Evaluation of Effectiveness and Safety of Belotero Balance® (+) Lidocaine for Volume Augmentation of the Infraorbital Hollow
Phase: NA
Conditions: Volume Loss in the Infraorbital Hollow Area
Sponsor: Merz North America, Inc.



Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
M930121002 
Version 5.0, 04-NOV-2021 
CONFIDENTIAL AND PROPRIETARY 
Page 2 of 111 
Changes to Previous Versions of this Report 
Version and Date 
Change 
Version 5.0, 04-
NOV-2021 
An incorrect instruction in footnote 6 in the schedule of events for the 
control/delayed-treatment subjects was included in previous versions of 
this protocol. The footnote incorrectly stated that IOH photos should only 
be taken at Visit C1-a (8 weeks after screening), if the screening photos 
were deemed unsatisfactory. In fact, all subjects in the control/delayed-
treatment group should have IOH photos taken at Screening and Visit C1-
a, as outlined in other sections of the protocol. The issue was noted after all 
control/delayed-treatment subjects had completed the affected Visit C1-a 
and for the majority of control/delayed-treatment subjects, no photo had 
been taken at Visit C1-a. The following changes to the planned IPR 
assessments, and statistical analyses were therefore included in this 
protocol amendment: 
•
Updated timepoints of photos used for IPR assessment in Section
7.2.1.3 Other Effectiveness Endpoints and Section 11.2.1.1 Merz
Infraorbital Hollow Assessment Scale (MIHAS). For subjects in
the control/delayed treatment group, photos from Screening, 8
weeks post-screening and 8 weeks post last injection will be
included in the IPR assessment.
•
Adapted the analyses of IPR assessment data to the change in
timepoints of photos used in the assessment. For subjects in the
control/delayed-treatment group, summaries will be provided for
8 weeks after screening and 8 weeks post-last injection, using the
screening photo as reference.
•
Reference to pre-treatment photos taken at the delayed treatment
baseline were removed from the definition and analysis
descriptions for the GAIS endpoints.
In Section 11.1 Visit Schedule, the definition of the primary endpoint 
visit, which is 8 weeks post screening for the control/delayed treatment 
subjects, was corrected. 
Minor formatting errors and wording changes were implemented. 
Version 4.0, 27-
JAN-2021 
•
Updated safety email address and removal of fax number (Section
12.2.2)
•
Increased the maximum enrollment per site from 24 to 26 (Sections
8.1, 9.1, 13.1)
•
Updated internal functional contributors (Section 16.5)
Version 3.0, 20-
JUL-2020 
In order to address the agency’s (FDA) concerns regarding changes in 
visual function assessments that may occur immediately after treatment, 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 of 1 1 1  
t he  prot oc ol  has  bee n  m o difie d  t o  e ns ure  t hat  s u bjects  wit h  detecte d  
a b n or malities  o n  vis ual -f u ncti o n  assess me nts  p ost-treat me nt  will  be  
referre d t o a n o p ht hal m ol o gist f or e val uati o n. T he f oll o wi n g la n g ua ge has 
bee n a d de d t o Secti o n 1 1. 2. 2. 2. 1 of t he pr ot oc ol.  
A n a b n or malit y is defi ne d as a n y para meter t hat is cli nicall y si g nifica nt i n 
nat ure or a dr o p -i n visi o n b y o ne li ne or m ore. If a n y s uc h a b n or malit y is 
detecte d o n t he vis ual -f u ncti o n assess me nts at a treat me nt visit (i nitial 
i njecti o n,  t o uc h-u p,  retreat me nt),  t he  s u bject  will  be  referre d  t o  a n  
o p ht hal m ol o gist f or f urt her e val uati o n. I n a d diti o n, t he a b n or malit y will be 
d oc u me nte d as a n A E.  
Versi o n 2. 0, 1 4 -
J U L- 2 0 2 0 
•
A n a b n or malit y i n vis ual ac uit y usi n g t he S nelle n c hart was pre vi o usl y
defi ne d as a dr o p -i n visi o n b y t w o li nes or m ore. T he a ge nc y ( F D A)
i n dicate d t hat t he S nelle n c hart lac ks u nif or mit y a n d t h us t he defi niti o n
of a b n or mal vis ual assess me nt as a dr o p b y 2  li nes or m ore is i n here ntl y
fla we d. T o a d dress t his c o ncer n, t he pr ot oc ol was re vise d t o i ncl u de a n
e val uati o n f or a n y s u bject w h o e x perie nces a w orse ni n g of t heir vis ual
ac uit y (i.e., dr o p-i n visi o n b y o ne li ne or m ore o n t he S nelle n c hart).
•
Pre vi o usl y, pre -treat me nt visi o n assess me nts were t o be perf or me d at
t he scree ni n g visit a n d n ot t he first treat me nt visit pri or t o i njecti o n. I n
or der t o a d dress t he F D A’s c o ncer ns re gar di n g t he nee d t o e ns ure t hat
s u bjects are a p pr o priatel y scree ne d f or a n y visi o n c ha n ges d uri n g t he
c o urse of t he st u d y, 
 has be e n re vise d t o i n dicate t hat visi o n
assess me nts will be perf or me d at t he scree ni n g visit, as well as, t he
treat me nt visit pri or t o i njecti o n.
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Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
M930121002 
Version 5.0, 04-NOV-2021 
CONFIDENTIAL AND PROPRIETARY 
Page i of iii 
2 SYNOPSIS 
Title of Study 
Evaluation of Effectiveness and Safety of Belotero Balance® (+) Lidocaine 
for Volume Augmentation of the Infraorbital Hollow 
Study Identifier 
M930121002 
Investigators, 
Study Sites 
This study will be conducted at up to 9 study centers in the United States. 
Investigational 
Medical Device 
Belotero Balance® (+) Lidocaine (BBL) 
Indication 
Correction of volume loss in the infraorbital hollow area 
Objectives 
Effectiveness 
Confirm the effectiveness of BBL injection for the correction of volume 
loss in the infraorbital hollow (IOH) area by demonstrating superiority to 
untreated control. 
Safety 
Confirm the safety of BBL injection for the correction of volume loss in the 
IOH area. 
Effectiveness 
Evaluation 
Primary endpoint 
• 
Proportion of responders at Week 8 on the Merz Infraorbital Hollow 
Assessment Scale (MIHAS), as assessed live by a blinded evaluator. 
Note: Responder is defined as a subject with at least 1-point 
improvement from baseline on MIHAS of both IOHs. 
Note: For subjects randomized to treatment, if no touch-up is 
performed, the primary effectiveness MIHAS assessment will occur 
8 weeks post baseline injection. If a touch-up is performed, the primary 
effectiveness MIHAS assessment will be completed 8 weeks post touch-
up. For subjects randomized to control/delayed-treatment, the primary 
effectiveness assessment will occur 8 weeks from the screening visit. 
Secondary endpoints 
Note: For all secondary endpoints, Week 8 corresponds to the time from 
last injection (either baseline or touch-up injection) for subjects randomized 
to treatment only (TN and TC groups). 
• 
Global Aesthetic Improvement Scale (GAIS) score at Week 8, as 
assessed by the treating investigator. 
• 
GAIS score at Week 8, as assessed by the subject. 
• 
FACE-Q™ Satisfaction with Eyes scores and changes from baseline to 
Week 8, as assessed by the subject. 
 
Note: FACE-Q evaluates both eyes concurrently. 

Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
M930121002 
Version 5.0, 04-NOV-2021 
CONFIDENTIAL AND PROPRIETARY 
Page ii of iii 
Safety Evaluation 
Secondary endpoints 
• 
Incidence of treatment-emergent adverse events (TEAEs) related to 
BBL. 
• 
Incidence of treatment-emergent serious adverse events (TESAEs) 
related to BBL. 
Introduction, 
Study Design 
Overview, and 
Methodology 
This is a prospective, multicenter, randomized, evaluator-blinded, 
comparative, pivotal study designed to evaluate the effectiveness and safety 
of BBL for the correction of volume loss in the IOH area. 
All eligible subjects will be randomized to 4 groups using a 2:2:1:1 ratio as 
follows: BBL with needle (TN), BBL with cannula (TC), control/delayed 
treatment BBL with needle (CDTN), and control/delayed treatment BBL 
with cannula (CDTC). 
Subjects randomized to treatment will receive a BBL injection in both IOHs 
and will be assessed at Week 4 for a touch-up in one or both IOHs. 
These subjects will also be eligible for a retreatment at 48 weeks post last 
injection (i.e., baseline injection or touch-up, if applicable) and then be 
followed for an additional 24 weeks, for a total study duration of 72 weeks 
if no touch-up is performed and 76 weeks if a touch-up is performed. 
Subjects randomized to the control/delayed-treatment group will remain 
untreated for 8 weeks. After all applicable effectiveness endpoint 
assessments have been completed, the control/delayed-treatment subjects 
will receive BBL injections and will be assessed 4 weeks after their initial 
injection for a touch-up in one or both IOHs. These subjects will be 
followed for 48 weeks post last injection (i.e., baseline injection or touch-
up, if applicable) and will not be offered retreatment. 
Number of Study 
Subjects 
A total 150 subjects will be randomized. 
Main Inclusion/ 
Exclusion Criteria 
Select inclusion criteria are as follows: 
• 
Subject is a candidate for bilateral IOH treatment. 
• 
Subject has symmetrical right and left IOHs with the same MIHAS 
score of 2 or 3 (moderate or severe), as assessed live by a blinded 
evaluator. 
• 
Female or male ≥ 22 and ≤ 65 years old. 
Select exclusion criteria are as follows: 
• 
Prior lower-eyelid surgery, including orbital or midface surgery, or a 
permanent implant or graft in the midfacial region that could interfere 
with effectiveness assessments. 
• 
Previous treatment with fat injections or permanent and/or semi-
permanent dermal fillers in the midfacial region. 
• 
Previous lower-eyelid and/or malar-region treatments with any dermal 
fillers (e.g., collagen, hyaluronic acid (HA), calcium hydroxyapatite, 
poly L-lactic acid (PLLA)) within the past 24 months. 

Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
M930121002 
Version 5.0, 04-NOV-2021 
CONFIDENTIAL AND PROPRIETARY 
Page iii of iii 
• 
Tendency to accumulate fluid in the lower eyelids, has developed 
festoons, or has large and/or herniating infraorbital fat pads. 
Duration of 
Treatment 
Subjects will have a screening period of up to 10 days and participate for a 
maximum duration of 76 weeks (± 14 days). 

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C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 of 1 1 1  
3 
T A B L E  O F C O N T E N T S  
1  
TI T L E P A G E  .............................................................................................................. 1 
2  
S Y N O P SI S  ................................................................................................................... i 
3  
T A B L E O F C O N T E N T S  ........................................................................................... 7 
3. 1  
List of I n -Te xt Ta bles  ............................................................................................ 1 1 
3. 2  
List of I n - Te xt Fi g ur es ........................................................................................... 1 1 
4  
LI S T  O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S  ....................... 1 2 
5  
E T HI C S  ..................................................................................................................... 1 6 
5. 1  
Et hical C o n d uct of t he St u d y ................................................................................. 1 6  
5. 2  
I nf or me d C o nse nt................................................................................................... 1 6 
5. 3  
C o nfi de ntialit y of S u bject I nf or mati o n  .................................................................. 1 7 
6  
I N T R O D U C TI O N .................................................................................................... 1 8 
6. 1  
Bac k gr o u n d a n d Rati o nal e ..................................................................................... 1 8  
6. 2  
P ote ntial Be nefits a n d Ris ks  .................................................................................. 1 8 
7  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S  .......................................................... 2 0 
7. 1  
O bjecti ves  .............................................................................................................. 2 0 
7. 2  
E n d p oi nts ............................................................................................................... 2 0  
7. 2. 1  
Effecti ve n ess E n d p oi nts ................................................................................... 2 0  
7. 2. 1. 1  
Pri m ary Effective n ess E n d p oi nt  ................................................................. 2 0 
7. 2. 1. 2  
Sec o n d ary Effective ness E n d p oi nts............................................................ 2 0  
7. 2. 2  
Safet y E n d p oi nts .............................................................................................. 2 2  
7. 2. 2. 1  
Sec o n d ary S afety E n d p oi nts ....................................................................... 2 2  
8  
C LI NI C A L I N V E S TI G A TI O N P L A N  ................................................................... 2 3 
8. 1  
O ver vie w of St u d y Desi g n ..................................................................................... 2 3  
8. 2  
Disc ussi o n of St u d y Desi g n, I n cl u di n g t he C h oice of C o ntr ol Gr o u ps ................. 2 5  
8. 3  
Defi niti o ns .............................................................................................................. 2 6 
8. 3. 1. 1  
S u bject E nr oll me nt a n d R a n d o miz ati o n..................................................... 2 6  
8. 3. 1. 2  
E n d of St u dy ............................................................................................... 2 6  
9  
S T U D Y P O P U L A TI O N A N D R E S T RI C TI O N S  .................................................. 2 7 
9. 1  
N u m ber of S u bjects a n d Sites ................................................................................ 2 7  
9. 2  
Selecti o n of S u bject P o p ulati o n ............................................................................. 2 7  
9. 2. 1  
I n cl usi o n Criteria ............................................................................................. 2 7 
9. 2. 2  
E xcl usi o n Criteria  ............................................................................................ 2 8 
9. 2. 3  
S u bject Restricti o ns d uri n g t he St u d y .............................................................. 3 0  
9. 2. 4  
Scree n Fail ures  ................................................................................................. 3 1 
9. 2. 5  
S u bjec t Wit h dra wal .......................................................................................... 3 1 
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C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 8 of 1 1 1  
9. 2. 6  
Re m o val of S u bjects fr o m T hera p y or Assess me nt ......................................... 3 2  
9. 2. 6. 1  
Tre at me nt Disc o nti n u ati o n ........................................................................ 3 2  
9. 2. 6. 2  
S u bject Disc o nti n u ati o n ............................................................................. 3 2  
9. 2. 6. 3  
Pr ovisi o n of C are f or S u bjects after St u dy Disc o nti n u ati o n ...................... 3 3  
9. 2. 7  
Pre mat ure S us pe nsi o n or Ter mi nati o n  of t he St u d y ........................................ 3 3 
9. 2. 8  
St u d y Site Disc o nti n uati o n .............................................................................. 3 4  
1 0  S T U D Y D E VI C E A N D T R E A T M E N T O F S U B J E C T S  ...................................... 3 5 
1 0. 1  
Descri pti o n of St u d y De vice .................................................................................. 3 5  
1 0. 1. 1  
I n v esti gati o nal Me dical De vice ....................................................................... 3 5 
1 0. 2  
I nstr u cti o ns f or Use a n d A d mi nistrati o n ................................................................ 3 5 
1 0. 3  
Met h o ds of Assi g ni n g S u bjects t o Treat me nt Gr o u ps ........................................... 3 5  
1 0. 5  
St u d y Treat me nt ..................................................................................................... 3 6  
1 0. 5. 1  
Pla n ne d Treat me nt Re gi me n  ............................................................................ 3 6 
1 0. 5. 1. 1  
I O H Tre at me nt Re gi o n ............................................................................... 3 6 
1 0. 5. 1. 2  
Tre at me nt A d mi nistr ati o n Pr oce d ure ........................................................ 3 7  
1 0. 6  
Pre vi o us a n d C o nc o mita nt N o n- dr u g T hera pies .................................................... 4 4  
1 0. 7  
St u d y S u p plies a n d Pac ka gi n g of Treat me nt S u p plies  .......................................... 4 4 
1 0. 8  
Recei pt, St ora ge, Dis pe nsi n g, a n d Ret ur n/ Dis p osal .............................................. 4 5  
1 0. 9  
De vice A cc o u nta bilit y Pr oce d ures  ......................................................................... 4 6 
1 0. 1 0  Treat me nt C o m plia nce ........................................................................................... 4 6  
1 0. 1 1  D urati o n of St u d y ................................................................................................... 4 6  
1 1  S T U D Y P R O C E D U R E S  .......................................................................................... 4 8 
1 1. 1  
Visit Sc he d ule  ........................................................................................................ 4 8 
1 1. 2  
St u d y Assess me nts a n d Defi niti o ns ....................................................................... 4 8  
1 1. 2. 1  
Effecti ve n ess Assess me nts ............................................................................... 4 8 
1 1. 2. 1. 1  
Merz I nfr a or bit al H oll o w Assess me nt Sc ale ( MI H A S) .............................. 4 8  
1 1. 2. 1. 2  
P h ot o gr a p hs ............................................................................................... 5 0  
1 1. 2. 1. 3  
Tre ati n g I nvesti g at or Gl o b al Aest hetic I m pr ove m e nt Sc ale ( G AI S).......... 5 1  
1 1. 2. 1. 4  
S u bject Gl o b al Aest hetic I m pr ove m e nt Sc ale ( G AI S)  ................................ 5 2 
1 1. 2. 1. 6  
P ai n Vis u al A n al o g ue Sc ale ( P ai n V A S) .................................................... 5 4  
1 1. 2. 1. 7  
Likeli h o o d of Retre at me nt S urvey .............................................................. 5 5  
1 1. 2. 2  
Safet y Assess me nts  .......................................................................................... 5 5 
1 1. 2. 2. 1  
Sec o n d ary S afety Assess me nts ................................................................... 5 6  
1 1. 3  
M o dificati o ns t o St u d y Pr oce d ures D uri n g a Pa n d e mic ........................................ 6 2  
1 2  S A F E T Y D E FI NI TI O N S A N D R E P O R TI N G R E Q UI R E M E N T S  .................... 6 4 
1 2. 1  
Defi niti o n of a n A d verse E ve nt ( A E) .................................................................... 6 4  
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C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 9 of 1 1 1  
1 2. 1. 1  
Details of a n A E  ............................................................................................... 6 4 
1 2. 1. 2  
Re p orti n g a n d Ha n dli n g of a n A E ................................................................... 6 4  
1 2. 1. 3  
Se verit y Gra di n g f or a n A E ............................................................................. 6 5  
1 2. 1. 4  
Ca usal Relati o ns hi p of a n A E wit h a n I n vesti gati o nal Me dical De vi ce .......... 6 5  
1 2. 1. 5  
O utc o me Cate g ories f or a n A E  ........................................................................ 6 6 
1 2. 2  
Defi niti o n of a Seri o us A d verse E ve nt ( S A E) ....................................................... 6 6  
1 2. 2. 1  
Details of a n S A E ............................................................................................. 6 7 
1 2. 2. 2  
Re p orti n g a n d Ha n dli n g of a n S A E ................................................................. 6 7  
1 2. 3  
Defi niti o n of a n A d verse De vice Effect ( A D E) ..................................................... 6 8  
1 2. 4  
Defi niti o n of a Seri o us A d verse D e vice Effect  ( S A D E) ....................................... 6 9 
1 2. 4. 1  
Defi niti o n of a n A ntici pate d Seri o us A d verse De vice Effect ( A S A D E)  ......... 6 9 
1 2. 4. 2  
Defi niti o n of a n U na ntici pate d A d vers e De vi ce Effect ( U A D E)  .................... 6 9 
1 2. 5  
Defi niti o n of De vice Deficie nc y  ............................................................................ 6 9 
1 2. 6  
Defi niti o n of Tec h nical C o m plai nt ........................................................................ 6 9  
1 2. 6. 1  
Re p orti n g a n d Ha n dli n g of De vice Defi cie ncies ............................................. 7 0  
1 2. 7  
Vis ual Safet y E val uati o n ........................................................................................ 7 0 
1 2. 9  
Re p orti n g of Pre g na nc y ......................................................................................... 7 1  
1 3  S T A TI S TI C A L M E T H O D S  .................................................................................... 7 2 
1 3. 1  
Ra n d o mizati o n ....................................................................................................... 7 2  
1 3. 2  
Esti mati o n of Sa m ple Size  ..................................................................................... 7 3 
1 3. 3  
P o p ulati o ns f or A nal ysis ........................................................................................ 7 4  
1 3. 4  
A nal ysis of St u d y Data  .......................................................................................... 7 5 
1 3. 4. 1  
Effecti ve n ess A nal yses  .................................................................................... 7 5 
1 3. 4. 1. 1  
Pri m ary Effective n ess E n d p oi nt  ................................................................. 7 6 
1 3. 4. 1. 2  
Sec o n d ary Effective ness E n d p oi nts............................................................ 7 9  
1 3. 4. 2  
Safet y A nal yses  ................................................................................................ 8 3 
1 3. 4. 3  
Ot her S u bject Data  ........................................................................................... 8 5 
1 3. 5  
S pecial Statistical/ A nal ytical Iss u es  ..................................................................... 8 6 
1 3. 5. 1  
S u bject Disc o nti n uati o n a n d Missi n g Data ...................................................... 8 6  
1 3. 5. 2  
I nteri m A nal yses .............................................................................................. 8 6 
1 3. 5. 3  
Ot her Pla n ne d or S u b gr o u p A nal yses .............................................................. 8 6  
1 4  A D MI NI S T R A TI V E P R O C E D U R E S  .................................................................... 8 7 
1 4. 1  
St u d y M o nit ori n g ................................................................................................... 8 7  
1 4. 2  
Data Q ualit y Ass ur a nce  ......................................................................................... 8 7 
1 4. 2. 1  
Sta n dar dizati o n Pr oce d ures  .............................................................................. 8 8 
1 4. 2. 2  
S o urce D oc u m e ntati o n Re q uire me nts.............................................................. 8 8  
1 4. 2. 3  
Data Ma na g e me nt  ............................................................................................ 8 9 
1 4. 2. 4  
A u diti n g ........................................................................................................... 9 0  
1 4. 3  
Rec or d Rete nti o n  ................................................................................................... 9 0 
1 4. 4  
P u blicati o n P olic y  .................................................................................................. 9 1 
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C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 1 0  of 1 1 1  
1 4. 5  
Fi na ncial Discl os ur e ............................................................................................... 9 2 
1 4. 6  
I n v esti gat or C o m plia nce ........................................................................................ 9 2 
1 5  R E F E R E N C E LI S T .................................................................................................. 9 3 
1 6  A P P E N DI C E S  ........................................................................................................... 9 4 
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Merz N ort h A merica, I nc.  
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C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 1 1  of 1 1 1  
3. 1  
Li st  of I n-T e xt T a bl e s  
3. 2  
Li st  of I n-T e xt Fi g ur e s  
 
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Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
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Page 15 of 111 
Definitions of Terms 
Clinical Study Protocol 
The use of the term “Clinical Study Protocol (CSP)” is synonymous with the term “Clinical 
Investigational Plan (CIP)”. 
Early study termination 
Study halted prematurely and did not resume; subjects were no longer examined or treated. 
Effectiveness 
The use of the term “effectiveness” is synonymous with the term “clinical performance”. 
Investigational medical device 
The terms “investigational medical device” is synonymous with the term “investigational 
device”. 
Rater 
The term “rater” is synonymous with the term “evaluator”. 
Study 
The term “study” is synonymous with the term “investigation”. 

Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
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Page 16 of 111 
5 ETHICS 
5.1 
Ethical Conduct of the Study 
This study will be performed in accordance with the principles outlined in the Declaration 
of Helsinki and in compliance with the standards for Good Clinical Practice described in 
EN ISO 14155, the Code of Federal Regulations, and any applicable regional or national 
laws and regulations. The study will adhere to all applicable subject privacy requirements. 
All required approvals, favorable opinions, or additional requirements of the appropriate 
Independent Ethics Committee (IEC), Institutional Review Board (IRB), or other 
regulatory authority will be obtained prior to initiation of the trial. 
The investigator and all study personnel will conduct the study in compliance with this 
protocol. The investigator will ensure that all personnel involved in the conduct of this 
study are qualified to perform the assigned study responsibilities. Investigators will adhere 
to all applicable study reporting requirements. 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), procedures that prioritize the reporting of protocol deviations that could 
impact subject safety will be defined and communicated to the appropriate IEC/IRB. 
In addition, changes in protocol conduct necessary to ensure subject safety, such as 
conducting telephone or virtual visits for safety monitoring rather than on-site visits, can 
be implemented immediately with subsequent review by the IEC/IRB and notification to 
regulatory authorities. 
5.2 
Informed Consent 
Written informed consent must be obtained from every subject prior to the initiation of any 
screening or study procedures. The investigator will follow a standard process for obtaining 
consent that complies with all applicable regulatory requirements. The original and any 
amended signed and dated informed consent form (ICF) must be retained at the study site, 
and a copy must be given to the subject. 
It is not anticipated that members of a vulnerable population will participate in this study. 
If the ICF is amended during the study, the investigator must follow all applicable 
regulatory requirements pertaining to approval of the amended ICF by the IEC/IRB and 
use of the amended form (including for ongoing subjects, if required). 
During the study, the subject will be informed in a timely manner if information becomes 
available that may be relevant to the subject’s willingness to continue participation in the 
study. If an adverse event (AE) should occur, the subject should inform the investigator, 

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who then will make a judgment whether continuing in the study serves the subject’s best 
interests. The subject, however, is free to withdraw consent at any time and for any reason, 
whether expressed or not. 
Each ICF will include contact information (with a phone number) for the investigator and 
an ophthalmology practice; the subject should use this information to communicate any 
medical concerns 24 hours a day. 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), if re-consenting of the subjects is deemed necessary due to significant changes 
made to the protocol and/or monitoring plan that could impact subjects, then: 
• Alternative ways of obtaining consent will be defined as subjects should not visit 
sites for the sole purpose of obtaining re-consent. For example, subjects will be 
contacted via phone or video calls to provide verbal consent supplemented with 
written (e.g., e-mail) confirmation. 
• The IEC/IRB approved, updated subject information sheet and consent form will 
be provided by e-mail, mail, or courier to obtain a re-consent. 
• All instances of consent that is obtained through alternative ways will be 
documented. 
The subjects’ understanding will be re-confirmed through regular consent procedures at 
the earliest opportunity when/if the subjects are able to return to the sites, if applicable. 
5.3 
Confidentiality of Subject Information 
Subject pseudo-anonymity is to be maintained during the study. Subjects will be identified 
by a unique subject number on all study documentation. Non-pseudonymized documents 
must be maintained in strict confidence by the investigator to the extent permitted by 
applicable laws and regulations, unless their disclosure is necessary to allow auditing by 
regulatory authorities, the sponsor, or the sponsor’s designee. 
Subject medical information obtained during the study is confidential. At a subject’s 
request, the subject’s medical information may be provided to the subject’s personal 
physician or other appropriate medical personnel. Disclosure of subject medical 
information to third parties other than those noted above is not permitted. 

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6 INTRODUCTION 
6.1 
Background and Rationale 
There is increasing interest among patients to seek minimally invasive alternatives to 
aesthetic surgical procedures to improve the appearance of the face. Because of the aging 
process, a noticeable concave deformity may develop in the under-eye area; this hollowing 
of the infraorbital region results in a fatigued and aged appearance on the face. While many 
anatomical and physiological factors must be considered as contributing to infraorbital 
hollowing, subjects with an inherent level of volume loss may benefit from dermal-filler 
augmentation. However, treating the infraorbital hollow (IOH) may present challenges, 
and only a few fillers are suitable for this area. 
To address the aforementioned issues, the objectives of this study will be to demonstrate 
the effectiveness and safety of Belotero Balance® (+) Lidocaine (BBL) injection for the 
treatment of volume loss in the infraorbital hollow area in a scientifically robust and 
adequately powered pivotal study. 
6.2 
Potential Benefits and Risks 
The potential benefit of BBL is the correction of volume loss in the IOH area. In a pilot 
study conducted using Belotero Balance (M930121001; A Pilot Study to Assess the 
Effectiveness and Safety of Belotero Balance Injection for Volume Augmentation of the 
Infraorbital Hollow), the majority of treated subjects achieved at least 1-point improvement 
on the Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8 (81.6% of treated 
subjects; p < 0.0001). The findings also demonstrated aesthetically pleasing outcomes with 
strong agreement between the blinded MIHAS evaluators and Global Aesthetic 
Improvement Scale (GAIS) assessments completed by both the treating investigator and 
the subject. FACE-Q™ assessments assessing satisfaction with eyes and lower eyelids 
improved over time after injection with Belotero Balance. Additionally, treated subjects 
reported looking younger after treatment when compared to untreated subjects. 
The following are AEs that have been reported during post-approval use of Belotero 
Balance1 : allergic reactions including Quincke’s edema, anaphylaxis, rash, hives, necrosis, 
inflammation, granuloma, indurations, papule/nodule, hematoma, Tyndall effect, 
bumps/lumps, pustule, scabbing/scarring, swelling/edema, erythema/redness, pain, 
bruising, discoloration, infection, migration/displacement, asymmetry, numbness, 
itching/pruritus, vascular occlusion, and visual disturbance. 
 
1 Belotero Balance (BB) and Belotero Balance (+) Lidocaine (BBL) are the same formulation with the 
exception that lidocaine hydrochloride is added to the BBL formulation. Belotero Balance has been 
commercially available in the US since 2011 for the treatment of mid-to-deep dynamic and static wrinkles 
and folds, such as nasolabial folds. The events listed in this section were reported during post-approval use. 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 1 9  of 1 1 1  
P ote ntial ris ks ass ociate d wit h t he use of B B L are si milar t o t h ose of ot her c o m merciall y 
a vaila ble, dee p s oft -tiss u e fillers. Pre vi o usl y re p orte d i njecti o n-site res p o nses t o Bel oter o 
Bala nce  c o nsiste d  mai nl y  of  s h ort -t er m  i nfla m mat or y  s y m pt o ms  i ncl u di n g:  s welli n g,  
i n d urati o n, br uisi n g, re d n ess, er yt he m a, pai n, n o d ule f or mati o n, disc ol orati o n, pr urit us, a n d 
ras h. T hese o bs er vati o ns be ga n s o o n aft er treat me nt a n d res ol ve d wit hi n 1 4 da ys or less. 
Alt h o u g h r are, s eri o us a d verse e v e nts ( S A Es) ass ociate d wit h t he i ntra v asc ular i njecti o n of 
s oft-tiss ue fillers i n t he face h ave b ee n re p ort e d a n d i ncl u de: te m p orar y or per ma ne nt visi o n 
i m pair me nt; bli n d ness; cere br al isc h e mia or cere bral he m orr ha g e lea di n g t o str o ke; s ki n 
necr osis; a bscess es; gra n ul o mas; e yeli d m uscle de ge nerati o n; e y eli d pt osis ; a n d da ma ge t o 
t he u n derl yi n g faci al str uct ures. I m pla ntati o n of fat cells or a n y s oft-tiss ue filler i nt o t he 
vasc ulat ure m a y lea d t o e m b olizati o n, occl usi o n of t he vessels, isc he mia, or i nfarcti o n. 
Li d ocai ne is c o m merciall y a vaila ble a n d fre q ue ntl y use d as a l ocal a n d re gi o nal a nest hetic  
a ge nt. P ote ntial si de effects a ntici pate d wit h its use i ncl u de: li g ht hea de d ness; ner v o us ness; 
a p pre he nsi o n; e u p h oria; c o nf usi o n; dizzi ness; dr o wsi ness; ri n gi n g n oise i n t he ears; bl urre d 
or d o u ble visi o n; v o miti n g; se nsati o ns of heat, c ol d or n u m b ness; t w itc hi n g; tre m ors; 
c o n v ulsi o ns;  u nc o nsci o us ness;  res pirat or y  de pressi o n  a n d  arrest;  sl o w  heart b eat;  
h y p ote nsi o n; a n d car di o v asc ular c olla pse, w hic h ma y lea d t o car diac arrest. 
A n a d diti o nal ris k ass oci ate d wit h t he use of B B L i ncl u des disa p p oi nt me nt d ue t o l ac k of 
or less t ha n e x pecte d perf or ma nce a n d/ or u n desira ble aest hetic effect. 
T he use of a ca n n ula ma y i ncrease t he d urati o n of l ocal /site irritati o n or er yt he ma b y 1 t o 
2 da ys w he n  c o m p are d  t o t he use of a n ee dle. 
A  pil ot  st u d y  c o n d ucte d  usi n g  Bel oter o  Bala nce  i n  t he  I O H  area  ( M 9 3 0 1 2 1 0 0 1) 
de m o nstrate d a n acce pta ble A E pr ofile, wit h n o  treat me nt-relate d SA Es or u na ntici pate d 
a d verse d e vice effects ( U A D Es) re p orte d. Ma n y  c o m m o n treat me nt res p o nses ( C T Rs ) 
res ol ve d wit hi n 1 t o 1 4 da ys p ost i njecti o n a n d pri or t o a f oll o w-u p visit. N o A Es were 
cate g orize d as u ne x p ecte d or at y pical wit h  use of Bel oter o Bala nce i n t he I O Hs. N o e ve nts 
ass ociate d wit h reti nal -arter y occl usi o n or vis ual dist ur ba nce , or  t he lat e o nset of s uc h 
e ve nts relat e d t o Bel oter o Bala nce i n t he I O H re gi o n  were re p orte d . 
C urre ntl y,  n o  der m al  fillers  are  a p pr o v e d  f or  v ol u me  c orrecti o n  ar o u n d  t he e yes.  
Alter nati ve i nter v e nti o ns ma y  i ncl u de  v ari o us  s ur gical  a n d  n o n -i n vasi ve  pr oce d ures, 
p ote ntial t o pical t hera p ies, or n o treat me nt at all . 
A d diti o nal i nf or mati o n o n pr o d uct - a n d i njecti o n -relate d c o ntrai n dicati o ns, war ni n gs, a n d 
preca uti o ns ca n be f o u n d i n Secti o n s 1 0. 1  a n d 1 0. 5. 1. 2 ,C CI

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7 STUDY OBJECTIVES AND ENDPOINTS 
7.1 
Objectives 
Effectiveness 
Confirm the effectiveness of BBL injection for the correction of volume loss in the IOH 
area by demonstrating superiority to untreated control. 
Safety 
Confirm the safety of BBL injection for the correction of volume loss in the IOH area. 
7.2 
Endpoints 
7.2.1 
Effectiveness Endpoints 
7.2.1.1 
Primary Effectiveness Endpoint 
Proportion of responders at Week 8 on the MIHAS, as assessed live by a blinded evaluator. 
Note: Responder is defined as a subject with at least 1-point improvement from baseline 
on MIHAS of both IOHs. 
Note: For subjects randomized to treatment, if no touch-up is performed, the primary 
effectiveness MIHAS assessment will occur 8 weeks post baseline injection. If a touch-up 
is performed, the primary effectiveness MIHAS assessment will be completed 8 weeks post 
touch-up. For subjects randomized to control/delayed-treatment, the primary effectiveness 
assessment will occur 8 weeks from the screening visit. 
7.2.1.2 
Secondary Effectiveness Endpoints 
Note: For all secondary endpoints, Week 8 corresponds to the time from last injection 
(either baseline or touch-up injection) for subjects randomized to treatment only (TN and 
TC groups). 
• GAIS score at Week 8, as assessed by the treating investigator. 
• GAIS score at Week 8, as assessed by the subject. 
• FACE-Q™ Satisfaction with Eyes scores and changes from baseline to Week 8, as 
assessed by the subject. 
Note: FACE-Q evaluates both eyes concurrently. 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 1  of 1 1 1  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 2  of 1 1 1  
7. 2. 2  
S af et y E n d p oi nt s 
7. 2. 2. 1  
S e c o n d ar y S af et y E n d p oi nt s  
•  I n ci de nce of treat me nt-e mer ge nt a d verse e v e nts ( T E A Es) rel ate d t o B B L . 
•  I n ci de nce of treat me nt-e mer ge nt seri o us a d v erse e ve nts ( T E S A Es) relate d t o B B L . 
C CI
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 3  of 1 1 1  
8 
C LI NI C A L I N V E S TI G A TI O N P L A N  
8. 1  
O v er vi e w of S t u d y D e si g n  
T his is a pr os pecti ve, m ultice nter, ra n d o mize d, c o m parati ve, e val u at or- bli n de d  pi v otal 
st u d y desi g ne d t o e v al uat e t he s afet y a n d effecti ve ness of B B L  f or t he c orrecti o n of v ol u me 
l oss i n t he I O H. St u d y su bjects  will ha v e a scree ni n g peri o d of u p t o 1 0  d a ys a n d p artici pate 
f or a ma xi m u m d urati o n of 7 6 wee ks  ( ± 1 4 da ys). 
A t otal of 1 5 0 s u bjects will be ra n d o mize d at u p t o 9 i n vesti gati o nal sit es i n t he U nite d 
States ( U S) . At eac h st u d y site, t he n u m ber of s u bjects ra n d o mize d s h o ul d n ot e xcee d 2 6. 
A mi ni m u m of 2 0 % of e nr olle d s u bjects will be Fitz patric k S ki n T y pe I V, V , or VI  
 
S u bjects fr o m t he Fitz patric k S ki n 
T y pe I V, V, or VI gr o u p will be distri b ute d as f oll o ws: at least 1 6 s u bjects of T y pe I V; 
7 s u bjects of T y pe V; a n d 7 s u bjects of T y pe VI. At least 1 0 % of t he s u bjects e nr olle d will 
be male.  
S u bjects eli gi ble f or st u d y e nr oll me nt will ha ve s y m metrical ri g ht a n d left I O Hs wit h t he 
sa me MI H A S sc ore of 2 or 3 ( m o derate or se vere), as assesse d li ve b y a bli n de d e val uat or . 
All  bli n de d e val uat ors will be  q ualifie d healt hcare practiti o ner s, d ele gate d b y t he treati n g 
i n vesti gat or a n d trai ne d b y t he s p o ns or. At scree ni n g, eli gi ble s u bjects will be ra n d o mize d 
t o 4 gr o u ps usi n g a 2: 2: 1: 1 rati o as f oll o ws: B B L  wit h nee dle  (T N ), B B L  wit h ca n n ula  
(T C ), c o ntr ol/dela ye d -treat me nt B B L  wit h nee dle ( CD T N ), a n d c o ntr ol/del a ye d -treat me nt 
B B L  wit h ca n n ula   ( CD T C ).  The nee dle or ca n n ula assi g n me nt f or a s u bject ca n n ot be 
i nterc ha n ge d d uri n g t he st u d y ; t hat is, nee dle a n d ca n n ula ca n n ot be use d i n t he sa me 
s u bject. 
S u bjects  ra n d o mize d t o treat me nt will recei ve a B B L  i njecti o n i n b ot h I O Hs  at Da y 1 . 
Treate d  s u bjects  w h o  d o  n ot  ac hie v e o pti mal  aest hetic  c orrecti o n  or  at  least  1- p oi nt 
i m pr o ve me nt o n t he MI H A S , as assesse d b y t he bli n de d e val uat or 4 wee ks p ost treat me nt  
c o m pare d t o b aseli ne , m a y ha ve a t o uc h -u p i njecti o n i n o ne or b ot h I O H(s). If a t o uc h- u p 
is necessar y, it will o nl y be a d mi nistere d if t here are n o m e dical c o ntrai n dicati o n s or 
e xisti n g A E s of  c o ncer n , as  deter mi ne d  b y  t he  treati n g  i n vesti gat or.  T he  treati n g  
i n vesti gat or will be res p o nsi ble f or re vie wi n g w h et her t he t hres h ol d f or o pti mal aest hetic 
c orrecti o n or at least 1- p oi nt MI H A S i m pr o ve m e nt is met , as ass esse d b y t he bli n de d 
e val uat or, si nce t he bli n de d e val uat or will n ot ha ve access t o t he s u bject’s st u d y rec or ds. 
S u bjects w h o ac hie ve at l east 1 -p oi nt i m pr o ve m e nt o n t he MI H A S 4 wee ks p ost treat me nt  
w he n c o m pare d t o baseli ne ma y ha ve a t o uc h- u p i njecti o n in o ne or b ot h I O H(s) t o ac hie ve 
o pti mal c orrecti o n , at t he discreti o n of t he treati n g i n vesti gat or a n d t he s u bject. 
S u bjects ra n d o mize d t o treat me nt at Da y 1 will ha ve t he o pti o n f or retreat me nt, u p o n 
a gree m e nt bet wee n t he s u bject a n d t he treati n g i n vesti gat or, at 4 8 wee ks p ost last i njecti o n 
C CI
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 4  of 1 1 1  
(i.e.,  baseli ne  i njecti o n  or  t o uc h-u p,  if  a p plica ble)  a n d  will  t he n  be  f oll o we d  f or  a n  
a d diti o nal 2 4 wee ks, f or a t otal st u d y d urati o n of u p t o 7 6 wee ks ( 7 2 wee ks if n o t o uc h- u p 
is perf or me d). 
S u bjects ra n d o mize d t o t he c o ntr ol/dela ye d -treat me nt gr o u p will re mai n u ntreate d u ntil 
Wee k 8. After all a p plica ble effecti ve ness  e n d p oi nt assess me nts ha ve bee n c o m plete d  at 
t heir Wee k  8  visit,  c o ntr ol  s u bjects  will  recei ve B B L  I O H  i njecti o ns  (i.e., dela ye d 
treat me nt) a n d  will  be  f oll o we d  f or  4 8  wee ks.  S u bjects  w h o  d o  n ot  ac hie ve  o pti mal 
aest hetic c orrecti o n or at least 1 - p oi nt i m pr o ve me nt o n t he MI H A S as assesse d b y t he 
bli n de d e val uat or 4 w ee ks p ost treat me nt  c o m p are d t o t he  d ela ye d-treat me nt baseli ne  
( Wee k 8), ma y  ha ve a t o uc h -u p i njecti o n i n o ne or b ot h I O H(s ). If a t o uc h-u p is necessar y, 
it will o nl y be a d mi nistere d if t here are n o me dical c o ntrai n dicati o ns or e xisti n g A E s of 
c o ncer n, as  det er mi ne d  b y  t he  treati n g  i n vesti g at or.  T he  treati n g  i n vesti gat or  will  be  
res p o nsi ble f or re vie wi n g w het her t he t hres h ol d f or o pti mal aest hetic c orrecti o n or at least 
1- p oi nt MI H A S i m pr o ve me nt is met , as assesse d b y t he bli n de d e val uat or , si nce t he bli n de d 
e val uat or will n ot ha ve access t o t he s u bject’s st u d y rec or ds. 
S u bjects  w h o ac hie ve at l east 1- p oi nt i m pr o ve m e nt o n t he MI H A S 4 wee ks p ost treat me nt  
w he n c o m pare d t o t he dela ye d -treat me nt baseli ne ( Wee k 8) m a y ha v e a t o uc h - u p i njecti o n 
in o ne or b ot h I O H(s) t o ac hie ve o pti mal c orrecti o n , at t he discreti o n of t he treati n g 
i n vesti gat or a n d t he s u bject. 
C o ntr ol/ dela ye d- treat me nt s u bjects will n ot be offere d retreat me nt. 
A n y ti me a s u bject is treate d (i.e., i nitial i njecti o n, t o uc h -u p, a n d/ or retreat me nt), he/s he 
will ha ve a 7 2 -h o ur p ost -treat me nt p h o ne call t o e val uate safet y. If a s u bject re p orts a safet y 
c o ncer n d uri n g a n y p h o n e call, a n u nsc h e d ule d visit ma y be necessar y. 
Effecti ve n ess assess me nts i ncl u de bli n de d e val uat or MI H A S , treati n g i n vesti gat or a n d 
s u bject G AI S, s u bject-r e p orte d F A C E-Q Satisfacti o n  wit h E yes , F A C E -Q A p prais al of 
L o wer E yeli ds , F A C E -Q Patie nt - Percei ve d A g e V A S , a Patie nt-Percei ve d Pai n V A S , a n d 
a  li keli h o o d  of  f ut ur e  treat me nt  assess m e nt .  T hese  ass ess me nts  will  be  perf or me d  
t hr o u g h o ut t he st u d y. A d diti o nall y, t hree bli n de d , b oar d-certifie d I P R e x perts w h o are n ot 
part of t he st u d y sites will assess s u bject I O Hs usi n g t he MI H A S a n d s u bject p h ot o gra p hs. 
Sta n dar d safet y para met ers will be m o nit ore d t hr o u g h o ut t he st u d y. A d diti o nall y, vis ual 
assess me nts (i.e., vis ual ac uit y, c o nfr o nt ati o n vis ual fiel d test, oc ular m otilit y, a n d a n 
u n dilate d ce ntral reti nal e xa m usi n g n o n -m y driati c reti nal ca meras a n d rea d b y a ce ntral 
rea der) will be c o n d uct e d. A s u bject e Diar y w ill be use d t o rec or d pre defi ne d C T Rs f or 
2 8 da ys after t he i nitial i njecti o n, t o uc h -u p i njecti o ns (if a p plica bl e), a n d retreat me nt (if 
a p plica ble).  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 5  of 1 1 1  
8. 2  
Di s c u s si o n of St u d y D e si g n, I n cl u di n g t h e C h oi c e of C o ntr ol Gr o u p s  
As detaile d i n Secti o n 8. 1 , t his is a pr os pecti ve, m ultice nter, ra n d o mize d, c o m parati ve, 
e val uat or- bli n de d, pi v otal st u d y desi g ne d t o e val uate t he effecti ve ness a n d safet y of B B L  
f or t he c orrecti o n of v ol u me l oss i n t he I O H area. 
Si nce  n o a p pr o ve d , mar k e ted pr o d ucts are c urre ntl y a vaila ble i n t he U S f or treat me nt of 
t he I O H r e gi o n, a n u ntr eate d -c o ntr ol gr o u p will be utilize d f or t his st u d y . To ma xi mize t he 
n u m ber of s u bjects e x p ose d f or ge nerati o n of a d e q uate safet y data, c o ntr ol s u bjects will 
recei v e  dela ye d  treat me nt  wit h  B B L  u p o n  c o m pleti o n  of  all Wee k  8  effecti ve n ess 
assess me nts.  
As  s u bject satisf acti o n is t he pri mar y g oal of aest hetic me dici ne, s u bjects ma y u n der g o a 
t o uc h-u p
 treat me nt
 after
 i nitial
 i njecti o n
 t o
 ac hie ve
 o pti mal
 c orrecti o n . 
S u bjects  ra n d o mize d t o tr eat me nt will als o be eli gi ble f or retreat me nt at 4 8 wee ks  p ost last 
i njecti o n  (i.e.,  baseli ne  i njecti o n  or  t o uc h-u p,  if  a p plica ble)  f or  f urt her  aest hetic  I O H 
e n ha nce me nt. O pti o n al r etreat me nt will hel p  i m pr o ve c o m plia nce wit h t he st u d y pr ot oc ol 
(i.e., mi ni mize earl y disc o nti n uati o n) a n d e ns ure s u bjects will c o m plete t he st u d y wit h 
aest hetic I O H i m pr o ve m e nt. Retreati n g s u bjects at 4 8 wee ks p ost last i njecti o n will als o 
pr o vi de a d diti o nal safet y data ass ociat e d wit h re peat treat me nt.  
I njecti o n v ol u mes t o be a d mi nistere d i n t his st u d y (see Secti o n 1 0. 5. 1. 2. 6 ) re prese nt a safe 
sta n dar d f or I O H treat me nt a n d are c o nsiste nt wit h v ol u mes utilize d i n a Bel oter o Bala n ce 
pil ot st u d y of I O H tr eat m e nt ( M 9 3 0 1 2 1 0 0 1). 
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8.3 
Definitions 
8.3.1.1 
Subject Enrollment and Randomization 
Subjects are considered to be enrolled when they sign informed consent and meet all 
eligibility criteria. Eligible subjects will be randomized at the screening visit. 
Screen failures are defined in Section 9.2.4. 
8.3.1.2 
End of Study 
The end of the study is defined as when the last subject completes the last visit and the 
database is closed. 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 7  of 1 1 1  
9 
S T U D Y P O P U L A TI O N A N D R E S T RI C TI O N S  
9. 1  
N u m b er of S u bj e ct s a n d Sit e s  
A t otal of 1 5 0 s u bjects will  be ra n d o mize d at u p t o 9 i n vesti gati o nal sites i n t he U S . At  eac h 
st u d y site, t he n u m ber of s u bjects ra n d o mize d s h o ul d n ot e xcee d 2 6. A mi ni m u m of 2 0 % 
of t he e nr olle d s u bjects will be Fitz p atric k S ki n T y pe I V, V, or  VI. S u bjects fr o m t he 
Fitz patric k S ki n T y pe I V, V, or VI gr o u p will be distri b ute d as f oll o ws: at least 1 6 s u bjects 
of T y pe I V ; 7 s u bjects of T y pe V ; a n d 7 s u bjects of T y pe VI. At least 1 0 % of t he s u bjects 
e nr olle d will be male.  
A n y ra n d o mize d s u bject w h o d oes n ot c o m plete t he st u d y will n ot be re place d.  
A d diti o nal i nf or mati o n r e gar di n g s u bject e nr oll m e nt is pr o vi de d wit hi n t h e sa m ple size 
j ustificati o n i n Secti o n  1 3. 2 . 
9. 2  
S el e cti o n of S u bj e ct P o p ul ati o n  
S electi o n  criteria  ha v e  bee n  c h ose n  t o  i de ntif y  a  s uita ble  p o p ulati o n  of  s u bjects  t o  
i n vesti gate st u d y o bjecti ves a n d t o mi ni mize safet y c o ncer ns i n t his p o p ulati o n. 
9. 2. 1  
I n cl u si o n C rit eri a 
T o be eli gi ble f or st u d y p artici pati o n, eac h s u bject m ust meet all of t he f oll o wi n g criteria:  
1.  Is a ca n di d ate f or bilat eral I O H treat me nt. 
2.  Has s y m metrical ri g ht a n d left I O Hs wit h t he sa m e MI H A S sc ore of 2 or 3 ( m o derate 
or se ver e) , as assesse d li ve b y t he bli n de d e val u at or. 
3.  Is ≥ 2 2 a n d ≤ 6 5 years ol d. 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 8  of 1 1 1  
9. 2. 2  
E x cl u si o n Crit eri a  
S u bjects meeti n g a n y of t he f oll o wi n g criteria are n ot eli gi ble t o partici pate i n t he st u d y:  
4.  Ha d  p ri or  l o w er-e yeli d  s ur ger y,  i ncl u di n g  or bital  or  mi dface  s ur ger y,  or  has  a  
per ma ne nt  i m pla nt  or  graft  i n  t he  mi dfacial  re gi o n  t hat  c o ul d  i nterfere  wit h  
effecti ve ness  assess me nts . N ote :  R hi n o plast y  is  per mitte d  if  t he  pr o ce d ure  was  
≥ 1 2 m o nt hs pri or t o st u d y e nr oll me nt. 
5.  Has e ver  bee n tr eate d wit h fat i njecti o ns or per ma ne nt a n d/ or se mi -per m a n e nt der mal 
fillers i n t he mi dfacial r e gi o n. 
6.  Has  recei ve d  l o wer -e yeli d  a n d/ or  malar -re gi o n  treat me nts  wit h  a n y  der mal fillers 
(e. g., c olla ge n, h y al ur o nic aci d ( H A) , calci u m h y dr o x ya patite , or p ol y L -lactic aci d 
( P L L A)) wit hi n t he past 2 4 m o nt hs. 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 2 9  of 1 1 1  
1 6.  Has a te n denc y t o acc u m ulate fl ui d i n t he l o w er e y eli ds, has de v el o pe d fest o o ns, or has 
lar ge a n d/ or h er niati n g i nfra or bital fat pa ds. 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 0  of 1 1 1  
9. 2. 3  
S u bj e ct R e stri cti o n s d uri n g  t h e S t u d y 
B y pr o vi di n g i nf or me d c o nse nt, s u bjects are als o pr o hi bite d fr o m t he f oll o wi n g acti o ns a n d 
treat me nts after i njecti o n : 
•  T o uc hi n g/ pressi n g t he treat me nt area f or 1 2 h o urs after treat me nt.  
•  A p pl yi n g ma ke u p t o t he treat me nt area f or 1 2 h o urs after treat me nt.  
•  E xercisi n g stre n u o usl y f or 2 4 h o urs after treat me nt.  
•  C o ns u mi n g alc o h olic be vera ges f or 2 4 h o urs after treat me nt.  
•  E x p osi n g t he treate d ar ea t o e xte nsi ve s u n or h eat e x p os ure  f or 2 4 h o urs after treat me nt. 
 
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• Receiving any other procedures (i.e., dermal fillers, fat injections, facial ablative or 
fractional laser, microderm abrasion, superficial or deep chemical peels, platelet-rich 
plasma, non-invasive skin-tightening [e.g., Ultherapy, Thermage], mesotherapy, or any 
surgical procedures) on ANY part of the face during study participation. 
• Receiving neurotoxin treatment in ANY part of the face. 
• Initiation of any new topical over-the-counter or prescription facial skin product or oral 
medication that affects the facial appearance. 
• Using prescription topical steroids on the face. 
• Receiving anti-coagulation, anti-platelet, or thrombolytic medications (e.g., warfarin), 
anti-inflammatory drugs (e.g., oral/injectable corticosteroids or NSAIDs [e.g., aspirin, 
ibuprofen]), or other substances known to increase coagulation time (e.g., vitamins or 
herbal supplements, [e.g., Vitamin E, fish oil, garlic, gingko, St. John’s Wort]) from 
10 days before injection to 3 days after injection. 
• Receiving 
immunosuppressive 
medications 
or 
systemic 
steroids 
(except 
intranasal/inhaled or intra-articular steroids). 
• Gaining or losing ≥ 2 BMI units. 
• Prolonged exposure of the face to UV radiation (sun, tanning bed). 
• Oral surgery (e.g., orthodontia, extraction, implants). 
9.2.4 
Screen Failures 
Subjects who sign informed consent but who do not meet eligibility criteria or who 
withdraw consent prior to being randomized in the electronic randomization system will 
be defined as screen failures. The investigator will maintain all source documentation for 
all subjects who are considered screen failures. Minimal information will be collected in 
the electronic data capture (EDC) system for screen failures, such as date of informed 
consent, demographics, and reason for screen failure. Individuals who do not meet the 
criteria for participation in this study may not be rescreened. 
9.2.5 
Subject Withdrawal 
A subject may withdraw from the study at any time at his/her own request without prejudice 
to future medical care. Subjects may also be withdrawn at any time at the discretion of the 
investigator for safety, non-compliance, or administrative reasons. 
If a subject does not attend a required study visit, the following actions will be taken: 
• The site will attempt to contact the subject at least twice and reschedule the missed visit 
as soon as possible. Every effort to regain contact with the subject will be made 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 2  of 1 1 1  
(e. g., tele p h o ne c o ntact o n differe nt dates/ti mes, re gistere d mail). All c o ntact atte m pts 
will be d oc u me nte d. 
•  If atte m pts t o c o nt act t he s u bject are n ot s uccessf ul, t he s u bject will b e c o nsi dere d l ost 
t o f oll o w- u p a n d wit h dra w n fr o m t he st u d y. 
T he reas o n f or earl y wit h dra wal s h o ul d b e d o c u me nte d i n t he electr o nic case re p ort f or m 
(e C R F). T he  i n v esti gat or  s h o ul d  ma ke  e ver y  atte m pt  t o  c o m plete  t he  rec o m me n de d  
f oll o w-u p assess me nts s p ecifie d f or t he last st u d y visit.  
I n cas es of wit h dra w n c o nse nt, data c ollecte d u ntil t he date c o nse nt was wit h dra w n will be 
a nal yze d as rec or de d . 
9. 2. 6  
R e m o v al of S u bj e ct s fr o m T h er a p y or A s s e s s m e nt  
9. 2. 6. 1   
Tr e at m e nt D i s c o nti n u ati o n 
If st u d y treat me nt is disc o nti n ue d at a n y ti me d uri n g t he st u d y, t he i n vesti gat or will rec or d 
t he reas o n f or treat me nt disc o nti n uati o n i n t he st u d y rec or ds. T he i n vesti gat or s h o ul d 
re q uest t hat a s u bject disc o nti n ui n g treat me nt c o nti n ue t o partici pate i n t he st u d y a n d 
c o m plete all re mai ni n g visits a n d assess me nts. If a s u bject decli nes t o c o nti n ue st u d y 
partici pat i o n,  t he  i n vesti gat or  will  ma ke  e v er y  eff ort  t o  p erf or m  t he  a p pr o priate  
assess me nts f or t he E n d  of St u d y/ Earl y Ter mi n ati o n visit 
 
 
9. 2. 6. 2  
S u bj e ct Di s c o nti n u ati o n  
Eac h s u bject will be f oll o we d t o t he e n d of st u d y, or u ntil t he s po ns or deci des t o ter mi nate 
t he st u d y, w hic he ver c o mes first. T he o nl y reas o ns a s u bject will n ot be f oll o we d f or all 
sc he d ule d  visits  i ncl u de wit h dra wal  of  c o ns e nt  (see Secti o n 9. 2. 5 ),  c o nti n u o us  
n o n-c o m plia nce wit h pr ot oc ol re q uire me nts, or l oss t o f oll o w- u p (e. g., m o vi n g a wa y fr o m 
st u d y site; u nres p o nsi ve t o atte m pts t o c o ntact t he s u bject). 
T he  i n vesti gat or  ca n  disc o nti n ue  a n y  s u bject,  at  a n y  ti me,  if  me dicall y  necessar y.  
T he  reas o n  f or  t he  s u bject’s  disc o nti n uati o n s h o ul d  be  d oc u me nte d  i n  t he  e C R F. 
T he  i n vesti gat or  s h o ul d  ma ke  e ver y  atte m pt  t o  c o m plete  t he  rec o m me n de d  f oll o w- u p 
assess me nts s pecifie d f or t he last st u d y visit.  
If a n o n-seri o us A E is u nr es ol ve d at t he ti me of t he s u bject’s fi nal st u d y visit, a n eff ort will 
be ma de t o f oll o w  t he s u bject u ntil t he A E is res ol ve d or sta bilize d, t he s u bject is l ost t o 
f oll o w-u p, or s o me ot h er res ol uti o n of t he e v e nt  occ urs . T he i n vesti gat or s h o ul d ma k e 
e ver y atte m pt t o f oll o w all S A Es/ U A D Es t o res ol uti o n. I nf or mati o n o n pre g na nc y a n d t he 
o utc o me f or a n y fe male w h o bec o mes pre g na nt d uri n g t he st u d y will be c ollecte d. 
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9.2.6.3 
Provision of Care for Subjects after Study Discontinuation 
The investigator is responsible for ensuring the adequate and safe medical care of subjects 
during the study. After study discontinuation, the sponsor will follow all applicable local 
regulations and guidelines with regard to a subject’s follow-up care. The investigator will 
ensure that appropriate consideration is given to a subject’s post-study care. 
9.2.7 
Premature Suspension or Termination of the Study 
Should the investigator, sponsor, the FDA, or local regulatory authorities become aware of 
conditions arising during the conduct of this study that may warrant the cessation of the 
study, such action may be taken. Prior to such action, consultation between the sponsor, 
the investigator, and, as appropriate, the FDA and/or local regulatory authorities will occur. 
In the case of a reported vascular embolic event leading to skin necrosis, vision loss, or 
stroke, enrollment and treatment at the investigational site will be suspended and a 
root-cause investigation will be conducted to determine the cause and whether the outcome 
was anticipated (the investigator did not properly follow the treatment instructions) or 
unanticipated (the investigator did properly follow the treatment instructions). 
The investigator and the sponsor will conduct a thorough evaluation of the event. If the 
evaluation reveals the outcome was unanticipated, the entire study will be immediately 
suspended, and no subjects will be enrolled or treated until the event can be properly 
characterized and an appropriate treatment strategy to avoid this unanticipated event can 
be devised. 
Reasons for the premature suspension or termination of the study include, but are not 
limited to: 
• Determination of a potential safety risk to subjects; 
• Inadequate subject enrollment; 
• Decision by the IEC/IRB to suspend or terminate approval/favorable opinion for the 
study; and/or 
• Sponsor decision. 
In the event of a public health emergency, the sponsor will inform all investigators, the 
IEC/IRB, and the relevant regulatory authorities promptly of any planned mitigations to 
protect the safety and well-being of subjects. This can include but is not limited to: putting 
the study recruitment on hold, stopping or postponing further treatments, or changing 
on-site visits to visits by phone or at another clinical site (e.g., if the primary site is closed 
due to quarantine). 
In the event of premature study suspension or termination for safety reasons, the sponsor 
will inform all investigators and relevant regulatory authorities promptly of the study 

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suspension/termination and reason for the action. The investigator will conduct site-closure 
activities in accordance with all applicable sponsor and local/international guidelines and 
regulations. 
9.2.8 
Study Site Discontinuation 
Study participation by individual sites may be discontinued by the sponsor for any of the 
reasons listed in Section 9.2.7. Additional reasons for the premature discontinuation of 
study sites include, but are not limited to: 
• Investigator request; 
• Serious or persistent noncompliance with the protocol, local regulations, and/or GCP; 
• Failure to accrue subjects at an acceptable rate; and/or 
• Ethical issues. 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), it might not be feasible for a study site to continue study participation. In this 
scenario, consideration should be made as to whether the trial site closure would affect the 
safety and well-being of participating subjects. Additionally, consideration should be made 
around impact and maintenance of data validity. 
In the event of study-site discontinuation, the sponsor will provide to the study site written 
notification documenting the reason for discontinuation. The investigator will conduct 
site-closure activities in accordance with all applicable sponsor and local guidelines and 
regulations. 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 5  of 1 1 1  
1 0  S T U D Y D E VI C E A N D T R E A T M E N T O F S U B J E C T S  
1 0. 1  D e s cri pti o n  of St u d y D e vi c e  
1 0. 2  I n stru cti o n s f or U s e a n d A d mi ni str ati o n  
B B L  s h o ul d  be  use d  i n  t he  I O H  treat me nt  re gi o n  acc or di n g  t o  t h e  i nf or mati o n  a n d  
i nstr ucti o ns prese nte d i n Secti o n 1 0. 5 . A d diti o nal i nf or mati o n o n pr o d uct usa ge is  pr o vi de d 
i n t he B B L  I nstr ucti o ns f or Use (I F U) 
 
1 0. 3  M et h o d s of A s si g ni n g S u bj e ct s t o Tr e at m e nt Gr o u p s  
S u bjects w h o c o m plete all scree ni n g assess me nts, meet all eli gi bilit y criteria, a n d are 
acce pt e d  f or  e nr oll me nt  i nt o  t he  st u d y  will  be  assi g ne d  a  ra n d o mizati o n  n u m ber. 
Treat me nt -gr o u p  assi g n me nts  will  be  ma de  base d  o n  t he  ra n d o mizati o n  sc he me   (see 
Secti o n 1 3. 1 ). 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 6  of 1 1 1  
1 0. 5  St u d y T re at m e nt  
All pr ot oc ol -s pecific crit eria f or t he a d mi nistrati o n of st u d y treat me nt m ust be met a n d 
d oc u me nte d pri or t o a d mi nistrati o n of a n y st u d y treat me nt. All de vice a d mi nistrati o n s will 
be  perf or me d  o n -site  b y  t he  treati n g  i n vesti gat or.  All  treati n g  i n vesti gat ors  will  be  
b oar d- certifie d  p h ysicia ns  w h o are  trai ne d  a n d  q ualifie d  i n  a d mi nisteri n g  aest hetic  
treat me nts i n t he facial re gi o n, or m ore s pecifi call y, t he I O Hs. 
S u bjects will n ot be dis pe nse d a n y i n v esti gati o nal material. A n y site or s u bject t hat is 
n o nc o m plia nt wit h 
st u d y-treat me nt pr oce d ures  s pecifie d  i n  t he  pr ot oc ol  ma y  be  
disc o nti n ue d fr o m t he st u d y (see Secti o ns 9. 2. 8  a n d 9. 2. 6. 2 , res pecti vel y). 
 
N O T E: I n t he e v e nt of a p u blic healt h e mer g e nc y, treat me nts ma y be h alte d or p ost p o ne d. 
1 0. 5. 1  
Pl a n n e d T r e at m e nt R e gi m e n 
1 0. 5. 1. 1  
I O H Tr e at m e nt R e gi o n  
B B L  is t o be de p osite d i n t he s u pra peri osteal pla ne. I njecti o n v ol u me will be rec or de d. 
 ill ustrates t he I O H treat me nt re gi o n. T he i nfra or bital treat me nt area is at t he 
j u ncti o n of t he l o wer e yeli d a n d mi dface w here a v ol u me deficit has f or me d. T he area is 
b or dere d b y t he n asal si de wall me diall y, t he te m p oral re gi o n of t he b o n y or bit laterall y, t he 
b ul k of t he l o wer e y eli d s u peri orl y, a n d t he s u peri or as pect of t h e mi dface i nferi orl y. 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 7  of 1 1 1  
1 0. 5. 1. 2  
T r e at m e nt A d mi ni str ati o n Pr o c e d ur e 
Eac h I O H of eac h s u bject will be treate d u ntil t he treati n g i n vesti gat or feels a n o pti mal 
res ult is ac hie v e d, defi ne d as “ o pti mal aest hetic c orrecti o n ” f or t h e i m pla nt i n t hat s u bject; 
h o we ver, treat me nt is n ot t o e xcee d t he ma xi m u m all o wa ble i njecti o n v ol u me a s s p ecifie d 
i n Secti o n 1 0. 5. 1. 2. 6 . Treati n g i n vesti gat ors will be trai ne d o n t he MI H A S  a n d i nstr ucte d 
t hat w he n treati n g s u bjects, t he mi ni mal res ult t o be ac hie v e d per I O H is o pti mal aest hetic 
c orrecti o n  or  at  least  1- p oi nt  i m pr o ve me nt  o n  t he  MI H A S  c o m pare d  t o  baseli ne.  
T he  treati n g  i n vesti gat or  will  be  res p o nsi ble  f or  re vie wi n g  w het her  t he  t hres h ol d  f or 
o pti mal aest hetic c orrecti o n or at least 1 -p oi nt MI H A S i m pr o ve me nt of b ot h I O Hs , as 
assesse d b y t he bli n de d e val uat or 4 w ee k s p ost treat me nt, is met si nce t he bli n de d e val uat or 
will n ot ha ve access t o t he s u bject’s st u d y rec or ds.  If a t o uc h- u p is necessar y, it will o nl y 
be a d mi nistere d if t here are n o me dical c o ntrai n dicati o ns or e xisti n g A Es of c o ncer n , as 
deter mi ne d b y t he tr eati n g i n vesti gat or. 
S u bjects w h o ac hie v e at least 1 -p oi nt i m pr o ve me nt  fr o m baseli ne o n t h e MI H A S  of b ot h 
I O Hs 4 wee ks p ost tr eat me nt  ma y ha v e a t o uc h- u p i njecti o n o n o n e or b ot h I O H(s) t o 
ac hie ve o pti mal  c orrecti o n , at t he discreti o n of t he treati n g i n vesti gat or a n d t he s u bject. 
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 8  of 1 1 1  
A d diti o nall y, I O H tr eat me nts will be a d mi nistere d at a mi ni m u m of 3 0 mi n utes a part. 
Vis ual -f u ncti o n assess m e nts m ust be perf or me d 3 0 mi n utes after treat me nt of eac h I O H 
(see Secti o n 1 1. 2. 2. 2. 1 ). T he c o ntralat eral I O H s h o ul d n ot be treate d u ntil t he vis ual -
fu ncti o n  assess me nts  ar e  perf or me d  o n  t he  treate d  si de,  a n d  n o  cli nicall y  si g nifica nt  
c ha n ges ar e n ote d. A d diti o nall y, reti nal p h ot o gra p hs of b ot h e yes will be ta ke n 3 0 mi n utes 
after t h e last treat me nt is c o m plete. If i njecti n g o nl y o ne I O H d uri n g t he t o uc h -u p a n d/ or 
retreat me nt  visits,  o nl y  t he  I O H si de  bei n g  i njecte d  will  re q uire  vis ual-f u ncti o n 
assess me nts at 3 0 mi n utes after treat me nt.  
T he secti o ns bel o w pr o vi de a d diti o nal a d mi nistrati o n i nstr ucti o ns. 
  
A s s e m bl y of C a n n ul a  a n d N e e dl e  
Asse m bl y of C a n n ul a 
1.  T o  attac h t he ca n n ula t o t he s yri n ge, o pe n t he ca n n ula pac ka gi n g t o e x p os e t he h u b. 
Use o nl y t he ca n n ula pr o vi de d wit h t he cli nical trial s u p pl y. 
2.  Re m o ve t he L uer -l oc k s yri n ge ca p fr o m t he distal e n d of t he s yri n ge pri or t o attac hi n g 
t he ca n n ula 
 
3.  H ol di n g  t he  L uer -l oc k  fitti n g  of  t he  s yri n ge,  t wist  t he  ca n n ula  o nt o  t he  s yri n ge. 
T he  ca n n ula m ust be ti g hte ne d sec urel y t o t he s yri n ge. D o n ot o ver -ti g hte n as t his ma y 
brea k t he ca n n ula a n d/ or disl o d ge t he s yri n ge 
 
C CI
C CI
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 3 9  of 1 1 1  
4.  P ull of f t he ca n n ula g uar d t o e x p ose ca n n ula 
 
5.  Pri me t he ca n n ula wit h B B L . 
6.  If e x cess i m pla nt is o n t he s urface of t he L u er-l o c k fitti n g, it will nee d t o be wi p e d 
clea n wit h sterile ga uze. Sl o wl y p us h t he s yri n ge pl u n ger u ntil t he i m pla nt material 
e x u des fr o m t he e n d of t h e ca n n ul a. If lea k a ge is n ote d at t he L u er -l oc k fitti n g, it ma y 
be necessar y t o r e m o ve t he ca n n ula, clea n t he s urfaces of t h e L u er -l oc k fitti n g, a n d 
reattac h t h e ca n n ul a. I n e xtre me cas es, re pl ace b ot h t he s yri n ge a n d t he ca n n ula. 
Asse m bl y of Nee dle  
Pre pare t he s yri n g es of B B L  injecta ble im pla nt a n d t he i njecti o n nee dle(s) as descri be d 
bel o w: 
1.  T o attac h t he 2 7 G ½” nee dle t o t he s yri n ge, o pe n t he nee dle pac ka gi n g t o e x p ose t he 
nee dle h u b. Use o nl y t he 2 7 G ½” nee dle  pr o vi de d wit h t he cli nical trial pr o d uct.  
Re m o ve t he L uer -s yri n g e ca p fr o m t he distal e n d of t he s yri n ge pri or t o att ac hi n g t he 
nee dle  
 
C CI
C CI
C CI
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 4 0  of 1 1 1  
2.  H ol di n g  t he  L uer -l oc k  fitti n g  of  t he  s yri n ge,  t wist  t he  nee dle  o nt o  t h e  syri n ge. 
T he  nee dle m ust be ti g hte ne d sec urel y t o t he s yri n ge. D o n ot o ver-ti g hte n as t his ma y 
brea k t he n ee dle a n d/ or disl o d ge t he s yri n ge 
 
3.  P ull off t he nee dle g uar d t o e x p ose t he nee dl e
4.  Pri me  t he nee dle wit h B B L  i njecta ble i m pla nt. 
C CI
C CI
C CI
C CI
C CI

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5. If excess implant is on the surface of the Luer-lock fittings, it will need to be wiped 
clean with sterile gauze. Slowly push the syringe plunger until BBL injectable implant 
extrudes from the end of the needle. If leakage is noted at the Luer-lock fitting, it may 
be necessary to remove the needle, clean the surfaces of the Luer-lock fitting, and 
reattach the needle. In extreme cases, replace both the syringe and the needle. 
 
Preparation of the Injection Region 
• Any makeup in the IOH area should be removed. 
• As with all transcutaneous procedures, BBL injection carries a risk of infection and 
should be conducted with aseptic technique. 
• Only topical anesthetic, at the preference of the treating physician, or ice may be 
applied. Any medication or therapy must be recorded in the eCRF. 
 
Depth of Injection and Injection Technique  
10.5.1.2.3.1 
Cannula Technique 
1. The cannula injection technique of BBL with regard to the angle and orientation of 
the bevel, the depth of injection, and the quantity administered may vary. 
Fewer injection points may be needed when a cannula is used rather than a needle. 
Insertion sites will typically be at the malar and zygomatic regions. For cannula 
insertion, a skin puncture should first be made at the desired insertion point using the 
provided introductory needle. The needle will be of slightly larger gauge than the 
cannula. After the introductory needle is withdrawn, the cannula is inserted through 
the skin puncture. Prior to each injection, the treating investigator will aspirate by 
pulling back gently on the plunger to confirm the cannula is not positioned 
intravascularly. Subsequently, a tunneling, fanning, or combination injection 
technique will be used to achieve optimal results. Care must be used to avoid 
intravascular injection regardless of technique used. 
2. In general, when the introductory needle and then cannula are inserted, both will be 
parallel to the skin at an approximate angle of 30° or less. BBL will be placed at the 
junction of the lower eyelid and midface, along the inferior orbital rim in the 
supraperiosteal plane. The injection should be performed with a constant, 
low-to-moderate pressure on the plunger, while slowly and gradually withdrawing the 
cannula. Slight elevation of the skin should be observed without significant blanching 
of the skin. To avoid visible lumps and/or discoloration, avoid injection of BBL 
superficially when removing the cannula. When the injection is complete, the site may 
be gently massaged, if necessary. 

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3. The number of IOH injection locations and volumes (not to exceed the maximum 
allowable volumes, see Section 10.5.1.2.6) are at the discretion of the treating 
investigator until optimal results are achieved. Do not overcorrect. 
Immediately stop the injection if a study subject exhibits any of the following symptoms: 
changes in vision, signs of stroke, blanching of the skin, or unusual pain during or shortly 
after the procedure. Subjects should receive prompt medical attention and possibly 
evaluation by an appropriate healthcare practitioner (i.e., specialist) should an intravascular 
injection occur. 
Each subject must also be informed that, at any time over the study interval, if he/she 
experiences signs or symptoms of an intravascular event, similar to those noted above, or 
symptoms listed on the first page of the eDiary or within the ICF, he/she must seek 
immediate medical attention and notify the study physician immediately. The physician 
must refer the subject to a specialist if additional medical attention is deemed necessary. 
10.5.1.2.3.2 
Needle Technique 
1. The needle injection technique of BBL with regard to the angle and orientation of the 
bevel, the depth of injection, and the quantity administered may vary, as in the cannula 
technique. 
2. Needle injections will be performed at the junction of the lower eyelid and midface, 
along the inferior orbital rim in the supraperiosteal plane. 
3. Prior to each injection, the treating investigator will aspirate by pulling back gently on 
the plunger to confirm the needle is not positioned intravascularly. The injection 
should be performed with a constant low-to-moderate pressure on the plunger, while 
slowly and gradually withdrawing the needle. 
4. Linear threading (fanning) and serial puncture techniques, or a combination thereof, 
will be used to achieve the desired result. Minimizing the number of injection points 
may limit the degree of swelling and bruising. 
5. Slight elevation of the skin should be observed without significant blanching of the 
skin. To avoid visible lumps and/or discoloration, avoid injection of BBL superficially 
when removing the needle. 
6. When the injection is complete, the site may be gently massaged, if necessary. 
Immediately stop the injection if a study subject exhibits any of the following symptoms: 
changes in vision, signs of stroke, blanching of the skin, or unusual pain during or shortly 
after the procedure. Subjects should receive prompt medical attention and possibly 
evaluation by an appropriate healthcare practitioner (i.e., specialist) should an intravascular 
injection occur. 

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Each subject must also be informed that, at any time over the study interval, if he/she 
experiences signs or symptoms of an intravascular event, similar to those noted above, or 
symptoms listed on the first page of the eDiary or within the ICF, he/she must seek 
immediate medical attention and notify the study physician immediately. The physician 
must refer the subject to a specialist if additional medical attention is deemed necessary. 
 
Additional injection information 
• If blanching occurs, the injection should be stopped and the area massaged until it 
returns to a normal color. Blanching may be a sign of a vascular occlusion. If normal 
skin coloring does not return, do not continue with the injection. Treat in accordance 
with the American Society for Dermatologic Surgery guidelines, which include 
possible hyaluronidase injection.[1] 
• Correct to the desired volume effect. Do not overcorrect. The degree and duration of 
the correction depend on the character of the defect treated, the tissue stress at the 
implant site, the depth of the implant in the tissue, and the injection technique. 
Markedly indurated defects may be difficult to correct. 
• Follow national, local, or institutional guidelines for use and disposal of medical sharp 
devices. To help avoid needle or cannula breakage, do not attempt to straighten a bent 
needle or cannula. Discard it and complete the procedure with a replacement needle 
from the clinical supply. Do not recap used needles and cannulas. Recapping by hand 
is a hazardous practice and should be avoided. Discard unshielded needles and cannulas 
in approved sharps containers. 
 
Post-Treatment Care/Pain Management  
• To manage post-injection pain, ice may be applied, as needed. 
• Acetaminophen may be taken if instructed by the treating investigator. Any medication 
or therapy used by the subject must be recorded in the eCRF. 
• The following information should be shared with subjects: 
o Within the first 24 hours, subjects should avoid lower eyelid makeup, strenuous 
exercise, 
extensive 
sun, 
or 
heat 
exposure, 
aspirin 
or 
non-steroidal 
anti-inflammatory drugs, and alcoholic beverages. Exposure to any of the above 
may cause temporary redness, swelling, and/or itching at the injection site. 
o Any and all medications or non-drug therapies used throughout study participation 
should be reported by the subject to site personnel for recording in the eCRF. 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 4 4  of 1 1 1  
 
M a xi m u m I nj e cti o n V ol u m e p er I O H 
T otal ma xi m u m v ol u me f or i nitial  i njecti o n or dela ye d -treat me nt i njecti o n is 1.0 m L per 
I O H; t otal ma xi m u m v ol u me f or t o uc h-u p i njecti o n is  0. 5 m L per I O H . S u bjects ma y 
recei v e  n o  m or e  t ha n  1. 0  m L  per  I O H at  retreat me nt . 
 T otal  v ol u me  
a d mi nistere d per I O H  f or t he st u d y s h o ul d n ot e xcee d 2. 5 m L f or t he treat me nt gr o u ps 
( T N a n d T C) or 1. 5 m L f or t he c o ntr ol/ dela y e d-treat me nt gr o u ps (C D T N a n d C D T C).  
1 0. 6   Pr e vi ou s  a n d C o n c o mit a nt  N o n -dr u g T h er a pi e s   
Pre vi o us  t hera pi es  r ecei ve d  pri or  t o  e nr oll me nt  a n d  c o nc o mita nt  t hera pies  s h o ul d  be  
d oc u me nte d i n t he e C R F . 
Restricti o ns re gar di n g pri or or c o nc o mita nt n o n- dr u g t hera pies are disc uss e d i n det ail i n  
Secti o ns  9. 2. 2  ( E xcl usi o n Criteria) a n d 9. 2. 3  ( R estricti o ns d uri n g t he St u d y). 
1 0. 7  St u d y S u p pli e s a n d P a c k a gi n g  of T r e atm e nt S u p pli e s  
B B L  a n d  st u d y  access ories  ( nee dle,  ca n n ula  p ac k)  will  be  pr o vi de d  b y  t he  s p o ns or.  
T he  s p o ns or will pac ka g e st u d y materials acc or di n g t o a p plica ble re g ul at or y re q uire me nts. 
T he s p o ns or will pr o vi de all perti ne nt la beli n g i nf or mati o n as well as a des cri pti o n of t he 
s pecific de vi ce- p ac ka gi n g c o n diti o ns. 
B B L  is t o be use d e x cl usi vel y f or treat me nt of s u bjects e nr olle d i n t his st u d y a n d will be 
la bele d as f oll o ws: “ C A U TI O N - I n vesti gati o nal De vice. Li mite d b y Fe d eral ( or U nite d 
States) La w t o I n vesti gati o nal Use.” De vice la b els will als o n ote t he ma n ufact urer n a me 
a n d a d dr ess , as well as t he q ua ntit y wit hi n t he p ac ka g e. T he I F U  f or t h e i n vesti gati o nal 
pr o d uct will be  pr o vi de d 
 T he cli nical trial s u p pl y s h o ul d be st ore d i n 
a c o ntr olle d area wit h li mite d access a n d st ore d s e parat el y fr o m a n y c o m mercial s u p plies.  
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The following components are supplied for the injection procedure: 
• BBL box containing one sterile 1-mL prefilled glass syringe of BBL with two 27G ½” 
or 30G ½” needles. 
o More than one BBL box may be used depending on injection volume. 
o Use only the 27G ½” needles provided. 
o If subject is randomized to cannula, these needles should not be used. 
• A peel-off subject label, indicating product, to be placed in the source documents. 
• A separate bulk supply of 27G 40 millimeter (mm) blunt-tipped cannula, with a 25G 
introductory needle, will be provided for the cannula-injection procedure. 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), considerations may be made to supply study sites with sufficient study 
supplies to avoid interruptions to the supply chain for the investigational product during 
the outbreak. 
10.8 Receipt, Storage, Dispensing, and Return/Disposal 
Upon receipt, site personnel will verify the contents of all study supplies received and 
promptly notify the appropriate contacts of any discrepancies or damages. The investigator 
is responsible for ensuring an accurate record of inventory is maintained. The investigator 
will keep a current record of the study-product delivery to the study site, inventory, and 
dispensing, and this record will be made available to the sponsor upon request. Study sites 
will be queried about any discrepancies. 
All study devices must be stored in a secure, environmentally controlled, monitored area, 
in accordance with the labeled storage conditions. 
Only authorized study personnel may supply, dispense, and/or administer study treatment, 
and only subjects enrolled in the study may receive study treatment. The investigator is 
responsible for maintaining a current, accurate record of all study-treatment dispensation. 
Any used syringes of investigational device and needles or cannulas should be discarded 
per the appropriate handling and disposal procedures at the site. Any unopened product, 
needles, cannulas, and/or outer packaging of used kits should be retained so the monitor 
can perform device-accountability procedures. 
At the end of the study and after verification of study device accountability, it is the 
investigator’s responsibility to return all unused study supplies, as directed by the sponsor. 
Appropriate records of return must be maintained for accountability purposes. 

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All study-accountability procedures must be completed before the study is considered 
complete. 
10.9 Device Accountability Procedures 
The sponsor will provide the investigator with all necessary study supplies. Accountability 
for study supplies at the study site is the responsibility of the investigator. 
Access to the IMD will be controlled, and IMD will be used only in the clinical 
investigation and according to the clinical study protocol. The sponsor will keep records to 
document the physical location of all IMDs from shipment to the investigation sites until 
return or disposal. The principal investigator or an authorized designee will keep records 
documenting the receipt, use, return, and disposal of the IMDs, which will include the 
following: 
• The date of receipt and quantity of units received. 
• Identification of each IMD (batch number/serial number or unique code). 
• The expiration date (if applicable). 
• The names of all persons who received, used, or disposed of each device. 
• The date(s) of use. 
• Unique subject identification number. 
• Date and quantity of units returned. 
• The date of return of unused, expired, or malfunctioning IMDs (if applicable). 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), considerations may be made to perform study-accountability procedures 
remotely and return of unused supplies may be delayed until return procedures can be 
safely performed by site personnel. 
10.10 Treatment Compliance 
Treatment is administered by the treating investigator and thus assessment of compliance 
is unnecessary. Potential deviations from the defined study-treatment administration will 
be reported as protocol deviations. 
10.11 Duration of Study 
The planned duration of participation for individual subjects from baseline to the end of 
the study is 76 weeks (± 14 days). In addition, subjects will also undergo a screening period 
up to 10 days and at least 3 days prior to the baseline visit. 

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In the event of a public health emergency the study might be halted, recruitment 
interrupted, and/or study processes and flow might be modified, impacting to the study 
duration and/or visit schedule depending on the study status at the time of the event. 
Mitigations may include, but are not limited to, extending visit windows, performing visits 
by phone or video, and/or performing effectiveness assessments remotely. 
 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 4 8  of 1 1 1  
1 1  S T U D Y P R O C E D U R E S  
1 1. 1  Vi sit S c h e d ul e  
T o deter mi ne s u bject eli gi bilit y f or st u d y partici pati o n, a scree ni n g e val uati o n  m ust be 
c om plete d fr o m − 1 0 t o − 3 da ys bef ore baseli ne.  Eli gi ble s u bjects will be ra n d o mize d at 
t he scree ni n g visit. 
After scr ee ni n g e val u ati o n, eac h s u bject ra n d o mize d t o treat me nt will ha ve bet wee n 1 0 a n d 
1 4 visits , de pe n di n g o n w het her he/s h e  recei ves a t o uc h- u p a n d/ or retreat me nt i njecti o n. 
S u bjects ra n d o mize d t o c o ntr ol will re mai n u ntreate d u ntil Wee k 8, w he n t he pri mar y  
effecti ve ness   e n d p oi nt is e val uate d. U p o n c o m pl eti o n  of all effecti ve ness assess me nts , 
c o ntr ol s u bjects will be treate d wit h B B L  (i.e., will recei v e dela y e d treat me nt). After 
scree ni n g  e val u ati o n,  eac h  su bject  i n  t he  c o ntr ol/dela ye d -treat me nt gr o u p  will  ha ve  
bet wee n 8 a n d 1 0 visits, de pe n di n g o n w het her he/s he recei ves a t o uc h - u p i njecti o n. 
T he pri mar y e n d p oi nt visit will occ ur at Wee k  8 ( +  7 d a ys)  p ost last i njecti o n (i.e., i nitial 
i njecti o n or t o uc h-u p, if a p plica ble)  f or t he treat m e nt gr o u p a n d at Wee k 8 ( + 7 da ys) after 
scree ni n g f or t he c o ntr ol/ dela ye d-treat me nt gr o u p. 
F or s u bjects i n t he treat me nt gr o u p, t he fi nal visit will occ ur 7 2 wee ks ( ±  1 4 da ys) p ost last 
i njecti o n (i nitial or t o uc h- u p, if a p plica ble) or 2 4 wee ks p ost retreat me nt (if a p plica ble).  
F or s u bjects i n t he c o ntr ol/ dela ye d -treat me nt, t he fi nal visit will occ ur 4 8 w ee ks ( ± 1 4 d a ys) 
p ost last i njecti o n (i nitial or t o uc h- u p, if a p plica ble). 
1 1. 2  St u d y A s s e s s m e nt s a n d D efi niti o n s  
1 1. 2. 1  
Eff e cti v e n e s s A s s e s s m e nt s  
Refer  t o  t he  res pecti ve  e n d p oi nts  (see  Secti o n 7. 2. 1 )  
 
 f or a d diti o nal i nf or mati o n i ncl u di n g t he ti min g of effecti ve n ess 
assess me nts.  
1 1. 2. 1. 1  
M er z I nfr a or bit al H oll o w A s s e s s m e nt S c al e ( MI H A S)  
T he MI H A S w as desi g ne d t o assess t he i nfra or bit al h oll o w t hat res ults fr o m v ol u me l oss. 
Eac h gr a de of t h e MI H A S is disti nct ; Gra de 0 is a nc h ore d t o de pi ct n o ne t o mi ni mal si g ns 
of h oll o wi n g , a n d Gra d e 4 is a nc h ore d t o de pi ct e xtre me si g ns of h oll o wi n g 
 
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CLINICAL STUDY PROTOCOL 
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CONFIDENTIAL AND PROPRIETARY 
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In the current study, the MIHAS will be used to detect clinically relevant, aesthetic changes 
as a result of volume correction in the IOH area. 
For each of the five severity grades presented on the scale, three reference subjects are 
displayed. For each subject, a frontal view is presented to indicate specific characteristics 
of the IOH region. The left and right IOH of each subject is assessed independently on the 
MIHAS within this study. 
During the baseline and subsequent study visits, subjects will be evaluated live on the 
MIHAS by a trained evaluator (i.e., a qualified healthcare practitioner delegated by the 
treating investigator); this evaluator is blinded to the subject’s treatment assignment and 
will perform the respective assessment independently from any study staff. Prior to study 
enrollment, at least one blinded evaluator at each site will be trained and qualified by the 
study sponsor to perform scale-grading assessments. Training will consist of an 
instructional session, followed by a qualification where blinded-evaluator trainees will 
score two sets of photographs, representing a variety of different MIHAS grades, at least 
two weeks apart. The purpose of this assessment is to obtain intra- and inter-evaluator 
reliability qualification analyses prior to starting the study at their respective site 
(i.e., weighted Kappa/ICC analyses). Any blinded evaluator who does not successfully 
achieve an intra- and inter-rater (pair-wise against other raters) reliability point estimate 
value of ≥ 0.70 will be retrained and requalified up to two times. If evaluator retention 
(e.g., change in personnel) becomes an issue during the study, new blinded evaluators must 
be trained by the sponsor, and respective qualification analyses must be performed. 
Qualification and training of blinded evaluators will be documented. At each study site, all 
efforts should be made to plan for and maintain the same blinded evaluator for all 
assessments throughout the study. To account for illness or unplanned absence of the 
blinded evaluator, it is recommended to have at least one back-up blinded evaluator trained 
and qualified per site. Evaluators will be re-trained on the MIHAS at regular intervals 
(approximately every 3 months at a minimum). 
The treating investigator will also attend a MIHAS-instructional session to ensure 
understanding of the subject-eligibility criteria of right and left IOH volume deficit with a 
rating of 2 or 3 (moderate or severe) at study entry. 
Additionally, three blinded IPRs will assess subject photographs using the MIHAS.  
Note: For subjects randomized to treatment, the photographs assessed will be from 
Screening or Day 1 (Visit V1a) and 8 weeks post last injection (Visit V3). For subjects 
randomized to the control/delayed-treatment group, the photographs assessed will be from 
Screening, Day 1 (8 weeks from the screening visit, Visit C1a) and 8 weeks post last 
injection (Visit C3).  

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 0  of 1 1 1  
T hese b oar d- certifie d I P Rs, w h o are n ot part of t he st u d y sites, will be q ualifie d usi n g t he 
met h o d ol o g y  descri be d  f or  bli n de d  e v al uat ors  a b o ve.  F urt her  det ails  re gar di n g  
p h ot o gra p hs ar e pr o vi de d i n Secti o n 1 1. 2. 1. 2 . 
1 1. 2. 1. 2  
P h ot o gr a p h s  
F or  s u bjects  ra n d o mize d  t o  treat me nt,  sta n dar dize d  p h ot o gra p hs  will  be  ta ke n  at  t he  
scree ni ng  visit  ( pri or  t o  treat me nt)  a n d  at  m ulti ple  i nter vals  t hr o u g h o ut  t he  st u d y.  
P h ot o gra p hs  c ollecte d  at  scree ni n g  will be  re vie we d  a n d  acce pte d  b y  t he  ce ntral  
p h ot o gra p h y ve n d or pri or t o  treat me nt- gr o u p s u bjects prese nti n g f or treat me nt ( Da y 1). If a 
s u bject’s scree ni n g p h ot o gra p hs are dee m e d u ns atisfact or y b y t he ce ntral p h ot o gra p h y 
ve n d or, p h ot o gra p hs will  be ret a ke n at Da y 1  ( pri or t o treat me nt). If n o res h o ot is nee de d, 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 1  of 1 1 1  
t he scree ni n g p h ot o gra p h will defa ult t o t he baseli ne p h ot o gra p h a n d will be use d f or 
refere nce t hr o u g h o ut t he st u d y. Si nce baseli ne p h ot o gra p hs are of critical i m p orta nce as a  
refere nce meas ure t hr o u g h o ut t he st u d y, it is esse ntial t hat all st u d y-s pecific p h ot o gra p h y 
pr oce d ur es, as des cri be d i n a se parate user m a n ual, are f oll o w e d . 
F or s u bjects ra n d o mize d t o c o ntr ol/dela ye d -treat m e nt, i n a d diti o n t o t he scree ni n g/ baseli ne 
p h ot o gra p hs, sta n dar dize d p h ot o gra p hs will b e t a ke n at t he d ela ye d treat me nt baseli ne 
bef ore tr eat me nt is a d mi nistere d  a n d at m ulti ple i nter vals t hr o u g h o ut t he st u d y.  
E ver y eff ort s h o ul d be ma de t o ha v e t he sa m e st u d y pers o n nel ta k e p h ot o gra p hs t hr o u g h o ut 
t he st u d y; f urt her m ore, t h e sa me p h ot o gra p h y c o n diti o ns/e n vir o n me nt m ust be mai ntai ne d 
at e ver y visit. Scree ni n g p h ot o gra p hs a n d/ or refere nce ti me p oi nt p h ot o gra p hs will be use d 
f or c o m paris o n f or t he tr eati n g i n vesti gat or a n d s u bject G AI S assess me nts c o n d ucte d at 
m ulti ple ti me p oi nts d uri n g t he st u d y (see Secti o ns  1 1. 2. 1. 3  a n d 1 1. 2. 1. 4  f or refere nce t o 
t he  G AI S  assess me nts) as  well  as  f or  t he  I P Rs  assess me nt  (see  Secti o n 1 1. 2. 1. 1 ). 
P h ot o gra p h y pr oce d ur es a n d s pecificati o ns, i ncl u di n g s u bject p ositi o ni n g  a n d ca mera a n d 
li g hti n g set- u p req uire me nts, will be descri be d i n a se parat e user ma n u al.  
1 1. 2. 1. 3  
Tr e ati n g I n v e sti g at or Gl o b al A e st h eti c I m pr o v e m e nt S c al e ( G AI S)  
T he treati n g i n v esti gat or will use t he 7 - p oi nt G AI S 
 t o assess gl o bal aest hetic 
i m pr o ve me nt of t he I O Hs b y ma ki n g c o m paris o ns bet wee n p h ot o gra p hs t a ke n at vari o us 
p ost- treat me nt  ti me  p oi nts  a n d  pre -treat me nt p h ot o gra p hs  ( see Secti o n  1 1. 2. 1. 2 ). T he  
res pecti ve  p ost-tr eat me nt  p h ot o gra p h  will  be  dis pla ye d  si de- b y-si de  wit h  t he  baseli ne 
p h ot o gra p h f or t he treati n g i n vesti gat or t o assess aest hetic  i m pr o ve me nt. F or s u bjects 
recei vi n g  retr eat me nt,  t he  p ost -retreat me nt  p h ot o gra p h  will  be  c o m pare d  t o  b ot h  t he  
baseli ne  p h ot o gra p h a n d t he 4 8- wee k  p h ot o gra p h (t a ke n pri or t o retreat me nt). All treati n g -
i n vesti gat or G AI S rati n gs s h o ul d be base d o n t he c urre nt c os metic res ult f or b ot h I O H s. 
I n v esti gat ors will rate b ot h I O Hs c o nc urre ntl y a n d will be as ke d t he f oll o wi n g q uesti o n: 
“Please r ate t he o v er all i m pressi o n of p ost -treat me nt aest hetic c ha n g e s pecific t o t he I O Hs 
o n p h ot o gra p hs ta ke n d uri n g t he visit c o m pare d wit h t he refere nce p h ot o gra p h. Select o ne 
rati n g t hat best a p plies.” 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 2  of 1 1 1  
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 3  of 1 1 1  
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 4  of 1 1 1  
1 1. 2. 1. 6  
P ai n Vi s u al A n al o g u e S c al e ( P ai n V A S)  
Pai n will be as sesse d usi n g a V A S.[ 2-4]  T his V A S i ncl u des 2 1 -n u m bere d circles at 0. 5 c m  
i ncre me nts, s pa n ni n g 1 0 c m t otal, a n d is a nc h ore d b y w or d descri pt ors 
 T he  
o verall  le vel of pai n will be e val uate d 5 mi n utes p ost treat me nt ta ki n g i nt o c o nsi derati o n 
b ot h I O Hs. 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 5  of 1 1 1  
S u bjects will be prese nte d wit h t he pai n V A S a n d as ke d t o circle t he o ne ( 1) n u m ber t hat 
best descri bes t heir p ai n le vel p ost treat me nt.  
1 1. 2. 1. 7  
Li k eli h o o d of R etr e at m e nt S ur v e y  
At t he en d of st u d y/earl y ter mi nati o n visit, all treate d s u bjects will be as ke d: “ H o w li kel y 
w o ul d y o u be t o h a ve f ut ure Bel oter o Bala nce wit h Li d ocai ne treat me nts i n t he i nfra or bital 
h oll o w ( area u n der t he e y es) ? Please tic k o n e b o x bel o w ” 
If t he s u bject res p o n ds “s o me w hat u nli kel y”, “ u nli kel y”, “e xtre mel y u nli kel y”, he/s he will 
be as ke d f or a d diti o nal e x pla nati o n as t o w h y he/s he is n ot li kel y t o ha ve f ut ure Bel oter o 
Bala nce wit h Li d ocai ne treat me nts  i n t he I O H area. 
1 1. 2. 2  
S af et y A s s e s s m e nt s  
Sta n dar d saf et y assess me nts, i ncl u di n g d oc u me ntati o n of A Es a n d S A Es re p orte d b y t he 
i n vesti gat or t hr o u g h o ut t he st u d y, will be e val uate d. Su bjects will be f oll o we d f or u p u ntil 
t heir e n d of st u d y visit. 
Refer t o t he res pecti ve e n d p oi nts (see Secti o n 7. 2. 2 ) a n d t he Sc he d ule of E ve nts  
 
 f or a d diti o nal i nf or mati o n o n t he safet y assess m e nts. 
F or safet y defi niti o ns a n d a d diti o nal i nf or mati o n , please see Secti o n 1 2 . 
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11.2.2.1 
Secondary Safety Assessments 
 
Adverse Events (AEs) 
All AEs reported by investigators or other study staff after the time of informed consent 
through the last study follow-up visit will be recorded. Events will be recorded regardless 
of causality. The period of observation for an AE extends from when the ICF is signed 
until the subject’s last study visit. Additional information is provided in Section 12.1. 
Adverse events will be assessed at all on-site study visits and during follow-up telephone 
calls. 
Any medical occurrence from the time the ICF is signed is an AE and must be documented 
in the subject’s file and on the AE eCRF. Any AE observed will be fully investigated, 
documented, and followed until the event is either resolved or adequately explained, until 
the end of study/early termination visit. 
In this study, any AE of visual disturbance will be reported (see Section 11.2.2.2.1). The 
investigator needs to report any AE of visual disturbance within 24 hours to the sponsor 
using the Report of Visual Disturbances Form (see Section 12.7). 
 
Serious Adverse Events (SAEs) 
All SAEs reported by investigators or other study staff after the time of informed consent 
through the last study follow-up visit will be recorded. Events will be recorded regardless 
of causality. Any SAE observed will be fully investigated, documented, and followed until 
the SAE is resolved or a plausible explanation is available. Serious AEs occurring after the 
end of the observational period need to be reported if the investigator considers the event 
to be related to the IMD. Additional information is provided in Section 12.2. Serious AEs 
will be assessed throughout the study, including on-site study visits and during follow-up 
telephone calls. 
11.2.2.2 
Other Safety Assessments 
 
Visual-Function Assessments 
Although the incidence of AEs/SAEs associated with retinal artery occlusion is very low, 
treated subjects will undergo visual examinations to potentially identify ophthalmic signs 
and/or symptoms that may represent ophthalmic-artery occlusion. 
Visual-function assessments will include a visual-acuity test (using a Snellen chart), a 
confrontation-visual field test, and an ocular-motility examination. These assessments will 
be completed at screening, pre-treatment, post-initial injection, pre- and post-treatment for 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 7  of 1 1 1  
t he t o uc h-u p a n d retr eat me nt i njecti o ns  (if a p plica ble), pre- a n d p ost -treat me nt f or the 
dela ye d -tr eat me nt i njecti o ns, a n d at all f oll o w-u p visits  
 T he af ore m e nti o ne d 
vis ual safet y  assess me nts  ca n  be  perf or me d  b y  t he  treati n g  i n vesti gat or  or  a  trai ne d  
dele gate.  T he s u bject’s  visi o n  will  be assesse d  weari n g  t h e sa me  per mitte d s pectacle 
c orrecti o n a n d i n t he sa me e xa m r o o m t o hel p t o c o ntr ol f or differe n ces i n r o o m li g hti n g 
a n d ot her c o n diti o ns. 
I n  a d diti o n,  u n dilate d reti nal  p h ot o gra p hs  will  be  ta ke n  at  t he  scree ni n g  visit  
( pre-tr eat me nt), aft er i nitial treat me nt, after t o uc h- u p  i njecti o n, if a p plica ble, a n d at t he 
o pti o nal retreat me nt visit bef ore a n d after i njecti o n  
 P h ot o gra p hs will be 
ca pt ure d usi n g n o n -m y driatic reti nal ca meras a n d will be rea d b y a ce ntral o p ht hal mic 
i ma gi n g ce nter ( ce ntr al r ea der). 
A n y a b n or malit y i de ntifie d d uri n g t he vis ual -f u ncti o n assess me nts at scree ni n g a n d/ or 
bef ore i nitial i njecti o n s h o ul d be d oc u me nte d as me dical hist or y. F oll o wi n g t he scree ni n g 
visit, if t he ce ntral rea der detects a cli nicall y rele va nt vis ual pat h ol o g y t hat ma y p ote ntiall y 
i nterfer e wit h st u d y res ults or p ote ntiall y e n h a nce t he safet y c o n cer ns of a s u bject as a res ult 
of treat me nt, t he s u bject will nee d t o be e val uate d f or w het her he/s he meets o ne or m ore 
e xcl usi o n criteria a n d s h o ul d n ot be treate d. 
Vis ual -f u ncti o n assess m e nts will be perf or me d 3 0 mi n utes after treat me nt of eac h I O H. 
T he  c o ntralateral I O H s h o ul d n ot  be treate d u ntil  t he vis ual-f u ncti o n  assess me nts  are  
perf or me d o n t he tr eate d si de, a n d n o cli nicall y  si g nifica nt c ha n g es are n ot e d. A d diti o nall y , 
reti nal p h ot o gra p hs of b ot h e yes will be ta ke n 3 0 mi n utes after c o m pleti o n of treat me nt of  
b ot h I O Hs. 
A n a b n or malit y is defi n e d as a n y p ara m eter t hat is cli nicall y si g nifica nt i n n at ure or a dr o p -
i n visi o n b y o ne li ne or m ore. If a n y s u c h a b n or malit y is detecte d o n t he vis ual-f u ncti o n 
assess me nts at a treat me nt visit  (i nitial i njecti o n, t o uc h-u p, retreat me nt) , t he s u bject will be 
referre d t o a n o p ht hal m ol o gist f or f urt her e v al uati o n. I n a d diti o n, t he a b n or malit y will be 
d oc u me nte d as a n A E. 
W he n t he s u bject r et ur ns f or t he 2 -w ee k safet y f oll o w -u p visit a n d all s u bse q ue nt   n o n-
treat me nt visits, t he vis ual -f u ncti o n ass ess me nts will be re peate d, a n d t he s u bject will be 
assesse d f or a n y c ha n g es t hat c o ul d i n dicate a s afet y c o ncer n. A n a b n or m alit y is defi ne d 
as a n y para meter t hat is cli nicall y si g nifica nt i n nat ure or a dr o p -i n visi o n b y o ne li ne or 
m ore. If  a n y s uc h  a b n or mality  is  detecte d  o n  t he  vis ual -f u ncti o n  assess me nts,  reti nal  
p h ot o gra p hs will be ta ke n a n d re vie w e d b y t he ce ntral rea der.  I n a d diti o n, t he a b n or malit y 
will be re p orte d as a n A E . 
S u bjects will n ot be eli gi ble f or a t o uc h- u p i njecti o n or retreat me nt (if a p plica ble), if: 
•  A b n or malities  i n vis ual-f u ncti o n assess me nts visi o n c ha n ge are d o c u me nte d b y t he 
treati n g i n vesti gat or t o be relate d t o st u d y treat me nt; 
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Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 5 8  of 1 1 1  
•  A n y c o nstricti o n o n vis ual fiel d testi n g is o bser ve d (treati n g i n vesti gat or s h o ul d refer 
t he s u bject t o a n o p ht hal m ol o gist or reti nal s pecialist ); or 
•  A n y ne w s y m pt o matic c ha n ges i n oc ular m otilit y are det er mi ne d b y t he treati n g 
i n vesti gat or t o be cli nicall y rele va nt a n d/ or relate d t o st u d y treat me nt. 
I n t his st u d y, a n y A E  of vis ual dist ur ba nce (i ncl u di n g, b ut n ot li mite d t o, a n y l oss of vi si o n, 
bl urr y visi o n, d o u ble visi o n, pai n i n or ar o u n d e ye [ot her t ha n t y pical i njecti o n -i n d uce d 
pai n ], bli n d s p ot or s ha d o w i n t he vis ual fiel d, tr o u ble m o vi n g e yes, etc.) will be re p orte d. 
T he i n vesti gat or will be i nstr ucte d t o re p ort a n y A E of vis ual dist ur ba nce wit hi n 2 4 h o urs 
t o  t he  s p o ns or  usi n g t he  Re p ort  of  Vis ual  Dist ur ba nces  F or m (see Secti o n 1 2. 7 ). 
T he  i nci de nt will t he n be re p orte d t o F D A  wit hi n 1 0 b usi ness  da ys of recei pt b y t he 
s p o ns or. T hese re p orts will be ge nerate d b y t he s p o ns or or d esi g nee a n d will i ncl u de t he 
de pt h of i njecti o n,  i njecti o n v ol u me, s y m pt o ms o bser ve d, ti me t o o ns et a n d res ol uti o n, a n d 
a n y i nter ve nti o ns i m ple me nte d. 
 s u m marizes t h e sc he d ule f or vis ual assess me nts. 
1 1. 2. 2. 2. 1. 1  
Vi s u al A c uit y  
Vis ual ac uit y will be deter mi ne d usi n g t he S nelle n c hart. Eac h site will be e q ui p pe d wit h a 
S nelle n c hart. T he la ne a n d dista nce  ( 1 0 feet) fr o m t he c hart will be c o nfir me d b y t he 
m o nit or pri or t o be gi n ni n g t he scree ni n g acti vities at t h e site. 
T he site will f oll o w sta n dar d directi o ns f or usi n g t he S nelle n c hart i n deter mi ni n g vis ual 
ac uit y. T he s u bject will be as ke d t o c o ver o ne e ye ( if t he s u bject wears glasses/c o ntacts f or 
dista nce visi o n he/s he will be as ke d t o kee p t he m o n/i n). T he e xa mi ner will p oi nt t o eac h 
li ne as t he s u bject rea ds t he letters al o u d. T he s mallest li ne w here t he s u bject i de ntifie d t he 
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CONFIDENTIAL AND PROPRIETARY 
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majority of letters correctly will be recorded. Visual acuity is expressed as a fraction. The 
visual acuity will be recorded per eye. 
11.2.2.2.1.2 
Confrontation-Visual Field Test 
The confrontation-visual field test will measure how sensitive the vision is in different parts 
of the visual axis. A confrontation visual field test can determine if the subject has blind 
spots in his/her vision, and if so, where the blinded spots are. The examination should be 
performed without the subject wearing glasses (note: contacts are permitted). To measure 
the visual field, the examiner will use the standard finger test according to the American 
Academy of Ophthalmology. 
The subject will be asked to look directly at an object in front while covering one eye. 
The investigator or delegate will hold up different numbers of fingers in areas of the 
subject’s peripheral-vision field and ask how many fingers he/she sees while looking at the 
target in front. 
11.2.2.2.1.3 
Ocular-Motility Exam 
The examiner should determine if the subject’s range of ocular movement is intact in each 
direction of gaze. The examination should be performed without the subject wearing 
glasses (note: contacts are permitted). To begin, the subject should be asked to look at a 
distant object while his/her head is facing straight ahead. The subject’s head should not be 
tilted up, down or to the side. Symmetry between the eyes should be noted in primary 
position. The subject should then be asked to follow the examiner’s finger without the 
subject moving his/her head. The examiner should use his/her index finger on either the 
right or left hand for guiding the direction of eye movement. The investigator should move 
the index finger to the left, right, up and right, up and left, down and left, down and right, 
straight up and straight down. The subject should be asked to voice if he/she experiences 
double vision in any position of gaze and/or in any of the fields. The examiner should look 
for and document any asymmetry in ocular motility or abnormal ocular motility. 
11.2.2.2.1.4 
Undilated Central Retinal Exam Using a Non-mydriatic 
Retinal Camera 
In this procedure, the treating investigator or delegate will take pictures of the undilated 
central retina and blood vessels using a non-mydriatic retinal camera system. Note: pictures 
must be taken without the subject wearing glasses or contacts. Subsequently, images will 
be uploaded and remotely evaluated by a specialist at a central ophthalmic imaging center. 
The investigational site will receive an assessment report from the central ophthalmic 
imaging center within 24 hours. If any retinal findings are noted, the site will contact the 
subject and the site-identified ophthalmology practice to arrange an immediate evaluation. 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 6 0  of 1 1 1  
1 1. 2. 2. 2. 1. 5  
Dir e cti o n s f or I ntr a v a s c ul ar I nj e cti o n or E m b oli c E v e nt  
Eac h site will i de ntif y a l ocal o p ht hal m ol o g y practice t hat is  e q ui p p e d a n d q ual ifie d t o 
a d dress a n y vis ual c ha n g es a n d a p ote ntial reti nal arter y o ccl usi o n t hat ma y o cc ur as a res ult 
of i njecti o n (i. e., cli nicall y si g nifica nt c ha n g es i n visi o n, s uc h as bli n d n ess, bl urri ness, 
d o u ble visi o n, pai n i n or ar o u n d t he e ye [ot her t ha n t y pica l i njecti o n-i n d uce d pai n], bli n d 
s p ots, or restricti o n of e y e m otilit y). 
I n t he e ve nt of i ntra vas c ular i njecti o n or e m b olic e ve nt, t he treati n g p h ysicia n will pr o vi de 
pr o m pt me dical atte nti o n a n d f oll o w t he pr o p er pr ot oc ol i n acc or d a nce wit h t he A merica n 
S ociet y  f or  Der mat ol o gic  S ur ger y  g ui deli nes. [ 1] If  t he  i njecti o n  is  i n  pr o gress,  best  
practices s h o ul d be use d t o st o p t he i njecti o n. T he treati n g p h ysicia n s h o ul d c o nsi der t he 
f oll o wi n g: a n i m me diate referral t o t he site-i de ntifie d o p ht hal m ol o g y practice, i njecti o n of 
h yal ur o ni dase (if a p plica ble) i n t he a nat o mic area of treat me nt a n d/ or retr o b ul bar, a n d 
c o nsi derati o n of acti ve r e d ucti o n of i ntra oc ular press ure. T he i n vesti gat or s h o ul d treat i n 
acc or d a nce wit h t he A merica n S ociet y f or Der m at ol o gic S ur ger y g ui deli nes. [ 1] 
 
7 2 -h o ur P o st Tr e at m e nt  P h o n e C all  
All s u bjects will r ecei ve a p ost- treat me nt p h o ne call 7 2 h o urs ( + 1 d a y) after t he i nitial 
treat me nt, after t he t o uc h- u p treat me nt, if a p plica ble, a n d/ or aft er o pti o nal retreat me nt. 
D uri n g t his p h o ne call, st u d y pers o n nel will disc uss a n d rec or d a n y c ha n ges i n c o nc o mita nt 
me dicati o ns/ pr oce d ur es  a n d  c o nfir m  t hat  t h e  s u bject  re mai ns  c o m plia nt  wit h  a n y  
a p plica ble st u d y r estricti o ns. St u d y pers o n nel  will  als o disc uss t he c o m pleti o n of t he 
s u bject e Diar y a n d re mi n d t he s u bject h o w t o utilize t he e Diar y f or dail y e ntries. If t here 
are a n y safet y c o ncer ns t hat w o ul d necessitate a n u nsc he d ule d visit t o t he site, t his visit 
s h o ul d be sc he d ule d d uri n g t he p h o ne call. 
I n a d diti o n, eac h s u bject will be as k e d if he/s he e x perie nces a n y ne w or u n us ual s y m pt o ms 
relate d t o a p ote ntial vas c ular occl usi o n (e. g., si g ns of a str o k e, c h a n ges i n visi o n, tiss ue 
necr osis) as n ote d i n t he St u d y I nf or mati o n G ui de f or S u bjects. If a n y ot h er s uc h s y m pt o ms 
relate d t o a p ote ntial v asc ular o ccl usi o n are re p orte d b y t he s u bject, h e/s he s h o ul d be 
assesse d, a n d r eferre d f or i m me diate me dical treat me nt as dee me d n ecessar y per best 
me dical practices. If a n y c ha n ge i n visi o n is re p orte d d uri n g t he 7 2-h o ur f oll o w -u p p h o ne 
call, t he s u bject ma y b e r eferre d i m me diatel y t o t h e site -i de ntifie d o p ht hal m ol o g y practice 
or a l ocal e mer ge nc y r o o m (if t he o p ht hal m ol o g y practice ca n n ot be reac he d or is n ot 
a vaila ble) f or f urt h er e v al uati o n. 
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 6 1  of 1 1 1  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 6 2  of 1 1 1  
1 1. 2. 3  
Ot h er A s s e s s m e nt s  
Data f or ot h er ass ess me nts will be c ollecte d  as f oll o ws: 
•  De m o gra p hics a n d ot her baseli ne c haracteristics ; 
•  Uri ne pre g n a nc y tests ( o nl y if fe male s u bject is of c hil d beari n g p ote ntial); 
•  I njecti o n  v ol u me  at  all  i njecti o n  visits  (i.e.,  i nitial  i njecti o n, dela ye d -treat me nt 
i njecti o n, t o uc h- u p, if a p plica ble, a n d o pti o nal retreat me nt, if a p plica ble); 
•  I njecti o n tec h ni q ue, l ocati o n, n u m ber of i njecti o n p oi nts, a n d i njecti o n pla ne; 
•  Me dical hist or y/c o nc o mita nt diseases; a n d  
•  Pre vi o us a n d c o nc o mita nt me dicati o ns a n d n o n- dr u g treat me nts. 
 
1 1. 3  M o difi c ati o n s t o St u d y Pr o c e d ur e s D uri n g a P a n d e mi c  
I n t h e e ve nt of a pa n d e mic disease o ut brea k, t he st u d y c o n d uct ma y be affecte d. O n-site 
visits ma y n ot be p ossi ble d ue t o q uara nti nes, site cl os ures, tr a v el li mitati o ns, i nterr u pti o ns 
t o t he s u p pl y c hai n f or t he i n vesti gati o nal pr o d uct, or ot her c o nsi derati o ns. If site pers o n nel 
or trial s u bjects b ec o me i nfecte d  wit h S A R S - C o V-2 (t he vir us t h at ca us es t h e ill ness k n o w n 
as C O VI D - 1 9), visits s h o ul d be c o n d ucte d via p h o ne or virt uall y  t o c ollect s u bject safet y 
a n d eff ecti ve n ess data  (if p ossi ble) re m otel y. 
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The primary goal is to ensure the safety and well-being of subjects while efforts are made 
to ensure data integrity. Visit windows may be adjusted as follows: 
• Prolong screening period to − 28 to − 3 days. In the event that quarantines, site closures, 
travel limitations will not allow subject on-site randomization within this time period, 
re-screening of subjects will be allowed based on easing of local and/or national 
restrictions. 
• Expand the ± 7 day visit windows to ± 14 days. 
• Expand the ± 14 day visit windows to ± 28 days. 
Effectiveness assessments (i.e., GAIS assessments and FACE-Q) may be performed 
remotely, if feasible. 
Forms for effectiveness assessments will be provided to subjects electronically or via mail 
and will be completed by subjects at home. Subjects will return the initialed and dated 
forms back to the study site via mail or at the next possible visit. 
Visual safety assessments cannot be conducted at post-treatment follow-up visits remotely. 
If subjects experience any changes in vision, they will be instructed to immediately contact 
the site-identified ophthalmology practice prior to contacting the site investigator. If a 
subject is unable to contact the site-identified ophthalmology practice, the subject should 
be instructed to either call 911 or visit a local emergency room immediately. 

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12 SAFETY DEFINITIONS AND REPORTING REQUIREMENTS 
12.1 Definition of an Adverse Event (AE) 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical sign (including abnormal laboratory findings) in subjects, users, or other persons, 
whether or not related to the investigational medical device (IMD). 
Note: 
1. This definition includes events related to the IMD. 
2. This definition includes events related to the procedures involved. 
3. For users or other persons, this definition is restricted to events related to the IMD. 
12.1.1 
Details of an AE 
The period of observation for an AE extends from when the ICF is signed until the subject’s 
last study visit. Any untoward medical occurrence that happens between the time ICF is 
signed and the first treatment with the IMD is an AE and has to be documented in the 
subject’s file and on the AE eCRF. Any observed AE will be fully investigated, 
documented, and followed until the event is either resolved or adequately explained. 
In cases of surgical or diagnostic procedures, the condition/illness leading to such a 
procedure is considered the AE rather than the procedure itself. New AEs reported to the 
investigator during the observational period, after the last treatment with the IMD, must be 
documented, treated, and followed like all other AEs. 
Treatment-emergent adverse events (TEAEs) are defined as AEs with onset at or after the 
first administration of study treatment. 
Pre-existing conditions noted in the medical history should not be reported as an AE, unless 
the condition worsens or the disease reoccurs during the reporting period. To determine 
whether a condition has worsened, it is compared to the subject’s condition at screening. 
Elective treatments planned before screening, and which are documented in the subject’s 
source data, are not regarded as AEs. However, elective procedures should be postponed, 
if possible, until the subject completes their participation in the study. 
12.1.2 
Reporting and Handling of an AE 
Data pertaining to AEs will be collected during each clinical study visit based on the 
subject’s spontaneous description, through investigator inquiry, or discovered in the course 
of examinations completed during the visit. The investigator will assess and record any AE 

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in detail in the subject file, and for all randomized subjects, on the AE eCRF. The following 
information must be recorded: 
• AE diagnosis or main symptom; 
• Location of AE: systemic or restricted to treatment area. If a local reaction, the 
corresponding area should be reported; 
• Date of onset; 
• Intensity (maximum observed; see Section 12.1.3); 
• Causal relationship (not related, related; see Section 12.1.4); 
• Serious (yes or no); 
• Outcome (see Section 12.1.5); 
• AE leading to discontinuation of the clinical study (yes or no); 
• Action taken with medical device; and 
• Stop date. 
In cases of a serious adverse event (defined in Section 12.2), the investigator must also 
complete an SAE Report Form and report it to the sponsor within 24 hours, as described in 
Section 12.2.2. 
12.1.3 
Severity Grading for an AE 
The clinical severity (i.e., intensity) of an AE will be classified as: 
Mild: 
Signs and symptoms that can be easily tolerated. Symptoms can be ignored 
and disappear when the subject is distracted. 
Moderate: Signs and symptoms that cause discomfort and interfere with normal 
functioning but are tolerable. They cannot be ignored and do not disappear 
when the subject is distracted. 
Severe: 
Signs and symptoms that affect usual daily activity and incapacitate the 
subject, thereby interrupting his/her daily activities. 
The investigator is required to grade the severity (i.e., intensity) of each AE. 
12.1.4 
Causal Relationship of an AE with an Investigational Medical 
Device 
An AE is considered to be “related” to IMD or the treatment procedure if a causal 
relationship between the IMD or the treatment procedure the AE is at least reasonably 

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possible (i.e., the relationship cannot be ruled out). In this case, the non-serious event is 
considered an “adverse device effect” (Section 12.3). If the event is serious, it is a “serious 
adverse device effect” (Section 12.4). 
The expression “reasonable causal relationship” is meant to convey that there are facts 
(evidence) or arguments to suggest a causal relationship. Otherwise, the relationship should 
be considered as “not related”. 
12.1.5 
Outcome Categories for an AE 
Reportable outcomes and/or sequelae of an AE may include the following: 
• Recovered/resolved. 
• Recovering/resolving. 
• Not recovered/not resolved. 
• Recovered/resolved with sequelae. 
• Fatal. 
• Unknown. 
If there is more than one AE, only the AE leading to death will be attributed with a “fatal” 
outcome. 
12.2 Definition of a Serious Adverse Event (SAE) 
An SAE is an adverse event that: 
1. led to death; 
2. led to serious deterioration in the health of the subject, that either resulted in: 
• a life-threatening illness or injury, or 
• a permanent impairment of a body structure or a body function, or 
• inpatient or prolonged hospitalization, or 
• medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
3. led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the 
clinical study protocol, without serious deterioration in health, is not considered a serious 
adverse event. 

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12.2.1 
Details of an SAE 
In cases of fatality, the cause of death is considered the AE, and the death is considered its 
outcome. In this case, the primary cause of death (i.e., the event leading to death) should 
be recorded and reported as an SAE. “Death” will be recorded as the outcome of this 
respective event; death will not be recorded as a separate event. Only if no cause of death 
can be reported (e.g., sudden death, unexplained death), the death per se might be reported 
as an SAE. In cases of death, an autopsy report should be submitted (if available). The date 
and cause of death should be recorded. 
Planned hospitalization for a pre-existing condition is not considered an SAE. If a subject 
experiences an additional AE that prolongs a pre-planned hospitalization, this event is 
considered an SAE and should be reported as such. Hospitalizations for elective treatments 
planned before screening and which are documented in the subject’s source data are not 
regarded as SAEs. 
In addition, device deficiencies, as defined in Section 12.5, that might have led to an SAE 
if: 
1. suitable action had not been taken, or 
2. intervention had not been made, or 
3. if circumstances had been less fortunate 
should be categorized as an SAE and reported accordingly. 
12.2.2 
Reporting and Handling of an SAE 
All SAEs that occur during the clinical study period, whether considered to be related to 
an IMD or not, must be reported via telephone, or e-mail and an SAE Report Form should 
be submitted to the sponsor within 24 hours of knowledge of the event. Further reporting 
details will be outlined in a separate document. 
Although all information required for completion of an SAE Report Form may not be 
available within the specified time period, an initial report should be submitted if the 
following minimal information is available: 
• An identifiable subject (unique subject number); 
• A suspect product and how the treatment is related to the SAE; 
• An identifiable reporting source (investigator/study site identification); and/or 
• An event or outcome that can be identified as serious. 

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The investigator must report SAEs to the sponsor as defined in Section 12.2 and the site’s 
IEC/IRB per their reporting guidelines. 
Within 10 working days after the sponsor first receives notice of the SAE, Merz Product 
Safety will conduct an evaluation of the SAE and report the results of such evaluation to 
regulatory agencies, IECs/IRBs, and investigators, as applicable. 
The investigator must supply further supporting information, and a detailed SAE 
description is an integral part of this supporting information. Follow-up SAE reports should 
be sent without delay to the sponsor or designee as an SAE Report Form (marked as a 
“follow-up” report), and the eCRF has to be updated accordingly to avoid discrepancies. 
The SAE has to be followed until the SAE is resolved / recovered or a plausible explanation 
is available. The SAE will be followed-up only in the Global Product Safety database after 
final SAE reconciliation is completed. 
SAEs occurring after the end of the observational period would need to be reported if the 
investigator considers the event to be related to IMD. These reports generally will not be 
entered into the investigation database. Following database lock for the study, any ongoing 
SAEs will be followed until resolution or stabilization under the responsibility of the 
investigator per his/her standard of care. 
The investigator should complete and send any SAE Report Forms or Pregnancy Forms 
(including any follow-up forms) to Merz North America Product Safety via the email 
provided below: 
Merz North America, Inc. Product Safety 
6501 Six Forks Road 
Raleigh, NC 27615 
USA 
 
Product Safety Email: AxUS-adverse.events@merz.com 
12.3 Definition of an Adverse Device Effect (ADE) 
An ADE is defined as an adverse event related to the use of an IMD. 
Note: 
1. This definition includes AEs resulting from insufficient or inadequate instructions for 
use, deployment, implantation, installation, or operation or any malfunction of the 
IMD. 
2. This definition includes any event resulting from use error or from intentional misuse 
of the IMD. 

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12.4 Definition of a Serious Adverse Device Effect (SADE) 
A SADE is defined as an adverse device effect that has resulted in any of the consequences 
characteristic of an SAE (Section 12.2). 
12.4.1 
Definition of an Anticipated Serious Adverse Device Effect 
(ASADE) 
An ASADE is a serious adverse device effect which by its nature, incidence, severity, or 
outcome has been identified in the current version of the risk-analysis report. 
12.4.2 
Definition of an Unanticipated Adverse Device Effect (UADE) 
A UADE is defined as follows: 
• Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), 
risk analysis report, or IFU. 
• Any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects. 
12.5 Definition of Device Deficiency 
A device deficiency is defined as an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. 
Note: Device deficiencies include malfunctions, use errors, and inadequate labeling. 
12.6 Definition of Technical Complaint 
A technical complaint, also referred to as a product complaint, is an apparent or suspected 
deficiency of a product in which the product does not meet its specification (e.g., leaking 
tube, incorrect product consistency, cracked vial). 
Note: The term “technical complaint” is synonymous with the term “device deficiency”. 
The term device deficiency is used in this study. 

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12.6.1 
Reporting and Handling of Device Deficiencies  
All device deficiencies shall be documented and reported by the investigator throughout 
the clinical investigation and appropriately reported to the sponsor. 
For reporting of device deficiencies: 
• For device deficiencies related to a specific subject’s treatment, a Device 
Deficiency eCRF must be completed and submitted by the investigative site, 
irrespective of the seriousness of the case. 
• For device deficiencies related to a specific subject’s treatment, a Device 
Deficiency eCRF must be completed and submitted by the investigative site, 
irrespective of whether the complaint led to an AE. All device deficiencies shall be 
documented and reported by the investigator throughout the clinical investigation 
and appropriately reported to the sponsor. The investigator will attempt to evaluate 
if the device deficiency might have led to an AE if suitable action had not been 
taken, intervention had not been made, or circumstances had been less fortunate. 
• If a device deficiency is associated with an SAE, the investigator must also 
complete and submit an SAE Report Form (see Section 12.2.2) in addition to the 
Device Deficiency eCRF. SAE Report Forms should be sent to Merz Product Safety 
for processing (see Section 12.2.2). 
• If a device deficiency is not related to a specific subject (e.g., damaged packaging 
occurring prior to the subject’s visit), the investigator should complete a paper 
device deficiency form (e.g., Device Technical Complaint Form), instead of the 
eCRF, and send to the sponsor within 24 hours to both their clinical study 
representative as well as to the Merz Technical Complaint Department for 
processing using the following email address: complaints2@merz.com 
The investigator should retain the device or needle or cannula in question for future 
inspection and investigation by the sponsor, if necessary. The Merz Technical Complaint 
Department will decide if the device or needle or cannula in question need to be returned 
and to whom they should be sent for investigation. 
12.7 Visual Safety Evaluation 
Any adverse event of visual disturbance including, but not limited to, any loss of vision, 
blurry vision, double vision, pain in or around eye (i.e., other than typical injection-induced 
pain), blind spot or shadow in the visual field, trouble moving eyes, etc. will be reported. 
The investigator will be instructed to report any AE of visual disturbance within 24 hours 
to the sponsor using the Report of Visual Disturbances Form. The incident will then be 
reported to FDA within 10 business days of receipt by the sponsor. These reports will be 
generated by the sponsor or designee and will include the depth of injection, injection 

Merz N ort h A merica, I nc.  
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M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 1  of 1 1 1  
v ol u me,  s y m pt o ms  o bser ve d,  ti me  t o  o nset  a n d  res ol uti o n,  a n d  a n y  i nter ve nti o ns  
i m ple me nte d. 
1 2. 9  R e p orti n g of Pr e g n a n c y  
A n y pre g na nc y t hat starts d uri n g t he cli nical st u d y  m ust be re p orte d, usi n g t he Pre g na nc y 
Re p ort  F or m,  b y  t he  i n vesti gat or  t o  t he  s p o ns or  wit hi n  2 4  h o urs  of  lear ni n g  of  its  
occ urr e nce. Pre g na nci es a n d pre g na nc y f oll o w -u p s h o ul d be re p orte d o n a Pre g na nc y 
Re p ort F or m.  Pre g na nc y  f oll o w -u p  s h o ul d  descri be  t he  o utc o me  of  t he  pre g na n c y,  
i ncl u di n g a n y v ol u ntar y or s p o nta ne o us disc o nti n uati o n; details of t he birt h; t he prese nce 
or  a bse nce  of  a n y  c o n ge nital  a b n or malities,  birt h  defects,  mater n al  or  ne w b or n  
c o m plicati o ns, a n d t heir relati o n t o t he I M D. I n a d diti o n, eac h pre g na nc y has t o be re p orte d 
o n t he A E e C R F (i. e.,  as  a n o n -s eri o us A E d u e  t o de vice  e x p os ure bef ore or  d uri n g 
pre g na nc y). Pre g n a nc y F or ms (i ncl u di n g a n y f oll o w- u p f or ms) s h o ul d be s u b mitte d t o t he 
c o ntacts refer e nce d i n Secti o n  1 2. 2. 2 . 
If  a  s u bject  bec o mes  pr e g na nt  d uri n g  t he  st u d y,  t he  s u bject  m ust  n ot  recei ve  f urt her  
treat me nts (t o uc h-u p or r etreat me nt) ; h o w e ver, t h e s u bject will re mai n i n t he st u d y. 
C CI

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13 STATISTICAL METHODS 
This section describes the statistical analyses foreseen at the time of study planning. Further 
details on the statistical and analytical aspects will be presented in the statistical analysis 
plan (SAP) that will be prepared and finalized prior to database close. 
Any deviations from planned analyses, the reasons for such deviation, and all alternative 
or additional statistical analyses will be described in amendments to the clinical study 
protocol and/or the SAP. All deviations and/or alterations will also be summarized in the 
clinical study report. 
Adequate descriptive statistics will be provided for each endpoint. Metric variables will be 
summarized by number of observations, mean, standard deviation, minimum, median, and 
maximum. Categorical variables will be summarized by frequencies and percentages per 
category where the denominator will be chosen according to the adequate analysis 
population. Ordered categorical data will be summarized by metric and categorical 
statistics, where appropriate. All variables will be analyzed as absolute data and as change 
from baseline, as applicable. Descriptive confidence limits (95%, two-sided) and 
descriptive p-values will be given, where appropriate. 
All data captured in the eCRF will be listed. 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), if on-site visits are not possible due to site closures, travel limitations, or other 
considerations (e.g., if site personnel or trial subjects become infected with SARS-CoV-2), 
the following mitigations should be considered and assessed in an updated SAP: 
• Describe changes to planned and additional analyses due to the public health 
emergency. Thoroughly assess drop-out patterns and sources of bias such as missing 
values and virtual instead of live assessments (if applicable). 
• Include systematic identification of protocol deviations due to the pandemic. 
• Consider the need for involvement of an independent Data Monitoring Committee 
particularly if trial sample size changes are anticipated. 
13.1 Randomization 
Subjects who complete all screening assessments and meet all eligibility criteria will be 
randomized to the following four groups: 
• Group TN: Treatment with BBL with needle at baseline; 
• Group TC: Treatment with BBL with cannula at baseline; 

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 3  of 1 1 1  
•  Gr o u p C D T N: U ntreat e d c o ntr ol u ntil Wee k 8 / Dela ye d -treat me nt B B L wit h nee dle 
(starti n g at Wee k 8); 
•  Gr o u p C D T C: U ntreate d c o ntr ol u ntil Wee k 8 / D ela ye d -treat me nt B B L wit h ca n n ula 
(starti n g at Wee k 8).  
Ra n d o mizati o n will be bl oc k -stratifie d b y i n vesti g ati o nal site, a n d gr o u ps will be assi g ne d 
via a n electr o nic s yste m li n ke d t o t he e C R F. At eac h st u d y site, t he n u m ber of s u bjects 
ra n d o mize d s h o ul d n ot e xcee d 2 6 t o e ns ure a reas o na ble distri b uti o n of s u bjects acr oss all 
i n vesti gati o nal sites. 
1 3. 2  E sti m ati o n of S a m pl e Si z e 
T he pri mar y effecti ve ness a nal ysis c o nsi ders t he  pr o p orti o n of s u bjects wit h at least 1- p oi nt 
i m pr o ve me nt o n t he MI H A S  f or b ot h I O Hs, as assesse d b y t he bli n de d e val uat or at Wee k  8 
c o m pare d t o bas eli ne  (see Secti o n  7. 2. 1. 1 ). F or t his a nal ysis, s u bjects fr o m T N a n d T C  
gr o u ps ( S ecti o n 1 3. 1 ) will be p o ole d i nt o t he Treat me nt Gr o u p (T R T ), a n d s u bjects fr o m 
C D T N a n d C D T C  gr o u ps ( data bef ore  a n y treat me nt) will be p o ole d i nt o t he C o ntr ol Gr o u p 
(C T L ). 
A t w o-ste p hierarc hical-testi n g pr oce d ure 
 Secti o n 1 3. 4. 1. 1 ) is f oresee n f or 
t he pri mar y a n al ysis: 
1.  T reat me nt Gr o u p ( T R T ) s h o ws a res p o nse rate of m ore t ha n  5 0 %, a n d 
2.  T reat me nt Gr o u p ( T R T ) is s u peri or t o t he C o ntr ol Gr o u p ( CT L ). 
T his hierar c hical -testi n g pr oce d ure will kee p t he o verall o n e-si de d err or rat e of α = 0. 0 2 5, 
a n d no a d j ust me nt f or m ulti plicit y is necessar y.  
Sa m ple size esti mati o n is base d o n met h o ds i m ple me nte d f or t he bi n o mi al a n d Fis her’s 
e xact  test.  I n  t his  c o nte xt  it  s h o ul d  be  n ote d  t hat  t he use  of  t w o-si de d  9 5 % Wils o n 
c o nfi de nce i nter vals  ( CI) a n d Ne wc o m be CI s, i nstea d of bi n o mial a n d Fis her’s e xact tests 
later o n, will deli ver m or e effi cie nt res ults (s maller CI s). T he CI b ase d met h o ds ha ve t he 
a d va nta ge t hat t he y  ca n be use d f or m ulti p le i m p utati o n o f missi n g d ata. He nce, s a m ple 
size cal c ulati o ns  ar e base d  o n sli g htl y m ore c o nser vati ve test  pr oce d ures,  s o t hat t he  
deter mi ne d p o wer will als o s uffice f or  tests base d o n  CI s. 
Sa m ple -size esti mati o n f or test S te p 1 is perf or me d wit h a o ne-si de d bi n o mial test at a n 
err or le vel of 2.5 % t o e v al uate w h et her t he res p o nse rat e is si g nifica ntl y l ar ger t ha n 5 0 %. 
It is ai me d t o e ns ure a p o wer of 9 0 %. T he bi n o mial test is c o n d ucte d t o t he p o ole d data 
( T R T) fr o m b ot h treat me nt gr o u ps (T N a n d T C ). D ue t o t he all ocati o n rati o of 2: 2: 1: 1, t he 
t w o treat me nt gr o u ps ( T N a n d T C) will be a p pr o xi matel y  e q uall y re prese nt e d. Calc ulati o ns 
f or test S te p 2 are perf or me d  wit h a o ne -si de d Fis her’s e xact test f or u ne q ual n’s, at a n err or 
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 4  of 1 1 1  
le vel of 2.5 %, t o detect a statisticall y si g nifica nt differ e n ce bet wee n a res p o nse rate i n 
Gr o u p T R T of 7 0 % c o m pare d t o 3 0 % i n Gr o u p C T L. A p o wer of at least 9 0 %  is ass u me d. 
Base d o n data fr o m a pil ot st u d y i n t he sa me i n dicati o n  ( M 9 3 0 1 2 1 0 0 1) s h o wi n g res p o n der 
rates of a b o v e 8 0 % f or o bser ve d data a n d a b o ve 7 0 % wit h missi n g data treate d as n o c ha n ge 
fr o m  baseli ne  ( n o  r es p o nse),  a  tr ue  res p o n der  rate  of  7 0 %  f or  t his  p o ole d  sa m ple is 
ass u me d. U n der t hese ass u m pti o ns, a t otal of 8 0 s u bjects are nee de d t o reac h a p o wer of at 
least 9 4 % i n test Ste p  1. 
F or t est Ste p  2 a n d mai ntai ni n g t he ass u m pti o n t o ha ve 7 0 % res p o nse rate i n t he treat me nt 
gr o u p a n d 3 0 % i n t he c o ntr ol gr o u p, a sa m ple size of 8 0 s u bjects i n Gr o u p T R T a n d 4 0 
s u bjects i n Gr o u p C T L  will reac h a p o wer of at least 9 8 % t o de m o nstrate statisticall y 
differe nt res p o nse rates b et wee n t he gr o u ps 
 
T o  acc o u nt  f or  u p  t o  2 0 %  dr o p- o uts,  1 5 0  s u bj ects  will be  ra n d o mize d  i n  t his  st u d y  
(i.e., 5 0 s u bjects i nt o eac h treat me nt gr o u p [T N  a n d T C ] a n d 2 5 s u bjects t o  eac h c o ntr ol 
gr o u p [ C D T N a n d C D T C ]). T he c o nser vati ve a p pr oac h of t his hierarc hi cal -test pr oce d ure 
will ha ve a n o ver all p o w er of a b o v e 9 2 %. 
If 1 5 0 s u bjects ar e treat e d, t he sa m ple size is s ufficie nt t o o bser ve, wit h a pr o ba bilit y of 
8 0 %, at least o ne A E  wit h act ual e v e nt pr o ba bilit y of 1. 1 %. 
S a m ple size calc ulati o ns 
 were perf or me d usi n g n Q uer y s oft w are (V ersi o n 8, 
Statistical S ol uti o ns Lt d. , 2 0 1 7)
ill ustrat es t he t w o hierarc hical -test ste ps f or t he 
pri mar y effecti ve n ess a n al ysis . 
1 3. 3  P o p ul ati o n s f or A n al y si s  
I n a d diti o n t o ra n d o mizati o n gr o u ps (T N , T C , C D T N a n d C D T C; see Secti o n 1 3. 1 ), t he 
f oll o wi n g a nal ysis gr o u ps will be defi ne d f or ra n d o mize d s u bjects as f oll o ws:  
•  T R T : All s u bjects fr o m T N a n d T C gr o u ps; 
•  C T L: All s u bjects fr o m C D T N a n d C D T C  gr o u ps wit h data  u ntil first treat me nt;  
C CI
C CI
C CI
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 5  of 1 1 1  
•  D T N: S u bset of s u bjects wit hi n C D T N wit h data  c ollecte d fr o m first treat me nt o n; 
•  D T C: S u bset of s u bjects wit hi n C D T C wit h data  c ollecte d fr o m first treat me nt o n; 
•  D T R T: Dela ye d -tr eat me nt gr o u ps D T N a n d D T C will be p o ole d fr o m C D T N a n d 
C D T C gr o u ps ( Not e : t hese s u bjects a n d t heir dat a u ntil t he first treat me nt will be part 
of t he u ntreat e d C T L gr o u p ); 
•  N E D: S u bjects t hat recei ve treat me nt wit h nee dle-i njecti o n tec h ni q ue will be p o ole d 
fr o m T N a n d D T N gr o u ps; 
•  C A N: S u bjects t hat recei ve treat me nt wit h ca n n ula-i njecti o n tec h ni q ue will be p o ole d 
fr o m T C a n d D T C gr o u ps; a n d 
•  T O T T: S u bjects t hat recei ve treat me nt at a n y ti me d uri n g t he st u d y ( T R T a n d D T R T)  
will be p o ole d fr o m N E D a n d C A N gr o u ps. 
T he f oll o wi n g a nal ysis sets will be defi ne d f or statistical a nal ysis:  
•  T he   i nte nt-t o-treat( 1)  (I T T( 1)) p o p ulati o n will i ncl u de all ra n d o mize d s u bj ects   of  t he 
u ntreate d -c o ntr ol gr o u p ( C T L) a n d all ra n d o mize d a n d treate d s u bj ects of t he treat me nt 
gr o u p ( T R T) . 
•  T he   i nte nt-t o-treat( 2)  (I T T( 2)) p o p ulati o n  will  i ncl u de  all  ra n d o mize d  a n d  treate d  
s u bjects of t he  treat me nt gr o u p ( TR T)  as well as all ra n d o mize d a n d treat e d s u bjects of 
t he dela ye d-treat me nt gr o u ps ( D T R T). 
•  T he Per Pr ot oc ol ( P P) p o p ulati o n is a s u bset of s u bjects i n t he I T T ( 1) p o p ulati o n wit h o ut 
maj or pr ot oc ol de viati o ns. Fi nal deter mi nati o n of w hat c o nstit utes a maj or pr ot oc ol 
de viati o n lea di n g t o e x cl usi o n fr o m P P p o p ulati o n will be ma de i n a d ata re vi e w 
meeti n g pri or t o data bas e cl ose. 
•  T he  Safet y p o p ulati o n ( S P) will c o nsist of all s u bjects treat e d. 
S u bjects i n a nal yses bas e d o n I T T a n d P P will be a nal y ze d as ra n d o mize d  a n d s u bjects 
a nal yze d i n t he S P will be a nal yze d as treate d . 
1 3. 4  A n al y si s of St u d y D at a  
Eff ecti ve n ess a n d safet y e n d p oi nts are pr o vi de d i n Secti o ns  7. 2. 1  a n d 7. 2. 2 . 
1 3. 4. 1  
Eff e cti v e n e s s  An al y s e s  
 ill ustrates t h e ti me p oi nts a n d t he a nal ysis gr o u ps t o b e us e d f or t h e effecti ve ness 
a nal yses.  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 6  of 1 1 1  
1 3. 4. 1. 1  
P ri m ar y Eff e cti v e n e s s E n d p oi nt  
T he pri mar y eff ecti ve n ess e n d p oi nt  (Secti o n 7. 2. 1. 1 ) will be s u m marize d as c o u nts a n d 
perce nt a ges f or t he  p o ole d treat me nt gr o u p (T R T ) a n d t he p o ole d c o ntr ol gr o u p (C T L ). 
F o ur h y p ot hesis tests will be perf or me d , b ase d o n  t he pri mar y effecti ve ness e n d p oi nt. 
T hese tests will be e val u ate d  i n a s e q ue ntial or d er o n t he I T T ( 1) p o p ulati o n. T o c o ntr ol f or 
m ulti plicit y, a hierarc hical -testi n g pr oce d ure will be perf or me d. Eac h test will here b y be 
perf or me d  at a o n e- si de d α  le vel of 0. 02 5. T he first t w o tests f or t he pri mar y e n d p oi nt of 
treat me nt vers us c o ntr ol will be c o nfir mat or y test s as o utli ne d i n 
; if b ot h n ull 
h y p ot heses ar e r eject e d, t w o a d diti o nal tests will be perf or me d, as s u b gr o u p a nal yses , t o 
i n vesti gate t he eff ecti ve n ess of t w o  i njecti o n tec h ni q ues (i.e., nee dl e a n d ca n n ula). 
C CI
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 7  of 1 1 1  
Pri m ar y a n al yses  
T he first h y p ot hesis  test of t he pri mar y a nal ysis e val uates w het h er  t he res p o nse rate i n 
treate d s u bjects fr o m T R T is si g nifica ntl y lar ger t ha n 5 0 %. T he sec o n d h y p ot hesis test 
e val uates  w h et her  t h e  r es p o nse  rat e  i n  treat e d  s u bjects  fr o m  T R T  is  hi g her  t ha n  t he  
res p o nse r ate i n u ntr eate d s u bjects fr o m t he c o ntr ol gr o u p C T L. B ot h h y p ot heses will be 
teste d  usi n g  t he  l o w er  li mits  of  t he  9 5 %  CIs  (t w o-si de d),  b ase d  o n  Wils o n  sc ores.  
T he  l o wer li mit of t he 9 5 % Wils o n CI m ust e xcee d t he mar gi n of 5 0 % res p o n der rate t o 
reject H y p ot h esis 1 (H 1 0). T he l o wer li mit of t he 9 5 % Ne w c o m be CI m ust be greater t ha n 
zer o t o r eject H y p ot hesis 2 ( H 2 0). 
Usi n g t he Wils o n a n d Ne wc o m be CIs i n t hese tests will all o w f or i m p utati o n of missi n g 
val ues  of  t h e  pri mar y  effecti ve ness  e n d p oi nt  wit h  a  m ulti ple -i m p utati o n  a p pr oac h.  
T his  pr oce d ur e will re place missi n g MI H A S val ues at Wee k 8 f or t he I T T( 1) p o p ulati o n. 
S A S P R O C MI will b e us e d t o create m ulti ple sets wit h i m p ute d MI H A S sc ores per gr o u p. 
Baseli ne MI H A S, Wee k 4 MI H A S, p o ole d site (f or p o oli n g details, see s u b gr o u p a nal yses 
bel o w) a n d t o uc h- u p ( yes/ n o) will be i ncl u de d i n t he m ulti ple-i m p utati o n m o del. F or eac h 
data  set , t he  Wils o n  CI  will  be  c o m p ute d  a n d  later  c o m bi ne d  usi n g  S A S  P R O C  
MI A N A L Y Z E. T he n, t h e li mits of t he t w o res ulti n g c o m bi ne d Wils o n CIs f or T R T a n d 
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 8  of 1 1 1  
C T L will be us e d t o c o m p ute t he Ne w c o m be CI f or t he res p o n der rate differe nce b et wee n 
t he gr o u ps. 
S u b gr o u p a n al yses 
If b ot h alter n ati ve h y p ot heses i n t he pri mar y a n al ysis are acce pte d, a d diti o nal h y p ot hes es 
testi n g will be perf or me d t o e val uate w het her treat me nt wit h ca n n ula-i njecti o n tec h ni q ue 
a n d treat me nt wit h n ee dle-i njecti o n  tec h ni q u e are s u peri or o ver c o ntr ol as dis pla ye d i n 
 test S te ps 3 a n d 4. 
C CI
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 7 9  of 1 1 1  
F urt her m ore, r es p o ns e r ates f or T R T, C T L as well as t he differe n ce of res p o nse rates 
bet wee n  T R T  a n d  C T L,  i ncl u di n g  c orres p o n di n g  9 5 %  CIs  will  be  pr o vi de d  f or  t h e 
f oll o wi n g s u b gr o u ps: baseli ne MI H A S, ge n der, a n d Fitz patric k S ki n T y pe (I -III vs. I V-VI) . 
1 3. 4. 1. 2  
S e c o n d ar y Eff e cti v e n e s s E n d p oi nt s 
If n ot ot her wise s pecifie d, sec o n dar y effecti ve ness a nal yses will be c o n d ucte d base d o n 
o bser ve d cases f or t he I T T ( 1) a n d P P p o p ulati o n  f or s u bjects of treat me nt gr o u ps T N a n d 
T C a n d of p o ole d treat me nt gr o u p T R T o nl y. 
S u b gr o u p a n al yses 
I n a d diti o n t o t he o v er all s u m mar y statistics defi ne d a b o ve, s u m mar y statistics will als o b e 
pr o vi de d f or t he s a me s u b gr o u ps  as  a nal y ze d  f or t he pri mar y effecti ve ness e n d p oi nt:  
baseli ne MI H A S , ge n d er, a n d Fitz patri c k S ki n T y pe (I-III vs. I V-VI).  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 8 0  of 1 1 1  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 8 1  of 1 1 1  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 8 2  of 1 1 1  
C CI

Merz N ort h A merica, I nc.  
C LI NI C A L S T U D Y P R O T O C O L  
M 9 3 0 1 2 1 0 0 2  
Versi o n 5. 0, 0 4- N O V -2 0 2 1  
C O N FI D E N TI A L  A N D P R O P RI E T A R Y  
Pa ge 8 3  of 1 1 1  
1 3. 4. 2  
S af et y A n al y s e s  
All  safet y  e n d p oi nts  will  be  s u m marize d  f or  o bser ve d  val u es  i n  t he  S P  b y  i njecti o n  
tec h ni q ue  ( gr o u ps  N E D  a n d  C A N)  a n d  o v erall  ( T O T T),  if  n ot  ot her wise  stat e d.  
A d verse e ve nts f or t he u ntreate d c o ntr ol gr o u p ( C T L) u ntil Wee k 8, will be liste d a n d 
s u m marize d se par atel y s h o wi n g n u m ber of s u bjects wit h A Es a n d n u m ber of A Es b y 
s yste m or ga n class ( S O C) a n d preferre d ter m ( P T) . 
All A Es will be c o de d acc or di n g t o t he Me dical Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A) versi o n i n eff ect at t he ti me t he data b ase is l oc ke d. 
I n t he e C R F, A Es will be re p ort e d wit h t heir o nset a n d f urt her w orse ni n g, if re q uire d. 
F or  a n al ysis, eac h d oc u me nte d w orse ni n g of a n A E will be a g gre gate d wit h t he pre vi o us 
c orres p o n di n g A E rec or d. T he start date of t he A E will be t he date of t he rec or d re p orti n g 
t he o nset of t he A E a n d t he st o p dat e will b e t he st o p date of t h e last w orse ni n g rec or ds or 
o n g oi n g, if n ot yet res ol ve d. F or seri o us ness, i nte nsit y, ca usal relati o ns hi p, a n d o utc o me 
t he  w orst  attri b utes  will  be  a nal yze d.  All  ot her  A E  attri b utes  will  be  a p pr o priatel y  
c u m ulate d fr o m all r e p orte d rec or ds.  
T here is o n e e xce pti o n, w here  a n a g gre g ati o n wit h t he pre vi o us rec or d(s) is n ot all o we d: if 
t he pre vi o us A E r ec or d(s) starte d b ef ore t he first treat me nt a n d t he w ors e ni n g rec or d start e d 
( w orse n e d) at or after d ate of first treat me nt. I n t his case, o nl y t he A E rec or d(s) starti n g at 
or after treat me nt will be a g gre gate d a n d re gar d e d as  treat me nt e mer ge nt a d verse e v e nts 
(T E A E ; see b el o w). 
T E A Es ar e defi n e d as A Es wit h o nset at or after t he first a d mi nistrati o n of st u d y treat me nt 
(Secti o n 1 2. 1. 1 ).  O nl y  T E A Es a n d  T E S A Es  will  be  a n al yze d. T his  will  be  d o ne  b y  
C CI

Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
M930121002 
Version 5.0, 04-NOV-2021 
CONFIDENTIAL AND PROPRIETARY 
Page 84 of 111 
treatment cycle (see treatment cycles in Section 13.4.1.3). Hereby the following 
assignments will be made: 
• For subjects of groups TN or TC, TEAEs will be grouped into two treatment cycles 
according to the AE onset date, as follows: 
o For subjects without retreatment: 
An AE is considered treatment emergent for Cycle 1 if the start date of the AE is 
on or after the date of the initial treatment injection and before end of the study. 
o For subjects with retreatment: 
An AE is considered treatment emergent for Cycle 1 if the start date of the AE is 
on or after the date of the initial injection and before the date of the retreatment. 
An AE is considered treatment emergent for Cycle 2 if the start date of AE is on or 
after the date of the retreatment and before end of the study. 
• For subjects of groups DTN and DTC, an AE is considered treatment emergent for 
Cycle 1 if the start date is on or after the date of delayed treatment at Week 8. 
All other AEs are considered to be non-TEAEs (i.e., all AEs with start date prior to initial 
injection). 
An overall AE summary table will be provided by treatment cycle or overall as appropriate, 
displaying the following content: 
• Any AEs; 
• Any non-TEAEs; 
• Any TEAEs; 
• Any related TEAEs; 
• Any TESAEs; 
• Any related TESAEs; 
• Any TEAEs leading to discontinuation from study; and/or 
• Any TEAEs leading to discontinuation of study treatment. 
For TEAEs, related TEAEs, TESAEs, and related TESAEs, number of subjects with 
TEAEs and number of TEAEs will be summarized by SOC and PT, by treatment cycle or 
overall as appropriate. 
In addition, the following TEAE incidences will be shown by treatment cycle or overall as 
appropriate: 

Merz North America, Inc. 
CLINICAL STUDY PROTOCOL 
M930121002 
Version 5.0, 04-NOV-2021 
CONFIDENTIAL AND PROPRIETARY 
Page 85 of 111 
• TEAEs, number of subjects with TEAEs by PT; 
• TEAEs by worst intensity, number of subjects with TEAEs by SOC and PT; 
• TEAEs by worst causal relationship, number of subjects with TEAEs by SOC and PT; 
• TEAEs by worst outcome, number of subjects with TEAEs by SOC and PT; and 
• TEAEs by maximum duration, number of subjects with TEAEs by SOC and PT 
(duration categories: 1 to 3 days, 4 to 7 days, 8 to 14 days, 15 to 28 days, and > 28 days). 
Duration of TEAEs will be calculated by the difference of start and stop date plus 1 day. 
Moreover, the AE overview table as well as incidences of related TEAEs (by PT and SOC) 
will be provided for the following subgroups, by treatment cycle: 
• Touch-up (yes/no) (applies to Cycle 1 only); 
• Gender; and 
• Fitzpatrick skin types (I, II, III and IV, V, VI). 
Incidences, maximum duration, and maximum severity of CTRs will be summarized for 
the initial treatment as well as for its corresponding touch-up injection (if applicable), 
delayed treatment and its corresponding touch-up injection (if applicable), and retreatment 
(if applicable) for the single treatment groups TN, TC, DTC and DTN. Additionally, CTR 
data may be summarized (as applicable) by pooling the initial injection data from the TRT 
and DTRT groups and pooling the touch-up data from the TRT and DTRT groups. 
Maximum duration will be calculated as the difference between the first date of CTR 
reporting and the last date of CTR reporting plus 1 day. Additional rules for handling 
missing eDiary entries will be specified in the SAP. Maximum duration categories will be 
defined as follows: 1 to 3 days, 4 to 7 days, 8 to 14 days, and 15 to 28 days. 
Listings for all AEs, as well as subsets including non TEAEs, AEs leading to 
discontinuation, SAEs, and deaths will be provided. Device deficiencies will also be listed. 
13.4.3 
Other Subject Data 
All demographic, baseline characteristics, and subject disposition data will be presented 
using standard descriptive statistics. Demographic data will be summarized for all screened 
subjects and the SP, ITT(1), ITT(2), and PP populations. The remaining baseline data will 
be summarized descriptively only for the ITT(1), ITT(2), and PP populations, as applicable. 
Subject disposition (i.e., number of subjects screened, randomized, and treated, as well as 
the number of subjects in each analysis population) will be summarized by various groups 
(i.e., TN, TC, TRT, CTL, DTN, DTC, DTRT, NED, CAN, TOTT). Additionally, the 
number of subjects expected at a visit and attended a visit will be summarized. 

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Frequencies of concomitant treatments will be given based on different Anatomical 
Therapeutic Chemical (ATC) Classification System code levels for the SP. Indications for 
concomitant therapies will not be coded and will only be listed. 
Medical history and concomitant diseases will be coded using the MedDRA dictionary and 
reported by SOC and PT levels for the SP. 
13.5 Special Statistical/ Analytical Issues 
13.5.1 
Subject Discontinuation and Missing Data 
Methods intended for handling of missing primary effectiveness endpoint data are 
described in Section 13.4.1.1. 
Handling of missing scores of FACE-Q Satisfaction with Eyes scores is described in 
Section 13.4.1.2. Handling of missing scores of FACE-Q Appraisal of Lower Eyelids is 
described in Section 13.4.1.3. 
For remaining endpoints, observed cases will be analyzed, if not otherwise specified. 
Additional rules for handling missing eDiary entries will be specified in the SAP. 
13.5.2 
Interim Analyses 
No interim analyses are planned. 
Data listings pertaining to annual FDA reporting updates will be produced as necessary. 
At a minimum, annual reports will contain enrollment updates (i.e., number of subjects 
recruited at each site, number screened and enrolled, number randomized, etc.), subject 
disposition, and safety listings. 
13.5.3 
Other Planned or Subgroup Analyses 
Subgroup analyses are described for the primary effectiveness endpoint in Section 13.4.1.1 
and for the secondary effectiveness endpoints in Section 13.4.1.2. 
Subgroup analyses for safety are described in Section 13.4.2. 

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14 ADMINISTRATIVE PROCEDURES 
14.1 Study Monitoring 
Study monitoring will conform to all applicable regulatory standards and guidelines. 
The sponsor or designee will monitor the study through periodic site visits to verify: 
• Data authenticity, accuracy, and completeness. 
• Protection of subject rights and safety. 
• Conduct of the study is in accordance with the currently approved protocol and all 
applicatory regulatory requirements and guidelines. 
Investigators agree to grant access to all relevant documents and provide support at all 
times for study monitoring activities. Study monitoring activities will be performed in a 
manner that ensures maintenance of subject confidentiality (Section 5.3). 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), and by this, if on-site visits are not possible due to site closures, travel 
limitations, or other considerations (e.g., if site personnel or trial subjects become infected 
with SARS-CoV-2), the following mitigations should be considered and assessed in an 
updated monitoring plan: 
• On-site monitoring visits might be cancelled and/or the period between monitoring 
visits extended. When planned on-site monitoring visits are not possible, the reason 
should be clearly documented and made available for review during audits and/or 
inspections. 
• Phone and/or video visits will be implemented when feasible, considering site 
closures, reduced staff, and any other circumstances. 
• Remote monitoring or central monitoring could substitute on-site monitoring, when 
technically feasible. 
• Protocol deviations will be tracked and documented if deviations occurred due to 
the public health emergency. 
Current local regulations, including data privacy regulations will be considered when 
accessing source data remotely. 
14.2 Data Quality Assurance 
Inspections by regulatory authority representatives and IECs/IRBs are possible at any time, 
even after the end of the study. The investigator is to notify the sponsor immediately of any 

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such inspection. The investigator and institution will permit study-related monitoring, 
audits, reviews by the IEC/IRB and/or regulatory authorities and will allow direct access 
to source data and source documents for such monitoring, audits, and reviews. 
14.2.1 
Standardization Procedures 
Standardization procedures will be implemented to ensure accurate, consistent, complete, 
and reliable data, including methods to ensure standardization among sites (e.g., training, 
newsletters, investigator meetings, monitoring, centralized evaluations, and validation 
methods). Standardized photography methods are detailed in a separate photography user 
manual. 
This study will be monitored regularly by a qualified monitor from the sponsor/CRO/or 
designee according to GCP guidelines and the respective SOPs (see Section 14.1). 
14.2.2 
Source Documentation Requirements 
All data collected from a subject during the course of a clinical investigation should be 
retained in the respective source documentation (e.g., subject file). This includes a copy of 
the letter sent to the subject’s primary physician about the subject’s participation in the 
investigation (provided the subject has a primary physician and has agreed to the primary 
physician being informed). The source documentation must also contain a descriptive 
statement on the informed-consent procedure. The investigator must also confirm by 
written statement in the source documentation that all inclusion criteria and all exclusion 
criteria were checked prior to inclusion of the subject. In addition to this statement, the 
subject’s meeting or non-meeting of the and eligibility criteria have to be traceable on the 
basis of the documentation in the subject’s file. The childbearing potential of female 
subjects must be noted in the source documentation. The site will keep a source data 
location list, which will outline for the different (electronic) data categories (e.g., 
demographics, medical history, and adverse events, etc.) which document serves as source 
for these data (e.g., subject file, subject eDiary). 
If an investigational site is using an electronic system for documenting source data, a 
member of the site staff must print out the source data after each visit. The paper print-outs 
must be overlapping, if possible (i.e., must contain at least the last row of data from the 
subject’s previous visit). If it is not possible to obtain overlapping paper print-outs, the 
completeness of source data must be ensured by other suitable means. The print-out must 
be signed and dated by a member of the site staff who can confirm the accuracy and 
completeness of data in the paper print-out. The monitor should also sign and date after 
verifying the source data. The paper print-out should be stored in the Investigator Site File. 
If source data information is entered retrospectively, this must be done directly on the paper 
print-out and should be initialed and dated. The same applies to any corrections of initial 
data. 

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If the site is using a validated computer system including audit trail with an adequate access 
for the monitor (i.e., the monitor can only access the data of the investigation subjects), 
then no such paper print-outs are required. The monitor should perform spot-checks in the 
electronic system to confirm that the process of generating paper print-outs by site staff is 
comprehensive and reliable. 
14.2.3 
Data Management 
Systems (e.g., eCRF, eDiary) used for electronic data capture fulfill all requirements from 
21 CFR Part 11. 
Data required for reporting according to this protocol are to be recorded in the web-based 
eCRFs, ClinCase, provided by a CRO. All users who will enter data into the eCRF must 
successfully complete training before system access is granted. Participant training will be 
documented. Access to the eCRF will be password controlled. By electronically signing 
the eCRF, the investigator will confirm that all investigations have been completed and 
conducted in compliance with the protocol. 
Data-plausibility checks will be performed according to a data-validation plan. 
Inconsistencies in the data will be queried to the investigators via the EDC system; answers 
to queries or changes to the data will also be documented in this system directly by an 
authorized member of the investigator’s site staff. The audit trail in the EDC system will 
document all changes. Edit checks generate automatic queries during data entry when 
applicable. Manual queries to be answered by site staff can be raised during source-data 
verification and/or during medical, safety, and/or data management review. After all data 
are entered and all queries are resolved, the database will be closed. If any data changes 
are required after database close, these changes will be documented according to the 
respective SOP. Further details of the data management process will be described in the 
data management plan. 
Photographs will be archived by the central photography vendor in system separate from 
the database (see Section 14.3). eDiary data will be transferred electronically to the data 
management CRO. Checks will be performed to ensure plausibility and completeness of 
these data. The data management activities and photographs processing will be delegated 
to the CROs listed in Section 16.6. 
In the event of a pandemic disease outbreak (e.g., new COVID-19 public health 
emergency), and by this, if data entry and cleaning is limited or not possible due to site 
closures, travel limitations, or other considerations (e.g., if site personnel become infected 
with SARS-CoV-2), the following mitigations should be considered for data cleaning 
processes: 
• Data entry and response to data clarifications will proceed depending on availability 
of study nurses, coordinators, and investigators. 

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• Depending on the content of data clarifications, the necessity for source data review 
will be assessed by the sponsor. 
• Self-evident corrections of obvious query responses will be allowed. These will be 
documented thoroughly (e.g., using a list of self-evident corrections to be approved 
before Database Lock). 
• If applicable, risk-based assessment of closing long open queries will be done 
considering their impact on trial conclusion and data validity. 
• Assessment will be completed to determine if data clarifications and/or eCRF pages 
are to be signed by staff that is not yet on the delegation log. The delegation log is 
to be updated, if applicable. 
14.2.4 
Auditing 
To ensure compliance with applicable standards and regulations, the sponsor, IEC/IRB, or 
regulatory authorities may conduct a quality assurance assessment or audit of site records 
at any time during or after completion of the study. In the event of an audit, investigators 
must grant access to all relevant documents (including source documents, electronic 
records, and other applicable study documentation) and provide support at all times for 
auditing activities. 
14.3 Record Retention 
Essential documents should be retained per applicable regulations and as instructed by the 
study sponsor. Essential documents at the investigational site include but are not limited 
to: 
• Subject files; 
• Subject identification code list; 
• A copy of the study protocol and any amendments; 
• Investigator’s copies of the eCRFs and any associated subject-related source data; 
• Signed ICFs; 
• Copies of all direct correspondence with the IEC/IRB and with the regulatory 
authority(ies), and with the sponsor; 
• Copies of any photographs; and 
• Copies of investigational device disposition records. 
Study documents may not be destroyed by study-site personnel prior to the end of the 
required retention period as specified by local regulations. The investigator or the 

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institution must inform the sponsor in due time if the investigator leaves the institution 
during the retention period. This rule also applies when the institution closes within the 
retention period. 
Upon closure of the study, the investigator must maintain all study-site records in a safe 
and secure location. The investigator is responsible for the integrity, retention, and security 
of all study-related records. The investigator must ensure that any reproductions of the 
original records are legible and provide a true and accurate copy of the original. 
Accurate, complete, and current records must be stored in such a way as to permit easy and 
timely retrieval for the sponsor or any applicable regulatory authorities. 
The sponsor will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements, with the minimum retention time being 
the longest of those times dictated by institutional requirements, local laws or regulations, 
or the sponsor’s standard procedures. The investigator must notify the sponsor in the event 
of any changes to archival arrangements due to withdrawal of the investigator’s 
responsibility for keeping study records to ensure that suitable arrangements for the 
retention of study records are made. 
14.4 Publication Policy 
The results of this study and any discoveries related to this study, regardless of whether 
they have technical or medical character, are the property of the sponsor. 
The study protocol, study data, and information related the study or the sponsor’s products 
or research programs are to be kept confidential and may not be disclosed without the 
consent of the sponsor. The investigators have the responsibility to provide complete study 
data, records, and reports for inspection by the appropriate regulatory authorities, the 
sponsor, or the IEC/IRB, as appropriate. 
The investigator agrees that the results of this study may be used for submission to national 
or international registration and supervising authorities. The sponsor may disclose the 
information obtained during the study to regulatory authorities or other personnel as 
required. If necessary, the sponsor may disclose the names, contact information, and 
qualifications of all investigators as well as their roles in the study. Upon completion of the 
study, publication or disclosure of the study results is to follow the terms contained in the 
sponsor’s publication policy. 
The sponsor will ensure that a description of this clinical study is registered, and study 
results are disclosed on http://www.ClinicalTrials.gov, as required by U.S. law. 
Study registration may include a list of study sites, as applicable. 

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14.5  Financial Disclosure 
The US FDA Financial Disclosure by Clinical Investigators (21 CFR 54) regulations 
require sponsors to obtain certain financial information from investigators participating in 
covered clinical studies. By participating in the study, the investigator agrees to provide 
the required financial information and to promptly update the sponsor with any relevant 
changes to this financial information throughout the course of the study and for up to one 
(1) year after its completion if necessary. 
14.6 Investigator Compliance 
The investigator will conduct the study in compliance with the protocol provided by the 
sponsor and in accordance with all relevant regulatory guidelines and requirements. 
Modifications to the protocol should not be made without the agreement of the investigator 
and sponsor. The sponsor will submit all protocol modifications to the appropriate 
regulatory authority in accordance with applicable regulations. All protocol modifications 
require written IEC/IRB approval/favorable opinion, except in the case of an immediate 
hazard to subjects. 
If an immediate deviation from the protocol is required to eliminate an immediate hazard 
to subjects, the investigator must contact the sponsor or assigned CRO, if possible, to 
discuss the planned course of action. The investigator must thoroughly document any 
departure from the protocol and submit appropriate documentation to the sponsor without 
delay. 

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15 REFERENCE LIST 
1. Alam M, Gladstone H, Kramer EM, Murphy JP, Jr., Nouri K, Neuhaus IM, et al. ASDS 
guidelines of care: injectable fillers. Dermatol Surg. 2008;34 Suppl 1:S115-48. 
2. Wewers ME, Lowe NK. A critical review of visual analogue scales in the measurement 
of clinical phenomena. Res Nurs Health. 1990;13(4):227-36. 
3. Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue 
scales as ratio scale measures for chronic and experimental pain. Pain. 1983;17(1):45-56. 
4. Pincus T, Bergman M, Sokka T, Roth J, Swearingen C, Yazici Y. Visual analog scales 
in formats other than a 10 centimeter horizontal line to assess pain and other clinical data. 
J Rheumatol. 2008;35(8):1550-8. 
 

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16 APPENDICES