SoA (Section 1.3), and as observed or reported spontaneously by
study participants.
Medical occurrences that begin before the start of study intervention, but after obtaining 
informed consent will be recorded in the AE section of the eCRF and will be considered 
pretreatment AEs.
All SAEs/SADEs will be recorded and reported to the sponsor or designee within 24 hours, as 
indicated in Appendix 10.7. The PI/TI will submit any updated SAE data to the sponsor within 
24 hours of it being available.
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PIs/TIs are not obligated to actively seek AE/ADE or SAE/SADE information after conclusion 
of the study participation. However, if the PI/TI learns of any SAE/SADE, including a death, at 
any time after a participant has been discharged from the study, and he/she considers the event to 
be reasonably related to the study intervention or study participation, the PI/TI must promptly 
notify the sponsor.
8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs/ADEs and SAEs/SADEs 
and the procedures for completing and transmitting SAE/SADE reports are provided in 
Appendix 10.7.
Care will be taken not to introduce bias when detecting AEs/ADEs and/or SAEs/SADEs. 
Open-ended and nonleading verbal questioning of the participant is the preferred method to 
inquire about AE/ADE/SAE/SADE occurrences.
8.3.3.
Follow-up of AEs and SAEs
After the initial AE/ADE/SAE/SADE report, the TI is required to proactively follow each 
participant at subsequent visits/contacts. All AEs/ADEs/SAEs/SADEs will be followed until 
resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up 
(as defined in Section 7.3).
The PI/TI is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor medical safety 
physician to elucidate the nature and/or causality of the AE/ADE or SAE/SADE as fully as 
possible. This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals.
If a participant dies during participation in the study or during a recognized follow-up period, the 
PI/TI will provide the sponsor medical safety physician with a copy of any postmortem findings 
including histopathology.
New or updated information will be recorded in the originally completed eCRF.
The PI/TI will submit any updated SAE/SADE data to the sponsor within 24 hours of receipt of 
the information.
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8.3.4.
Regulatory Reporting Requirements for SAEs

Prompt notification by the PI/TI to the sponsor of an SAE/SADE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met. 

The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IECs, and investigators. 

A PI who receives an investigator safety report describing an SAE/SADE or other specific 
safety information (eg, summary or listing of SAEs/SADEs) from the sponsor will review 
and then file it along with the IB and will notify the IEC, if appropriate according to local 
requirements.
8.3.5.
Pregnancy

Details of all pregnancies in female participants will be collected after the start of study 
intervention and until the last follow-up visit.

If a pregnancy is reported, the PI/TI is to inform the sponsor within 24 hours of learning 
of the pregnancy.

The PI/TI shall (1) instruct the participant to notify her physician of the presence of the 
investigational device and (2) follow the pregnancy to term or termination. Best practices 
are to be followed in order to ensure the welfare of the participant and the fetus. The 
sponsor medical safety physician will contact the PI/TI to obtain information about the 
pregnancy outcome. The participant will continue to be followed, and the pregnancy will 
be documented as a protocol deviation.

The pregnancy outcome of a spontaneous or elective abortion, stillbirth or congenital 
anomaly is considered a SAE and must be reported to AbbVie within 24 hours after the 
site becomes aware of the event.
8.3.6.
Medical Device Deficiencies
Medical devices are being provided for use in this study as the study intervention. In order to 
fulfill regulatory reporting obligations worldwide, the PI/TI is responsible for the detection and 
documentation of events meeting the definition of device deficiency that occur during the study
with such devices.
The definition of a medical device deficiency can be found in Appendix 10.7.
NOTE: Device deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.3 and Appendix 10.7 of the protocol.
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8.3.6.1.
Time Period for Detecting Medical Device Deficiencies

Medical device events or malfunctions of the device that result in an incident will be 
detected, documented, and reported during all periods of the study in which the medical 
device is used.

If the PI/TI learns of any device deficiency at any time after a participant has been 
discharged from the study, and such an event is considered reasonably related to a medical 
device provided for the study, the PI/TI will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 10.7. 
8.3.6.2.
Follow-up of Medical Device Deficiencies

Follow-up applies to all participants, including those who discontinue study intervention
or the study.

The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.

The device deficiency will be reported to the sponsor by email. If email is unavailable, 
then fax will be used.

The same individual will be the contact for the receipt of device deficiency reports and 
SAEs.
8.3.6.3.
Prompt Reporting of Device Deficiencies to Sponsor

Device deficiencies that are potentially related to SAEs will be reported to the sponsor 
within 24 hours after the PI/TI determines that the event meets the protocol definition of a 
medical device deficiency.

The medical device deficiency will be reported to the sponsor by email. If email is 
unavailable, then fax will be used.

The sponsor will be the contact for the receipt of device deficiency reports.
8.3.6.4.
Regulatory Reporting Requirements for Device Deficiencies

The PI/TI will promptly report all device deficiencies occurring with any medical device 
provided for use in the study in order for the sponsor to fulfill the legal responsibility to 
notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.

The PI, or responsible person according to local requirements (eg, the head of the medical 
institution), will comply with the applicable local regulatory requirements relating to the 
reporting of device deficiencies to the IEC.
8.4.
Treatment of Overdose
Overdose is not applicable for this study.
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8.5.
Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study. 
8.6.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7.
Genetics
Genetics are not evaluated in this study.
8.8.
Biomarkers
Biomarkers are not evaluated in this study.
8.9.
Immunogenicity Assessments
Immunogenicity is not evaluated in this study.
8.10.
Health Economics
Health economics parameters are not evaluated in this study.
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9.
Statistical Considerations
A separate SAP will be prepared to provide specifications for all analyses. The plan will be 
finalized and approved prior to clinical database lock. The database will be locked and analyzed 
at the end of study (all data collected through the end of the study).
In general, descriptive statistics will be presented. Categorical variables will be summarized with 
response frequencies and percentages. Continuous variables will be summarized by descriptive 
statistics for the number of participants, mean, median, standard deviation, Q1, Q3, minimum, 
and maximum. Where appropriate, 2-sided 95% CIs for mean or proportion will be provided as 
part of the summary.
Every attempt will be made to collect complete data and limit the occurrence of missing data. No 
imputation of missing data is planned, except for the primary effectiveness analyses as described 
in Section 9.4.2.2. Deviations from the analyses planned in the SAP will be documented in the 
clinical study report.
Statistical analysis activities will be conducted by the Coordinating Investigator or by a third 
party delegated by the Coordinating Investigator.
9.1.
Statistical Hypotheses
The null and alternative hypotheses are:
Ηo:  Pv = Pc
Ηa:  Pv ≠ Pc
where Pv and Pc denote the responder rates for the treatment group at Month 6 after last 
control-period treatment, and control group at Month 6 after randomization, respectively 
(responder is defined as a participant with at least 1-grade improvement on the ATHS in both 
temples based on the EI’s live assessment of temple hollowing). The null hypothesis for 
effectiveness is that the responder rate at Month 6 is the same for the treatment and control 
groups. The alternative hypothesis is that the ATHS responder rate for the treatment group is 
different from the control group at Month 6.
9.2.
Sample Size Determination
The primary effectiveness measure is the change from baseline on the 5-point ATHS at Month 6. 
The change can range from -4 to +2. The primary effectiveness variable is the ATHS responder 
status, which is determined by an improvement of 1 grade or more (ie, a change score of -4 to -1) 
in both temples. 
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Under a 2:1 randomization ratio, a total of 90 participants in the treatment group and 
45 participants in the control group at the primary timepoint will provide at least 90% power to 
detect a difference of 30% in the responder rates between the groups. This calculation is based 
on a 2-sided Fisher’s exact test at the 5% level, using responder rates of 65% and 35% for both 
temples simultaneously for participants in the treatment and control groups, respectively. The 
assumption of a 65% treatment responder rate is a conservative estimate based on the observed 
responder rate in previous filler studies for other facial areas. Also, while a 30% difference from 
control is greater than a minimally important difference, a 35% responder rate is a reasonable 
upper limit of expectation for the control group, based on validation results of the ATHS and 
control group responder rates observed in previous filler studies. Furthermore, assuming a 
dropout rate of 20% after randomization through the Month 6 visit, 168 randomized participants 
are needed, with 112 participants in the treatment group and 56 participants in the control group 
(2:1 ratio).
If the underlying true responder rate is 65%, 90 participants in the treatment group results in a 
binomial likelihood of 86.5% to observe a responder rate of at least 60%. 
With up to 9 investigational sites planned, it is recommended that no site randomize more than 
twice the proportional share of 1 more site = 2 × [168/(n+1)]. The recommended minimum is 
8 participants per site, which will guarantee that each treatment group has at least 2 participants 
at each site (allowing for mixed randomization blocks of 3 and 6 that incorporate the 
2:1 randomization ratio). 
The commercial software PASS (2008, Version 8.0.13) was used for the power calculation. The 
sample size calculation used an inequality test for 2 proportions to demonstrate that the treatment 
group is superior to the control group.
Due to local guidelines to prevent and mitigate the effects of a pandemic or natural disaster, it is 
understood that some participants may not be able to complete all site visits as indicated per 
protocol. If more than 20% of the randomized participants fail to complete the primary
timepoint ATHS assessment in-clinic, additional participants will be enrolled.
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9.3.
Populations for Analyses
The following populations are defined:
Population
Description
mITT
All randomized participants who have nonmissing baseline ATHS. This population will be used as 
the full analysis set.
PP
All participants in the mITT population with nonmissing primary effectiveness endpoint 
(ie, nonmissing ATHS for Month 6 for each temple) and with no significant protocol deviations 
that could affect the primary effectiveness endpoint. A significant deviation that occurs after the 
primary endpoint would not lead to exclusion from the PP analysis.
Safety
All randomized participants who have at least 1 study treatment intervention (ie, VOLUMA with 
Lidocaine or no treatment).
Analyses of safety variables will be performed on the safety population, with participants 
grouped as treated. Unless specified otherwise, all other analyses will be performed on the mITT 
population, with participants grouped as randomized. The PP population will be used to perform 
PP sensitivity analysis, with participants grouped as randomized, for the primary endpoint.
9.4.
Statistical Analyses
The SAP will be finalized before database lock and will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the most important endpoints, including primary and secondary
endpoints.
9.4.1.
General Considerations
The effectiveness analyses will be based on the mITT population in general, and PP sensitivity
analysis of the primary endpoint will be based on the PP population. Baseline for effectiveness is 
defined as the last nonmissing effectiveness assessment before randomization. 
All statistical tests will be 2-sided hypothesis tests performed at the 5% level of significance for 
main effects. A gatekeeping procedure will be used for hypothesis testing of the primary 
endpoint (ATHS responder) and 2 of the secondary endpoints (responder rates for EI and 
participant assessments of GAIS) following a predefined sequence to control the overall type I 
error rate at the 0.05 level. The primary hypothesis must be rejected in order to test the responder 
rate for EI assessment of GAIS. Additionally, statistical significance must be established for the 
responder rate for EI assessment of GAIS in order to assess the hypothesis for the responder rate 
for participant assessment of GAIS. 
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9.4.2.
Primary Endpoint
9.4.2.1.
Definition of Endpoint
Primary effectiveness endpoint:

Responder status based on the EI’s live assessment of temple hollowing using ATHS at 
Month 6 after last treatment for treatment group and after randomization for control 
group, where a “responder” is a participant with at least 1-grade improvement on the 
ATHS in both temples.
9.4.2.2.
Main Analytical Approach
The primary effectiveness analysis will be performed on the mITT population. The study
intervention will be determined to be clinically effective if the following criterion is met:

The ATHS responder rate for the treatment group is statistically superior to the responder 
rate for the control group at Month 6
Two-sided Fisher’s exact test with 5% significance level will be used to compare responder rates 
between treatment and the control group. If the 2-sided p-value is ≤0.05, which implies that the 
responder rate is different for treatment than for the control group, and the point estimate of the 
responder rate for the treatment group is greater than for the control group, then treatment will be 
considered clinically effective. In addition, responder rates and 95% CIs will be displayed within 
and between treatment and control groups.
If there are any mITT participants with missing primary effectiveness endpoint, the following 
missing-data handling method is planned for the primary analysis. 

Multiple imputation by the fully conditional specification method for ordinal data (via 
SAS procedure MI with FCS logistic statement) will be done with 5 imputed datasets for 
participants with missing primary endpoint, using the model below:

Month 6 ATHS = β0 + β1 × Baseline ATHS + β2 × Month 1 ATHS + β3 × Month 3 ATHS

Intermittent missing ATHS at Month 1 and Month 3 will be imputed by similar models 
using ATHS at previous visits as covariates. 

The imputation will be performed by treatment group and by side (left and right).

After imputation, the changes from baseline will be calculated, from which the responder 
status will be determined.

Analyses of individual imputed datasets will be performed by SAS procedure FREQ and 
then pooled by SAS procedure MIANALYZE to display combined responder rates and 
95% CIs within and between treatment and control groups and to generate an associated 
p-value for the comparison of responder rates between groups.
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9.4.2.3.
Sensitivity Analyses
Since multiple imputation will be used for the primary analysis if the observed dataset is not 
complete for the primary endpoint, a sensitivity analysis will then be done using observed data, 
without imputation of missing data. 
If so, a second sensitivity analysis will be done after imputation for missing data by baseline-
observation carried-forward (for reversion to baseline), which effectively handles participants 
with missing primary effectiveness as nonresponders.
The primary analysis using 2-sided Fisher’s exact test or multiple imputation (depending on 
whether any participants have missing primary effectiveness endpoint as mentioned in 
Section 9.4.2.2) will also be repeated on the PP population as a third sensitivity analysis.
9.4.3.
Secondary Endpoints
Secondary effectiveness endpoints:

Responder status based on the EI’s assessment of the temple area using GAIS at Month 6 
after last treatment for treatment group and after randomization for control group, where a 
“responder” is a participant with grade “improved” or “much improved” on GAIS.

Responder status based on the participant’s assessment of the temple area using GAIS at 
Month 6 after last treatment for treatment group and after randomization for control 
group, where a “responder” is a participant with grade “improved” or “much improved” 
on GAIS.

Change from baseline on FACE-Q Satisfaction with Facial Appearance questionnaire at 
Month 6 after last treatment for treatment group and after randomization for control 
group.

Change from baseline on FACE-Q Satisfaction with Temples questionnaire at Month 6 
after last treatment for treatment group and after randomization for control group.
The following analysis will be performed for the secondary effectiveness endpoints:

For the responder status based on the EI’s and participant’s assessments of GAIS at 
Month 6, the responder rates with 95% exact CI will be summarized, and p-value for 
between treatment group comparisons will be based on 2-sided Fisher’s exact test using 
observed data. 

Change from baseline on participant responses on FACE-Q Satisfaction with Facial 
Appearance and with Temples questionnaires, for the Rasch-transformed score (0-100), 
will be analyzed using a repeated measures mixed-effects model, and the p-value for the 
between treatment group comparison will be provided for Month 6.
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9.4.4.
Additional Endpoints
Other effectiveness endpoints:

Primary and secondary measures at other visits

Full-scale ATHS scores at each measurement visit

Full-scale EI assessment of GAIS at each measurement visit

Full-scale participant assessment of GAIS at each measurement visit

Percentage of participants showing improvement on the FACE-Q Satisfaction with Facial 
Appearance questionnaire, for the Rasch-transformed score, at each measurement visit

Participant responses to FACE-Q Satisfaction with Facial Appearance questionnaire, for 
the Rasch-transformed score (0-100), unadjusted for baseline, at each measurement visit

Percentage of participants who respond as Somewhat Satisfied or Very Satisfied for 
3-5 items (to be specified in the SAP) on the FACE-Q Satisfaction with Facial Appearance 
questionnaire at Month 6 

Percentage of participants showing improvement on the FACE-Q Satisfaction with 
Temples questionnaire, for the Rasch-transformed score, at each measurement visit

Participant responses to FACE-Q Satisfaction with Temples questionnaire, for the 
Rasch-transformed score (0-100), unadjusted for baseline, at each measurement visit

Percentage of participants who respond as Somewhat Satisfied or Very Satisfied for 
3-5 items (to be specified in the SAP) on the FACE-Q Satisfaction with Temples 
questionnaire at Month 6

Participant’s satisfaction with treatment questions and age perception question, at each 
measurement visit

Volume change of each temple from baseline as assessed by 3D imaging, at each 
measurement visit
The following analyses will be performed for the other effectiveness variables. There are 
5 variables underlying the primary and secondary variables:

Overall score of ATHS at each measurement visit, baseline and change from baseline, 
summarized with response frequencies and descriptive statistics for each treatment group, 
using the temple with worse baseline score to represent the participant (using the left side 
if both temples have the same baseline score).

Overall score of EI assessment of GAIS at each measurement visit, baseline and change 
from baseline, summarized with response frequencies and descriptive statistics for each 
treatment group.

Overall score of participant assessments of GAIS at each measurement visit, baseline and 
change from baseline, summarized with response frequencies and descriptive statistics for 
each treatment group.
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
Participant responses to FACE-Q Satisfaction with Facial Appearance questionnaire, for 
item-level scores for ordinal categories from 1 to 4 for each of 10 items at each 
measurement visit, baseline and change from baseline, summarized with response 
frequencies and descriptive statistics for each treatment group.

Participant responses to FACE-Q Satisfaction with Temples questionnaire, for item-level 
scores for ordinal categories from 1 to 4 for each of 12 items at each measurement visit, 
baseline and change from baseline, summarized with response frequencies and descriptive 
statistics for each treatment group.
Other analyses for additional endpoints will be detailed in the SAP.
9.4.5.
Safety Analyses
The safety analysis will be performed using the safety population and will be fully defined in the 
SAP. The safety parameters will include procedural pain, ISRs, AEs, jaw function assessment, 
vital signs, concomitant medications and procedures and clinical laboratory values.
Procedural pain will be summarized using response frequencies and descriptive statistics. ISRs 
reported by participants will be summarized at the participant level by symptom incidence, 
maximum reported severity, number of ISR days, maximum reported contiguous duration 
(maximum successive days of the ISR) and total duration days (number of days from first onset 
day to last occurrence) for initial and touch-up, separately. The summary of procedural pain and 
ISRs will be done separately for the initial treatment group and the optional treatment group. 
9.4.5.1.
Adverse Events
An AE will be considered a TEAE if the AE began or worsened (increased in severity or became 
serious) on or after the date (and time, if known) of the first study treatment for treatment group 
or of randomization for control group (participants are grouped as treated). An AE will be 
considered a TESAE if it is a TEAE that additionally meets any SAE criterion.
Overall summary of AEs will be presented for the following:

TEAEs

Treatment-related TEAEs

Treatment-related TEAEs at injection site

Treatment-related TEAEs not at injection site

TESAEs

Treatment-related TESAEs

Treatment-related TESAEs at injection site
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
Treatment-related TESAEs not at injection site

Discontinued due to TEAE

Deaths
The incidence of TEAEs and treatment-related TEAEs will be presented for the following:

by primary SOC and PT

by primary SOC, PT, and maximum severity
The incidence of treatment-related TEAEs will also be presented for the following:

by maximum severity, time to onset, duration, action taken and outcome
Summary tables will be provided for participants with TESAEs and participants with TEAEs 
leading to discontinuation if 5 or more participants reported such events. Listings of all AEs, 
SAEs, and AEs leading to discontinuation by participant will be presented.
If more than 1 AE is coded to the same PT for the same participant, the participant will be 
counted only once for that PT using the most severe and most related occurrence for the 
summarizations by severity and by relationship to study intervention. 
9.4.5.2.
Vital Signs
Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, and temperature) at 
baseline (screening) and changes from baseline at each assessment will be presented by data 
listings. No summary statistics are planned for vital signs.
9.4.6.
Other Analyses
9.4.6.1.
Study Intervention Administration Analyses
Study intervention characteristics will be summarized with descriptive statistics for anesthesia 
usage, injection volume, injection ease (11-point scale where 0 = difficult and 10 = easy) and 
product moldability (11-point scale where 0 = stiff and 10 = moldable). Injection technique and 
planes of injection will be summarized using frequency and percentages.
9.4.6.2.
Subgroup Analyses
No subgroup analysis is planned for this study.
9.5.
Interim Analyses
No interim analysis is planned for this study.
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9.6.
Data Monitoring Committee
No data monitoring committee is planned for this study.
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10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with the following:
o
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines
o
Applicable ICH/ISO GCP guidelines
o
Applicable laws and regulations, including NMPA order No. 25 (China Medical 
Device GCP)

The protocol, protocol amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IEC by the PI and the study site’s device trial 
management department and reviewed and approved by the IEC before the study is 
initiated.

Any amendments to the protocol will require IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.

The PI will be responsible for the following:

Providing written summaries of the status of the study to the IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IEC
o
Notifying the IEC of SAEs or other significant safety findings as required by IEC 
procedures
o
Providing oversight of the overall conduct of the study at the site and adherence to 
requirements of applicable local regulations, for example ICH guidelines and the IEC

During the course of the study, should it ever become necessary to remain home or to 
shelter-in-place per local, regional, or state orders, the sponsor will engage with study site 
staff in efforts to ensure the safety of participants, maintain protocol compliance, and 
minimize risks to the integrity of the study while trying to best manage participant 
continuity of care. This may include alternative methods for assessments (eg, phone 
contacts or virtual site visits) or alternative locations for safety data collection in 
agreement with the sponsor. In all cases, these alternative measures must be allowed by
local regulations and permitted by IEC. Investigators should notify the sponsor if any
urgent safety measures are taken to protect the participants against any immediate hazard.
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10.1.2.
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities as needed. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
10.1.3.
Informed Consent Process

The PI or his/her representative will explain the nature of the study to the participant or 
his/her legally authorized representative and answer all questions regarding the study.

Participants must be informed that their participation is voluntary. Participants or their
legally authorized representative will be required to sign a statement of informed consent 
that meets the requirements of local regulations, ICH guidelines, and the IEC or study site.

The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study.

A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative.

In the event of a pandemic or natural disaster, it is possible that additional protocol 
modifications not outlined in this protocol may become necessary. If this situation arises, 
in addition to the study informed consent, additional verbal consent may be obtained prior 
to these adaptations or substantial changes in study conduct in accordance with local 
regulations. Any verbal consent must be dated and documented in the source document.
10.1.4.
Data Protection

Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; any identifiable 
participant information (including facial images) will only be transferred in accordance 
with the signed Informed Consent provisions.

The participant must be informed that his/her personal study-related data will be used by
the sponsor in accordance with local data protection laws. The level of disclosure must 
also be explained to the participants who will be required to give consent for their 
personal data to be used as described in the informed consent.

The participant must be informed that his/her medical records may be examined by
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IEC members, and by inspectors from regulatory authorities.
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
Management of privacy incidents relating to clinical trial participant personal data, as well 
as handling of data participant rights requests (if applicable), should be handled in 
accordance with the agreed upon clinical trial agreement provisions.
10.1.5.
Dissemination of Clinical Study Data

Study data and information may be published in nonpromotional, peer-reviewed 
publications either by or on behalf of the sponsor.

Clinical study reports, safety updates, and annual reports will be provided to regulatory
authorities as required.

Study data will be posted on www.clinicaltrials.gov as required.
10.1.6.
Data Quality Assurance

All participant data relating to the study will be recorded on printed or eCRFs unless 
transmitted to the sponsor or designee electronically (eg, 3D imaging data). The PI is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the eCRF.

The PI must maintain accurate documentation (source data) that supports the information 
entered in the eCRF.

The PI must permit study-related monitoring, audits, IEC review, and regulatory agency
inspections and provide direct access to source data documents.

Monitoring details describing strategy (eg, risk-based initiatives in operations and quality
such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in the Monitoring Plan.

The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.

The sponsor assumes accountability for actions delegated to other individuals (eg, contract 
research organizations).

Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements.

Records and documents, including signed ICFs, pertaining to the conduct of this study
must be retained by the PI for 2 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed 
during the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor.
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
Data management activities will be conducted by the Coordinating Investigator or by a 
third party delegated by the Coordinating Investigator.

In the event of a pandemic or natural disaster, remote monitoring of data may be 
employed if allowed by the local regulatory authority, IEC, and the study site.
10.1.7.
Source Documents

Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the PI’s site.

Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents, or the discrepancies must be explained. The PI may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available.

Definition of what constitutes source data can be found in Section 1.51 of ICH E6, Good 
Clinical Practice: Consolidated Guidance and must follow ALCOA (ie, records must be 
attributable, legible, contemporaneous, original, and accurate).
10.1.8.
Study and Site Start and Closure
The sponsor or designee reserves the right to close the study site or terminate the study at any
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The PI may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or PI may include but are not limited 
to:

Failure of the PI to comply with the protocol, the requirements of the IEC or local health 
authorities, the sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the PI

Discontinuation of further study intervention development
Per ISO 14155, if a study is prematurely terminated or suspended due to safety issues, the 
sponsor shall inform all investigators and the regulatory authorities of the termination or 
suspension and the reason(s) for the termination or suspension. The IEC is also to be informed 
promptly and provided the reason(s) for the termination or suspension by the sponsor or by the 
PI, as specified by the applicable regulatory requirements. If a premature termination or 
suspension occurs, the sponsor shall remain responsible for providing resources to fulfill the 
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protocol obligations and existing agreements for follow-up of participants enrolled in the study, 
and each PI or authorized designee shall promptly inform enrolled participants, if applicable.
10.1.9.
Publication Policy

Allergan as the sponsor has proprietary interest in this study. Authorship and manuscript 
composition will reflect joint cooperation between multiple investigators and sites and 
Allergan personnel. Authorship will be established prior to the writing of the manuscript. 
As this study involves multiple centers, no individual publications will be allowed prior to 
completion of the final report of the multicenter study except as agreed with the sponsor.

The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data.

Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.
10.1.10.
Compliance with Protocol
The PI is responsible for compliance with the protocol at the investigational site. 
A representative of the sponsor will make frequent contact with the PI and his/her research staff 
and will conduct regular monitoring visits at the site to review participant and study intervention 
accountability records for compliance with the protocol. Protocol deviations will be discussed 
with the PI upon identification. The use of the data collected for the participant will be discussed 
to determine if the data are to be included in the analysis. The PI will enter data that may be 
excluded from analysis as defined by the protocol deviation specifications. Significant protocol 
deviations (including those that may be due to a pandemic or natural disaster) will be reported to 
the IEC according to the IEC’s reporting requirements. Participants will be asked questions to 
evaluate compliance with safety diaries.
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10.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 10-1 will be performed by the local laboratory.

Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol.

Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations.
Table 10-1
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet count
Red blood cell indices:
Mean corpuscular volume
Mean corpuscular hemoglobin
Mean corpuscular hemoglobin 
concentration
% Reticulocytes
White blood cell count with 
differential (absolute):
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Red blood cell count
Hemoglobin
Hematocrit
Clinical 
Chemistry
Urea Nitrogen/urea  
Potassium
Aspartate Amino 
Transferase 
Total, direct 
bilirubin
Creatinine
Sodium
Alanine amino 
Transferase 
Total protein
Glucose, fasting
Calcium
Alkaline 
phosphatase
Cholesterol, 
chloride, albumin
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood, ketones, bilirubin, urobilinogen/bilinogen, nitrite, leukocyte 
esterase/leukocyte neutrophil esterase/leukocyte

Microscopic examination (if blood or protein is abnormal)
Other 
Screening 
Tests

Human chorionic gonadotropin pregnancy test at screening and test on admission days as 
needed for women of childbearing potential
Investigators must document their review of each laboratory safety report.
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10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
Not applicable. See Appendix 10.7.
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10.4.
Appendix 4: Abbreviations
Abbreviation
Definition
3D
3-dimensional
ADE
adverse device effect
AE
adverse event
ATHS
Allergan Temple Hollowing Scale
BDDE
1,4-butanediol diglycidyl ether
CDISC
Clinical Data Interchange Standards Consortium
CE
Conformité Européene
CI
confidence interval
eCRF
electronic case report form
EI
Evaluating Investigator
FDA
United States Food and Drug Administration
GAIS
Global Aesthetic Improvement Scale
GCP
Good Clinical Practice
HA
hyaluronic acid
HIV
human immunodeficiency virus
IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IDFU
investigational directions for use
IEC
independent ethics committee
ISO
International Organization for Standardization
ISR
injection site response
IWRS
interactive web response system
mITT
modified intent-to-treat
NCI
National Cancer Institute
NCT
national clinical trial number on www.clinicaltrials.gov
NMPA
National Medical Products Administration
PI
Principal Investigator
PP
per-protocol
PT
preferred term
SADE
serious adverse device effect
SAE
serious adverse event
SAP
statistical analysis plan
SoA
schedule of activities
SOC
system organ class
TEAE
treatment-emergent adverse event
TESAE
treatment-emergent serious adverse event
TI
Treating Investigator
USADE
unanticipated serious adverse device effect
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10.5.
Appendix 5: Standard Discontinuation Criteria
This table provides participant discontinuation criteria for this protocol. CDISC terminology is 
used, and thus subject or patient is used instead of participant (as used elsewhere in this 
protocol). These terms are interchangeable.
CDISC Submission Value
CDISC Definition
Adverse event
Any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not 
related to the medicinal (investigational) product. For further information, see the 
ICH Guideline for Clinical Safety Data Management: Definitions and Standards 
for Expedited Reporting (modified from ICH E2A) Synonyms: side effect, adverse 
experience. See also serious adverse event, serious adverse experience. (CDISC 
glossary)
Death
The absence of life or state of being dead (NCI)
Lost to follow-up
The loss or lack of continuation of a subject to follow-up
Other
Different than the one(s) previously specified or mentioned (NCI)
Physician decision
A position, opinion or judgment reached after consideration by a physician with 
reference to subject (NCI)
Protocol deviation
An event or decision that stands in contrast to the guidelines set out by the 
protocol (NCI)
Site terminated by sponsor
An indication that a clinical study was stopped at a particular site by its sponsor 
(NCI)
Study terminated by 
sponsor
An indication that a clinical study was stopped by its sponsor (NCI)
Withdrawal by subject
An indication that a study participant has removed itself from the study (NCI)
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10.6.
Appendix 6: Study Tabular Summary
This table is intended for use in posting study information to registries (eg, ClinicalTrials.gov).
Parameter Group
Parameter
Value
Trial information
Trial Title
A multicenter, evaluator-blinded, randomized, 
no-treatment controlled study to evaluate the 
safety and effectiveness of JUVÉDERM®
VOLUMA® with Lidocaine for correction of 
temple hollowing in Chinese population
Clinical Study Sponsor
Allergan
Trial Phase Classification
N/A
Trial Indication
Temple hollowing
Trial Indication Type
Treatment
Trial Type
Effectiveness
Safety
Trial Length
14 months
Planned Country of Investigational 
Sites
China
Planned Number of Subjects
168
FDA-Regulated Device Study
No
FDA-Regulated Drug Study
No
Pediatric Study
No
Subject 
information
Diagnosis Group
Temple hollowing
Healthy Subject Indicator
No
Planned Minimum Age of Subjects
18
Planned Maximum Age of Subjects
None
Sex of Participants
Both
Stable Disease Minimum Duration
N/A
Treatments
Investigational Therapy or Treatment
JUVÉDERM® VOLUMA® with Lidocaine
Intervention Type
Device
Pharmacological Class of Invest. 
Therapy
N/A
Intervention per Administration
Up to 3 mL/temple (initial and touch-up 
combined); any single treatment: up to 
2 mL/temple
Intervention Units
mL
Dosing Frequency
Initial and touch-up treatments
Route of Administration
Injection
Current Therapy or Treatment
N/A
Added on to Existing Treatments
No
Control Type
No-treatment control
Comparative Treatment Name
None
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Parameter Group
Parameter
Value
Trial design
Study Type
Interventional
Intervention Model
Parallel
Planned Number of Arms
2
Trial is Randomized
Yes
Randomization Quotient
2:1
Trial Blinding Schema
Single-blind
Stratification Factor
None
Adaptive Design
No
Study Stop Rules
No
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10.8.
Appendix 8: Protocol Amendment History
The protocol amendment summary of changes table for the current amendment is located 
directly before the table of contents.
Amendment 2 (December 2020)
Overall Rationale for the Amendment:
The primary purpose of this protocol amendment is to update the safety laboratory assessments 
in alignment with the investigative sites’ capabilities.
Section No. and Name
Description of Change
Brief Rationale
8.2 (Safety Assessments)
Removed the term Other as an injection site 
response listed in the participant’s safety 
diary
Correction
8.2.1 (Clinical Safety 
Laboratory Assessments)
Revised the term laboratory manual to 
laboratory requirements
Correction
10.2 (Appendix 2)/Clinical 
Laboratory Tests/Table 10-1
For clinical chemistry assessments, removed 
the parameter indirect bilirubin, revised 
assessment of glucose from nonfasting to 
fasting glucose, and revised the parameter of 
blood urea nitrogen to urea nitrogen/urea
Correction
10.2 (Appendix 2)/Clinical 
Laboratory Tests/Table 10-1
For routine urinalysis, added the parameter 
bilinogen and revised the parameter 
leukocyte esterase by dipstick to leukocyte 
esterase/leukocyte neutrophil 
esterase/leukocyte
Correction
Amendment 1 (August 2020)
Overall Rationale for the Amendment:
The primary purpose of this protocol amendment was to update the needle size to include a 
25 G 1” needle and update study processes as summarized below.
Section No. and Name
Description of Change
Brief Rationale
1.1/Synopsis
Added the option of using a 25 G 1” needle
Update
1.2/Schema
Added ‘after randomization’ after ‘Optional 
treatment at Month 6’ for the control group
Improve clarity
1.3/Schedule of Activities
Added that pregnancy test is to be 
administered prior to randomization (for 
participants in the control group)
Improve clarity
Table 1-3
Added ‘After Randomization’ in the column 
‘Month 1 (+1w), Month 3 (±2w), 
Month 6 (±2w)’ for the control group
Improve clarity
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Section No. and Name
Description of Change
Brief Rationale
Table 1-3
Added a pregnancy test at study exit and 
updated corresponding language in footnotes 
for the control group
Update
Table 1-3
Removed 3D imaging and vital sign 
assessments from the optional initial 
treatment visit due to duplication with that at 
Month 6 after randomization/study exit
Improve clarity
Table 1-3
Updated language in footnote h) to clarify 
the specific visit at which laboratory testing 
is to be conducted
Improve clarity
4.3/Justification for Dose
Added the option of using a 25 G 1” needle
Update
Table 6-1
Added the option of using 25 G 1” needles 
and clarified that they will be provided 
separately. 
Update
6.1.2/Instructions for Use and 
Administration
Added the option of using a 25 G 1” needle
Update
8.1.1/Intervention 
Administration Assessments
Added that injection technique will be 
included in the evaluation of the study 
intervention
Update
8.1.1/Intervention 
Administration Assessments
Added the option of using a 25 G 1” needle
Update
8.2/Safety Assessments
Added description of how ISRs will be 
monitored
Update
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11.
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