A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of QM1114-DP for the Treatment of Moderate to Severe Lateral Canthal Lines
Phase: PHASE3
Conditions: Lateral Canthal Lines
Sponsor: Galderma R&D

C O N FI D E N TI A L
Pa ge 1 of 8 7
C LI NI C A L S T U D Y P R O T O C O L
P R O T O C O L N U M B E R: 4 3 Q M 1 9 0 1
C O N FI D E N TI A L
T his d oc u me nt c o nt ai ns c o nfi de nti al, pr o priet ar y i nf or m ati o n
All t he i nf or mati o n pr o vi de d t o t he I n vesti gat or a n d his/ her staff a n d all data o btai ne d t hr o u g h t his 
Q- Me d A B cli nical st u d y pr ot oc ol are c o nfi de ntial.  Q-Me d A B is t he o w ner of all i nf or mati o n 
i ncl u de d i n t his pr ot oc ol as S p o ns or a n d t he S p o ns or reser ves all pr o prietar y ri g hts. N o i nf or mati o n 
ma y  
be 
discl ose d 
t o 
a n y 
thir d 
part y  
wit h o ut 
pri or 
writte n 
c o nse nt 
fr o m 
Q- M e d A B.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 2 of 8 7
TI T L E P A G E
A M ultice nter, Ra n d o mize d, D o u ble- Bli n d, Place b o -C o ntr olle d St u d y  t o E val uate t he Efficac y a n d 
Safet y  of Q M 1 1 1 4-D P f or t he Treat me nt of M o derate t o Se vere Lateral Ca nt hal L i nes
( R E A D Y – 2)
C li nic al Tri al N u m ber ( CT N ): 4 3 Q M 1 9 0 1
I N D N u m ber:
S P O N S O R:
Na me:
Q -Me d A B, a Gal der ma affiliate
A d dress:
Se mi narie gata n 2 1
S E -7 5 2 2 8 U p psala, S we de n
P h o ne:
+ 4 6 1 8 4 7 4 9 0 0 0
C O N T R A C T R E S E A R C H O R G A NI Z A TI O N ( C R O):
Na me:
A d dress:
P h o ne:
S A F E T Y:
F or safet y q uesti o ns, please c o ntact t he Safet y e mail or Me dical M o nit or usi n g t he details pr o vi de d 
i n Secti o n 1 1. 9 . Seri o us a d verse e ve nt s ( S A Es) a n d pre g na nc y re p ort f or ms s h o ul d be s u b mitte d as 
descri be d i n Secti o n s 7. 2. 6. 2. 2 a n d 7. 2. 6. 2. 3 .
M E DI C A L M O NI T O R:
F or a n y me dical q uesti o ns relate d t o t h e cli nical st u d y pr ot oc ol, please c o ntact t he Me dical M o nit or
usi n g t he details pr o vi de d i n Secti o n 1 1. 9 .
T his cli nical st u d y shall be perf or me d i n c o m plia nce wit h t he cli nical trial a gree me nt ( C T A), t he 
cli nical st u d y pr ot oc ol ( C S P), I CH -G o o d Cli nical Practice ( G C P),1 a n d a p plica ble re gi o nal a n d 
nati o nal re g ulati o ns. T he st u d y shall be c o n d ucte d i n acc or da nce wit h t he et hical pri nci ples t hat ha ve 
t heir ori gi n i n t he Declarati o n of Helsi n ki ( htt ps:// w w w. w ma. net/ p olicies-p ost/ w ma -declarati o n -of-
helsi n ki -et hical-pri nci ples -f or-me dical -researc h-i n v ol vi n g-h u ma n -s u bjects/).
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
P P D
C CI

C O N FI D E N TI A L
Pa ge 3 of 8 7
T a ble of C o nte nts
TI T L E P A G E .................................................................................................................................................. 2
S Y N O P SI S ...................................................................................................................................................... 9
C LI NI C A L S T U D Y S C H E M A TI C A N D F L O W C H A R T ...................................................................... 1 6
S C H E D U L E O F A S S E S S M E N T S .............................................................................................................. 1 8
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 9
1.
B A C K G R O U N D A N D R A TI O N A L E ........................................................................................ 2 3
1. 1
Me dic al B ac k gr o u n d a n d S h ort R ati o n ale f or t he Cli nic al St u d y ............................................ 2 3
1. 2
St u d y Pr o d uct Pr ofile ................................................................................................................... 2 4
1. 2. 1
Dr u g Pr ofile ..............................................................................................................................2 4
1. 2. 2
Pre -Cli n ic al D oc u me nt ati o n.................................................................................................... 2 4
1. 2. 3
Cli nic al D oc u me nt ati o n ........................................................................................................... 2 5
1. 2. 4
D ose R ati o n ale .......................................................................................................................... 2 6
1. 3
Ris k/ Be n efit Assess me nt ............................................................................................................... 2 6
2.
C LI NI C A L S T U D Y O B J E C TI V E S, E N D P OI N T S, A N D C LI NI C A L 
H Y P O T H E SI S ...............................................................................................................................2 6
2. 1
Cli nic al St u d y O bjecti ves ............................................................................................................. 2 6
2. 1. 1
Pri m ar y Effic ac y O bjecti ves a n d E n d p oi nts ......................................................................... 2 7
2. 1. 2
Sec o n d ar y Effic ac y O bjecti ves a n d E n d p oi nts ...................................................................... 2 7
2. 1. 4
S afet y O bjecti ves a n d E n d p oi nts ............................................................................................ 2 8
2. 2
Cli nic al H y p ot hesis ....................................................................................................................... 2 9
3.
O V E R A L L C LI NI C A L S T U D Y D E S C RI P TI O N ..................................................................... 2 9
4.
C LI NI C A L S T U D Y D U R A TI O N A N D T E R MI N A TI O N ....................................................... 3 0
5.
S E L E C TI O N A N D DI S P O SI TI O N O F C LI NI C A L S T U D Y P O P U L A TI O N ....................... 3 0
5. 1
N u m ber of S u bjects ....................................................................................................................... 3 0
5. 2
Cli nic al St u d y P o p ul ati o n C h ar acteristics .................................................................................. 3 0
5. 2. 1
I ncl usi o n Criteri a ..................................................................................................................... 3 1
5. 2. 2
E xcl usi o n Criteri a .................................................................................................................... 3 1
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
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C O N FI D E N TI A L
Pa ge 4 of 8 7
5. 3
Me dic al Hist or y ............................................................................................................................. 3 3
5. 4
Pre vi o us a n d C o nc o mit a nt T her a pies ......................................................................................... 3 3
5. 4. 1
Defi niti o n .................................................................................................................................. 3 3
5. 4. 2
C ate g ories ................................................................................................................................. 3 4
5. 4. 3
Rec or di n g .................................................................................................................................. 3 4
5. 4. 4
A ut h orize d C o nc o mit a nt T her a pies ....................................................................................... 3 4
5. 4. 5
Pr o hi bite d C o nc o mit a nt T her a pies ........................................................................................ 3 4
5. 5
Pr oce d ures/ Re as o ns f or S u bject Disc o nti n u ati o n ...................................................................... 3 5
6.
C LI NI C A L S U P P LI E S ................................................................................................................ 3 6
6. 1
Cli nic al S u p pl y I de ntific ati o n a n d Use ........................................................................................ 3 6
6. 1. 1
Q M 1 1 1 4 -D P ..............................................................................................................................3 6
6. 1. 2
Pl ace b o ...................................................................................................................................... 3 6
6. 1. 3
St u d y Pr o d uct Descri pti o n ...................................................................................................... 3 7
6. 1. 4
S u bject I de ntific ati o n N u m ber ( SI N) ..................................................................................... 3 7
6. 1. 5
Met h o d of Tre at me nt Assi g n me nt .......................................................................................... 3 7
6. 1. 6
Kit N u m ber/ R a n d o miz ati o n N u m ber .................................................................................... 3 8
6. 1. 7
I nstr ucti o ns f or Use a n d A d mi nistr ati o n ............................................................................... 3 8
6. 1. 7. 1
Tre at me nt Pr oce d ure ......................................................................................................... 3 8
6. 1. 7. 2 
P ost- tre at me nt C are ........................................................................................................... 3 9
6. 1. 7. 3
Tre at me nt Re gi me n ............................................................................................................ 4 0
6. 2
St u d y Pr o d uct P ac k a gi n g a n d L a beli n g ...................................................................................... 4 0
6. 3
S u p plies M a n a ge me nt ................................................................................................................... 4 0
6. 3. 1
Acc o u nt a bilit y .......................................................................................................................... 4 0
6. 3. 2
St or a ge of St u d y Pr o d ucts ....................................................................................................... 4 0
6. 3. 3
Dis pe nsi n g a n d Ret ur n ............................................................................................................ 4 0
6. 3. 4
Tre at me nt C o m pli a nce M a n a ge me nt a n d Rec or d ................................................................ 4 1
6. 3. 5
D ose M o dific ati o n .................................................................................................................... 4 1
6. 3. 6
Pr o d uct Q u alit y C o m pl ai nts ................................................................................................... 4 1
6. 4
Bli n di n g .......................................................................................................................................... 4 1
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 5 of 8 7
6. 4. 1
Verific ati o n of Bli n di n g ........................................................................................................... 4 2
6. 4. 2
U n bli n di n g D uri n g t he Cli nic al St u d y ................................................................................... 4 2
7.
C LI NI C A L S T U D Y A S S E S S M E N T ........................................................................................... 4 2
7. 1
Effic ac y Assess me nts ..................................................................................................................... 4 2
7. 1. 1
I n vesti g at or 4-p oi nt P h ot o gr a p hic Sc ale of L C L Se verit y ( L C L -I L A) ............................... 4 2
7. 1. 2
S u bject 4 -p oi nt P h ot o gr a p hic Sc ale of L C L Se verit y ( L C L -S L A) ...................................... 4 3
7. 2
S afet y Assess me nts ........................................................................................................................ 4 5
7. 2. 1
F oc use d P h ysic al E x a mi n ati o n ( F P E) .................................................................................... 4 5
7. 2. 2
Vit al Si g ns ................................................................................................................................. 4 5
7. 2. 3
Electr oc ar di o gr a m ( E C G) ....................................................................................................... 4 5
7. 2. 4
L a b or at or y S afet y Tests .......................................................................................................... 4 6
7. 2. 5
Ne utr alizi n g A nti b o d y Testi n g ................................................................................................ 4 7
7. 2. 6
A d verse E ve nts ......................................................................................................................... 4 7
7. 2. 6. 1
Defi niti o ns ............................................................................................................................ 4 7
7. 2. 6. 1. 1
A dverse Eve nts ( A E) ........................................................................................................ 4 7
7. 2. 6. 1. 2
Tre at me nt E mer ge nt A dverse Eve nt ( T E A E) ................................................................... 4 8
7. 2. 6. 1. 3
Seri o us A dverse Eve nts ( S A E) ......................................................................................... 4 8
7. 2. 6. 1. 4
U nex pecte d A dverse Dr u g Re acti o n ................................................................................ 4 9
7. 2. 6. 1. 5
A dverse Eve nt Re p orti n g Peri o d ..................................................................................... 4 9
7. 2. 6. 1. 6
Severity ............................................................................................................................ 4 9
7. 2. 6. 1. 7
Rel ati o ns hi p t o t he St u dy Pr o d uct a n d/ or Cli nic al St u dy Pr oce d ure .............................. 5 0
7. 2. 6. 2
Re p orti n g Pr oce d ures ......................................................................................................... 5 0
7. 2. 6. 2. 1
Pr oce d ures f or Re p orti n g A dverse Eve nts ....................................................................... 5 0
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 6 of 8 7
7. 2. 6. 2. 2
Pr oce d ure f or Re p orti n g a Seri o us A dverse Eve nt .......................................................... 5 1
7. 2. 6. 2. 3
Pr oce d ures f or Re p orti n g Pre g n a ncies ........................................................................... 5 2
7. 3
Ot her Assess me nts ........................................................................................................................ 5 3
7. 3. 1
P h ot o gr a p h y ............................................................................................................................. 5 3
7. 3. 2
Pre g n a nc y Test......................................................................................................................... 5 3
7. 4
A p pr o pri ate ness of Me as ure me nts ..............................................................................................5 3
8.
C LI NI C A L S T U D Y VI SI T S D E S C RI P TI O N S A N D P R O C E D U R E S ................................... 5 4
8. 1
Descri pti o n of Cli nic al St u d y Visits ............................................................................................. 5 4
8. 1. 1
Scree ni n g/ Visit 1 ( -1 4 d a ys t o D a y 0) ...................................................................................... 5 4
8. 1. 2
B aseli ne/ Visit 2 [ D a y 0] ............................................................................................................ 5 5
8. 1. 3
D a y 7/ Visit 3 ( ± 1 d a y) .............................................................................................................. 5 6
8. 1. 4
D a y 1 4/ Visit 4 ( ± 3 d a ys) ........................................................................................................... 5 7
8. 1. 5
M o nt h 1/ Visit 5 ( ± 5 d a ys)
........................................................................................................ 5 8
8. 1. 6
M o nt hs 2 -5/ Visit 6 -9 ( ± 5 d a ys) ................................................................................................ 5 9
8. 1. 7
M o nt h 6/ Visit 1 0 or E arl y Ter mi n ati o n visit ( ± 5 d a ys)
........................................................ 5 9
8. 2
U nsc he d ule d Visits ........................................................................................................................ 6 0
8. 3
S u bject I nstr ucti o ns ...................................................................................................................... 6 0
9.
S T A TI S TI C A L M E T H O D S P L A N N E D .................................................................................... 6 1
9. 1
St atistic al a n d A n al ytic al Pl a ns ................................................................................................... 6 1
9. 1. 1
D at a Tr a nsf or m ati o ns ............................................................................................................. 6 1
9. 1. 2
P o p ul ati o ns A n al yze d a n d E v al u a bilit y ................................................................................. 6 1
9. 1. 2. 1
M o difie d I nte nt -t o-tre at ( mI T T) Effic ac y P o p ul ati o n..................................................... 6 1
9. 1. 2. 2
I nte nt-t o-tre at (I T T) Effic ac y P o p ul ati o n......................................................................... 6 1
9. 1. 2. 3
Per -pr ot oc ol ( P P) Effic ac y P o p ul ati o n .............................................................................. 6 1
9. 1. 2. 4
S afet y P o p ul ati o n ................................................................................................................ 6 2
9. 1. 2. 5
I m p ut ati o n of Missi n g D at a ...............................................................................................6 2
9. 1. 3
D at a Prese nt ati o n a n d Gr a p hics ............................................................................................. 6 2
9. 1. 3. 1
S u b gr o u p A n al ysis .............................................................................................................. 6 2
9. 1. 3. 2
S afet y A n al ysis .................................................................................................................... 6 3
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 7 of 8 7
9. 1. 4
Wit h dr a w als a n d De vi ati o ns
................................................................................................... 6 3
9. 1. 5
I nfere nti al St atistic al A n al yses ...............................................................................................6 3
9. 2
S a m ple Size Deter mi n ati o n .......................................................................................................... 6 4
9. 2. 3
S a m ple Size C alc ul ati o n .......................................................................................................... 6 5
9. 2. 4
I nteri m A n al ysis ....................................................................................................................... 6 5
1 0.
T R AI NI N G / M O NI T O RI N G / D A T A M A N A G E M E N T / Q U A LI T Y 
A S S U R A N C E ................................................................................................................................ 6 5
1 0. 1
Pers o n nel Tr ai ni n g ........................................................................................................................ 6 5
1 0. 2
Cli ni c al M o nit ori n g ....................................................................................................................... 6 6
1 0. 3
D at a M a n a ge me nt ......................................................................................................................... 6 6
1 0. 4
Q u alit y Ass ur a nce/ A u dit/I ns pecti o n ........................................................................................... 6 6
1 0. 5
C h a n ges i n Cli nic al St u d y C o n d uct/ A me n d me nts ..................................................................... 6 7
1 0. 5. 1
Cli nic al St u d y C o n d uct ............................................................................................................ 6 7
1 0. 5. 2
A me n d me nts ............................................................................................................................. 6 7
1 1.
E T HI C S A N D G E N E R A L C LI NI C A L S T U D Y C O N D U C T C O N SI D E R A TI O N S ............. 6 7
1 1. 1
I n de pe n de nt Et hics C o m mittee (I E C) or I nstit uti o n al Re vie w B o ar d (I R B) .......................... 6 7
1 1. 2
Et hic al C o n d uct of t he Cli nic al St u d y ......................................................................................... 6 7
1 1. 3
S u bject I nf or m ati o n a n d C o nse nt ...............................................................................................6 8
1 1. 4
Pr otecti o n of Pers o n al D at a ......................................................................................................... 6 8
1 1. 5
C o ntr act u al Re q uire me nts ........................................................................................................... 6 9
1 1. 6
D at a C ollecti o n a n d Arc hi vi n g ..................................................................................................... 6 9
1 1. 6. 1
D at a C ollecti o n ......................................................................................................................... 6 9
1 1. 6. 2
S o urce D oc u me nt ati o n ............................................................................................................. 6 9
1 1. 6. 3
Arc hi ves .................................................................................................................................... 6 9
1 1. 7
I ns ur a nce ....................................................................................................................................... 7 0
1 1. 8
P u blic ati o n P olic y .......................................................................................................................... 7 0
1 1. 9
I n vesti g at or a n d A d mi nistr ati ve Str uct ure ................................................................................ 7 1
1 2.
S u m m ar y of C h a n ges i n Cli nic al St u d y Pr ot oc ol 4 3 Q M 1 9 0 1 ........................................................ 7 2
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 8 of 8 7
1 2. 1
Pr ot oc ol Versi o n 3. 0 t o Versi o n 4. 0 ............................................................................................. 7 2
1 3.
LI T E R A T U R E R E F E R E N C E LI S T ................................................................................................ 7 4
1 4.
A P P E N DI C E S .................................................................................................................................... 7 5
A p pe n di x 1
V ali d at e d I n vesti g at or 4 -p oi nt P h ot o gr a p hic Sc ale of L ater al C a nt h al Li ne 
Se verit y ( L C L -I L A) ...................................................................................................................... 7 5
A p pe n di x 2
V ali d ate d S u bject 4 -p oi nt P h ot o gr a p hic Sc ale of L ater al C a nt h al Li ne 
Se verit y ( L C L -S L A) ...................................................................................................................... 7 7
A p pe n di x 6
F oc use d P h ysic al E x a mi n ati o n F or m E x a m ple ................................................................ 8 4
A p pe n di x 7
A d verse E ve nts P ote nti all y S u g gesti ve of Re m ote S pre a d of T o xi n ............................... 8 6
SI G N E D A G R E E M E N T O F T H E C LI NI C A L S T U D Y P R O T O C O L .................................................. 8 7
List of T a bles
Ta ble 1
Cli nical St u d y Sc he matic ........................................................................................................... 1 6
Ta ble 2
Sc he d ule of Assess me nts ........................................................................................................... 1 8
Ta ble 3
Descri pti o n a n d Usa ge of t he St u d y Pr o d ucts ............................................................................ 3 7
List of Fi g ures
Fi g ure 1 
St u d y Fl o w C hart ....................................................................................................................... 1 7
Fi g ure 2
I njecti o n Sites f or Treati n g L C L O pti o n 1 ................................................................................. 3 9
Fi g ure 3
I njecti o n Sites f or Treati n g L C L O pti o n 2 ................................................................................. 3 9
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 9 of 8 7
S Y N O P SI S
Cli ni c al St u d y  Titl e: A M ulti c e nt er, R a n d o mi z e d, D o u bl e- Bli n d, Pl a c e b o -C o ntr oll e d St u d y t o E v al u at e t h e Effi c a c y 
a n d S af et y of Q M 1 1 1 4 -D P f or t h e Tr e at m e nt of M o d er at e t o S e v er e L at er al C a nt h al Li n e s (R E A D Y – 2)
S h ort Titl e: Q M 1 1 1 4 -D P L at er al C a nt h al Li n e s
Cli ni c al St u d y  P o p ul ati o n:
M al e a n d f e m al e s u bj e ct s, 1 8 y e ar s of a g e a n d ol d er, wit h m o d er at e t o 
s e v er e l at er al c a nt h al li n e s ( L C L ) at m a xi m u m s mil e.
Cli ni c al St u d y  D e si g n:
T hi s i s a p h a s e 3, m ulti -c e nt er, r a n d o mi z e d, d o u bl e bli n d, pl a c e b o-
c o ntr oll e d st u d y t o e v al u at e t h e effi c a c y a n d s af et y of 6 0 u nit s ( U) of 
Q M 1 1 1 4 -D P f or t h e tr e at m e nt of m o d er at e t o s e v er e L C L. 
F oll o wi n g t h e i nf or m e d c o n s e nt a n d t h e s cr e e ni n g pr o c e s s, eli gi bl e s u bj e ct s 
will b e r a n d o ml y a s si g n e d i n a 3: 1 r ati o t o r e c ei v e a si n gl e tr e at m e nt at 
b a s eli n e of 6 0 u nit s Q M 1 1 1 4 -D P ( 2 2 5 s u bj e ct s) or pl a c e b o ( 7 5 s u bj e ct s) i n 
t h e L C L ar e a s . R a n d o mi z ati o n will b e str atifi e d b y st u d y c e nt er. 
E a c h s u bj e ct will r e c ei v e a si n gl e tr e at m e nt di vi d e d e q u all y a m o n g 6
i nj e cti o n p oi nt s ( 0. 1 m L p er i nj e cti o n p oi nt) i n t h e L C L r e gi o n.   
F oll o wi n g tr e at m e nt at b a s eli n e, s u bj e ct s will b e m o nit or e d f or s af et y a n d 
effi c a c y f or 6 m o nt h s.
T ar g et I n di c ati o n:
T hi s st u d y i s d e si g n e d t o e v al u at e t h e s af et y a n d effi c a c y of Q M 1 1 1 4 -D P 
f or t h e tr e at m e nt of m o d er at e t o s e v er e L C L.
T ot al N u m b er of S u bj e ct s ( Pl a n n e d): 
A p pr o xi m at el y 3 0 0 s u bj e ct s will b e e nr oll e d.
N u m b er of C li ni c al S t u d y C e nt er s 
( Pl a n n e d):
U p t o 1 5 c e nt er s
R e gi o n( s) / C o u ntr y (i e s) In v ol v e d 
( Pl a n n e d):
U S a n d C a n a d a
Cli ni c al S t u d y D ur ati o n:
T h e pl a n n e d d ur ati o n of r e cr uit m e nt (fr o m fir st s u bj e ct fir st vi sit [ F S F V] t o 
l a st s u bj e ct fir st vi sit [ L S F V]) i s a p pr o xi m at el y 3 m o nt h s.
T h e pl a n n e d cli ni c al st u d y d ur ati o n fr o m F S F V t o l a st s u bj e ct l a st vi sit 
(L S L V) i s a p pr o xi m at el y 9 . 5 m o nt h s.
D ur ati o n of S u bj e ct P arti ci p ati o n: 
Cli ni c al st u d y p arti ci p ati o n f or e a c h s u bj e ct i s a p pr o xi m at el y 6 . 5 m o nt h s.
K e y I n cl u si o n C rit eri a:
1.
M al e or f e m al e 1 8 y e ar s of a g e
or ol d er .
2.
M o d er at e t o s e v er e bil at er all y s y m m etri c al L C L ( gr a d e 2 or 3 o n t h e 4-
p oi nt P h ot o gr a p hi c S c al e r a n gi n g fr o m 0 [ n o n e] t o 3 [ s e v er e]) at 
m a xi m u m s mil e a s a s s e s s e d b y t h e I n v e sti g at or li v e a s s e s s m e nt 
( L C L-I L A).
3.
B il at er all y s y m m etri c al L C L gr a d e d a s L e v el 2 or L e v el 3 o n t h e 4- p oi nt 
P h ot o gr a p hi c S c al e (r a n gi n g fr o m L e v el 0 t o L e v el 3) at m a xi m u m 
s mil e a s a s s e s s e d b y t h e s u bj e ct li v e a s s e s s m e nt ( L C L -S L A).
4.
F e m al e of n o n -c hil d b e ari n g p ot e nti al (i. e., p o st -m e n o p a u s al [ a b s e n c e 
of m e n str u al bl e e di n g f or 1 y e ar pri or t o s cr e e ni n g, wit h o ut a n y ot h er 
m e di c al 
r e a s o n], or 
h a s 
u n d er g o n e 
h y st er e ct o m y 
or 
bil at er al 
o o p h or e ct o m y).
O R
F e m al e of c hil d b e ari n g p ot e nti al wit h a n e g ati v e uri n e pr e g n a n c y t e st 
at s cr e e ni n g a n d b a s eli n e, a n d a gr e e s t o u s e a hi g hl y eff e cti v e a n d 
a p pr o v e d c o ntr a c e pti v e m et h o d f or t h e d ur ati o n of t h e st u d y. A hi g hl y 
eff e cti v e m et h o d of c o ntr a c e pti o n i s d efi n e d a s:

Bil at er al t u b al li g ati o n;
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 1 0 of 8 7
S Y N O P SI S
Cli ni c al St u d y  Titl e: A M ulti c e nt er, R a n d o mi z e d, D o u bl e- Bli n d, Pl a c e b o -C o ntr oll e d St u d y t o E v al u at e t h e Effi c a c y 
a n d S af et y of Q M 1 1 1 4 -D P f or t h e Tr e at m e nt of M o d er at e t o S e v er e L at er al C a nt h al Li n e s (R E A D Y – 2)

C o m bi n e d 
( e str o g e n a n d 
pr o g e st er o n e 
c o nt ai ni n g) 
or al, 
i ntr a v a gi n al or tr a n s d er m al c o ntr a c e pti v e s t h at i n hi bit o v ul ati o n 
a s t h e pri m ar y m o d e of a cti o n, o n a st a bl e d o s e f or at l e a st 2 8 
d a y s pri or t o s cr e e ni n g vi sit;

I ntr a ut eri n e d e vi c e (I U D) i n s ert e d at l e a st 2 8 d a y s pri or t o 
s cr e e ni n g vi sit; 

I ntr a ut eri n e h or m o n e-r el e a si n g s y st e m;

P art n er v a s e ct o mi z e d f or at l e a st t hr e e m o nt h s pri or t o s cr e e ni n g 
vi sit;

Pr o g e st o g e n -o nl y or al , i nj e ct a bl e or i m pl a nt a bl e c o ntr a c e pti v e s 
t h at i n hi bit o v ul ati o n a s t h e pri m ar y m o d e of a cti o n, o n a st a bl e 
d o s e f or at l e a st 2 8 d a y s pri or t o s cr e e ni n g vi sit; or

Stri ct a b sti n e n c e (i. e., r efr ai ni n g fr o m h et er o s e x u al i nt er c o ur s e 
f or t h e e ntir e d ur ati o n of t h e s u bj e ct' s p arti ci p ati o n i n t h e st u d y).
5.
Ti m e a n d a bilit y t o c o m pl et e t h e st u d y a n d c o m pl y wit h i n str u cti o n s.
6.
U n d er st a n d s t h e st u d y r e q uir e m e nt s a n d si g n e d t h e i nf or m e d c o n s e nt 
f or m (I C F).
K e y E x cl u si o n C rit eri a:
1.
Pr e vi o u s u s e of a n y B ot uli n u m t o xi n tr e at m e nt i n f a ci al ar e a s wit hi n 9 
m o nt h s pri or t o st u d y tr e at m e nt.
2.
A nti ci p at e d n e e d f or tr e at m e nt wit h b ot uli n u m t o xi n of a n y s er ot y p e f or 
a n y r e a s o n d uri n g t h e st u d y ( ot h er t h a n t h e i n v e sti g ati o n al pr o d u ct).
3.
F e m al e w h o i s pr e g n a nt, br e a st f e e di n g, or i nt e n d s t o c o n c ei v e a c hil d 
d uri n g t h e st u d y.
4.
K n o w n 
all er g y 
or 
h y p er s e n siti vit y 
t o a n y 
c o m p o n e nt 
of 
t h e 
i n v e sti g ati o n al pr o d u ct ( Q M 1 1 1 4 -D P) or a n y b ot uli n u m t o xi n s er ot y p e .
5.
I n a bilit y t o s u b st a nti all y r e d u c e t h e a p p e ar a n c e of f a ci al r h yti d e s i n t h e 
tr e at m e nt ar e a b y p h y si c all y s pr e a di n g t h e m a p art, a s d et er mi n e d b y 
t h e i n v e sti g at or.
6.
Cli ni c all y si g nifi c a nt a b n or m al f o c u s e d p h y si c al e x a mi n ati o n fi n di n g( s) 
at s cr e e ni n g or b a s eli n e vi sit s , i n t h e i n v e sti g at or’ s o pi ni o n.
7.
E x c e s si v e s ki n l a xit y i n t h e tr e at m e nt ar ea or p eri or bit al ar e a.
8.
Pr e vi o u s u s e of a n y h y al ur o ni c a ci d s oft ti s s u e a u g m e nt ati o n t h er a p y 
i n t h e l at er al c a nt h al ar e a wit hi n 6 m o nt h s b ef or e b a s eli n e .
9.
Pr e vi o u s 
s oft ti s s u e a u g m e nt ati o n 
wit h 
a n y 
p er m a n e nt 
( n o n-
bi o d e gr a d a bl e s u c h a s sili c o n e, p ol y a cr yl a mi d e, et c )
or s e mi -
p er m a n e nt 
(i. e. c al ci u m 
h y dr o x yl a p atit e, 
p ol y - L-L a cti c 
a ci d 
or 
p ol y m et h yl -m et h a cr yl at e) pr o d u ct; lifti n g t hr e a d s, or a ut ol o g o u s f at i n 
t h e tr e at m ent ar e a. 
1 0.
Hi st or y, pr e s e n c e or pr e di s p o siti o n of e y eli d or e y e br o w pt o si s ( h e a v y 
e y e br o w s), a m bl y o pi a (i. e., l a z y e y e), or pr e vi o u s s ur g er y ar o u n d t h e 
e y e t h at m a y 
l e a d t o t h e a b o v e e v e nt s, a s d et er mi n e d b y t h e 
In v e sti g at or .
1 1.
M ar k e d f a ci al a s y m m etr y, e x c e s s i v e d er m at o c h al a si s (i. e., e x c e s s of 
s ki n i n e y eli d s), or m ar k e d p eri o c ul ar or e y e br o w a s y m m etr y .
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 1 1 of 8 7
S Y N O P SI S
Cli ni c al St u d y  Titl e: A M ulti c e nt er, R a n d o mi z e d, D o u bl e- Bli n d, Pl a c e b o -C o ntr oll e d St u d y t o E v al u at e t h e Effi c a c y 
a n d S af et y of Q M 1 1 1 4 -D P f or t h e Tr e at m e nt of M o d er at e t o S e v er e L at er al C a nt h al Li n e s (R E A D Y – 2)
1 2.
Pr e s e n c e of s c ar( s) , pi er ci n g( s), or t att o o s (i n cl u di n g mi cr o bl a di n g of 
e y e br o w or e y eli n er) i n t h e tr e at m e nt ar e a or ar o u n d t h e tr e at m e nt 
ar e a, t h at i n t h e In v e sti g at or' s o pi ni o n , m a y 
i nt erf er e wit h st u d y 
e v al u ati o n s. 
1 3.
Pr e s e n c e of i nfl a m m ati o n, a cti v e i nf e cti o n or s ki n di s or d er, s u c h a s 
e c z e m a, r o s a c e a, f a ci al p s ori a si s, h er p e s z o st er et c ., n e ar or i n t h e 
tr e at m e nt ar e a.
1 4.
P r e s e n c e of c a n c er o u s or pr e -c a n c er o u s l e si o n s i n t h e tr e at m e nt ar e a. 
1 5.
Hi st or y of ot h er f a ci al tr e at m e nt, s ur g er y, or ot h er a e st h eti c pr o c e d ur e s 
( e. g. a bl ati v e s ki n r e s urf a ci n g, l a s er tr e at m e nt, mi cr o n e e dli n g, 
or 
c h e mi c al p e el ) i n t h e pr e vi o u s 1 2 m o nt h s t h at, i n t h e I n v e sti g at or’ s 
o pi ni o n , c o ul d i nt erf er e wit h st u d y i nj e cti o n s a n d/ or a s s e s s m e nt s or 
e x p o s e t h e s u bj e ct t o u n d u e ri s k b y st u d y p arti ci p ati o n .
1 6.
Pl a n n e d f a ci al s ur g er y, e y e s ur g er y (i n cl u di n g L A SI K pr o c e d ur e) or 
a e st h eti c pr o c e d ur e s ( e. g. a bl ati v e s k i n r e s urf a ci n g, l a s er tr e at m e nt, 
mi cr o n e e dli n g, or c h e mi c al p e el i n t h e u p p er or mi df a ci al ar e a) d uri n g 
t h e st u d y p eri o d.
1 7.
Hi st or y or pr e s e n c e of f a ci al n er v e p al s y, or a n y m e di c al c o n diti o n t h at 
m a y p ut t h e s u bj e ct at i n cr e a s e d ri s k wit h e x p o s ur e t o b ot uli n u m t o xi n 
i n cl u di n g di a g n o s e d m y a st h e ni a 
gr a vi s, L a m b ert -E at o n s y n dr o m e, 
a m y otr o p hi c l at er al s cl er o si s, or a n y ot h er c o n diti o n t h at mi g ht 
i nt erf er e wit h n e ur o m u s c ul ar fu n cti o n. 
1 8.
U s e of m e di c ati o n s t h at aff e ct n e ur o m u s c ul ar tr a n s mi s si o n s u c h a s 
c ur ar e -li k e 
d e p ol ari zi n g 
a g e nt s, 
li n c o s a mi d e s, 
p ol y m y xi n s, 
a nti c h oli n e st er a s e s, a n d a mi n o gl y c o si d e a nti bi oti c s.
1 9.
S u bj e ct 
wit h
bl e e di n g 
di s or d er 
or 
s u bj e ct 
c urr e ntl y 
u si n g 
a nti c o a g ul a nt s.
2 0.
S u b j e ct h a s a n y pri or or c urr e nt p s y c hi atri c ill n e s s ( e. g. p s y c h o si s, 
d e pr e s si o n, 
a n xi et y), 
al c o h ol 
or 
dr u g 
a b u s e, 
or 
i s t a ki n g 
a nti d e pr e s s a nt, a n xi ol yti c, or a nti p s y c h oti c m e di c ati o n 
t h at, i n t h e 
I n v e sti g at or' s o pi ni o n, c o ul d aff e ct t h e s u bj e ct' s s a f et y a n d/ or t h e 
c o n d u ct or o ut c o m e of t h e st u d y.
2 1.
Ot h er c o n c urr e nt m e di c al c o n diti o n s, t h er a p y or ot h er c o n diti o n t h at i n 
t h e I n v e sti g at or' s o pi ni o n w o ul d i nt erf er e wit h t h e e v al u ati o n of t h e 
st u d y m e di c ati o n s af et y or effi c a c y a n d/ or p ut t h e s u bj e ct at ri sk if 
h e/ s h e p arti ci p at e s t o t h e st u d y.
2 2.
P arti ci p ati o n i n a n i n v e sti g ati o n al d e vi c e or dr u g st u d y wit hi n 3 0 d a y s 
pri or t o st u d y tr e at m e nt or pl a n s t o e nr oll i n a n y ot h er i n v e sti g ati o n al 
st u d y d uri n g p arti ci p ati o n i n t hi s st u d y.
2 3.
St u d y c e nt er p er s o n n el, cl o s e r el ati v e s of t h e st u d y c e nt er p er s o n n el 
( e. g. p ar e nt s, c hil dr e n, si bli n g s, or s p o u s e), e m pl o y e e s or cl o s e 
r el ati v e s of e m pl o y e e s at t h e S p o n s or c o m p a n y.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 1 2 of 8 7
S Y N O P SI S
Cli ni c al St u d y  Titl e: A M ulti c e nt er, R a n d o mi z e d, D o u bl e- Bli n d, Pl a c e b o -C o ntr oll e d St u d y t o E v al u at e t h e Effi c a c y 
a n d S af et y of Q M 1 1 1 4 -D P f or t h e Tr e at m e nt of M o d er at e t o S e v er e L at er al C a nt h al Li n e s (R E A D Y – 2)
I n v e sti g ati o n al P r o d u ct:
Q M 1 1 1 4 -D P , b uff er e d s ol uti o n f or i nj e cti o n
Str e n gt h/ C o n c e ntr ati o n:
1 0 0 U/ m L
D o s a g e (t ot al d ail y  d o s e):
6 0 U t ot al (0. 6 m L t ot al/ 0. 3 m L p er tr e at m e nt si d e)
1 0 U p er i nj e cti o n p oi nt ( 0. 1
m L p er i nj e cti o n p oi nt)
R o ut e:
I ntr a m u s c ul ar i nj e cti o n
D o s e r e gi m e n:
Si n gl e tr e at m e nt at b a s eli n e vi sit
L o c ati o n of tr e at e d ar e a:
L at er al c a nt h u s ar e a s
Pl a c e b o Pr o d u ct:
Pl a c e b o , b uff er e d s ol uti o n f or i nj e cti o n
Str e n gt h/ C o n c e ntr ati o n:
N/ A
D o s a g e (t ot al d ail y  d o s e):
0. 6 m L t ot al /0. 3 m L p er tr e at m e nt si d e
0. 1 m L p er i nj e cti o n p oi nt
R o ut e:
I ntr a m u s c ul ar i nj e cti o n
D o s e r e gi m e n:
Si n gl e tr e at m e nt at b a s eli n e vi sit
L o c ati o n of tr e at e d ar e a:
L at er al c a nt h u s ar e a s
Effi c a c y  As s e s s m e nt:

I n v e sti g at or 4- p oi nt P h ot o gr a p hi c S c al e of L C L S e v erit y at 
 
 m a xi m u m s mil e (I n v e sti g at or a s s e s s m e nt [ L C L-I L A])

S u bj e ct 4- p oi nt P h ot o gr a p hi c S c al e of L C L S e v erit y at 
 
 m a xi m u m s mil e ( s u bj e ct a s s e s s m e nt [ L C L-S L A] )
St u d y  O bj e cti v e:
T h e o bj e cti v e of t h e st u d y i s t o e v al u at e t h e effi c a c y a n d s af et y of a si n gl e 
d o s e of 6 0 U of Q M 1 1 1 4 -D P c o m p ar e d t o pl a c e b o f or t h e tr e at m e nt of 
m o d er at e t o s e v er e L C L .
Pri m ar y  Effi c a cy O bj e cti v e a n d 
E n d p oi nt:
T h e pri m ar y effi c a c y o bj e cti v e :
To e v al u at e a si n gl e d o s e of 6 0 U of 
Q M 1 1 1 4 -D P c o m p ar e d t o pl a c e b o f or t h e tr e at m e nt of m o d er at e t o s e v er e 
L C L .
F or t h e pri m ar y e n d p oi nt, t h e c o m p o sit e r e s p o n d er r at e will b e e v al u at e d at 
M o nt h 1 u si n g t h e L C L -I LA a n d t h e L C L - S L A at m a xi m u m s mil e.
A c o m p o sit e r e s p o n d er i s d efi n e d a s a s u bj e ct w h o a c hi e v e s gr a d e/l e v el 0 
or 1 i n L C L s e v erit y a n d at l e a st 2 gr a d e s /l e v el s i m pr o v e m e nt fr o m b a s eli n e 
o n b ot h t h e L C L -I L A a n d L C L-S L A s c al e s c o n c urr e ntl y.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 1 3 of 8 7
S Y N O P SI S
Cli ni c al St u d y  Titl e: A M ulti c e nt er, R a n d o mi z e d, D o u bl e- Bli n d, Pl a c e b o -C o ntr oll e d St u d y t o E v al u at e t h e Effi c a c y 
a n d S af et y of Q M 1 1 1 4 -D P f or t h e Tr e at m e nt of M o d er at e t o S e v er e L at er al C a nt h al Li n e s (R E A D Y – 2)
S e c o n d ar y  Effi c a c y O bj e cti v e s a n d 
E n d p oi nt s:
S e c o n d ar y o bj e cti v e: T o e v al u at e t h e effi c a c y of a si n gl e d o s e of 6 0 U of 
Q M 1 1 1 4 -D P c o m p ar e d t o pl a c e b o f or t h e tr e at m e nt of m o d er at e t o s e v er e 
L C L .
E n d p oi nt: 
P er c e nt a g e of s u bj e ct s w h o a c hi e v e gr a d e 0 or 1 at :

M o nt h 1 u si n g L C L -I L A at m a xi m u m s mil e .

E a c h p o st -tr e at m e nt vi sit ( e x cl u di n g M o nt h 
1) u si n g L C L -I L A at 
m a xi m u m s mil e.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 1 4 of 8 7
S Y N O P SI S
Cli ni c al St u d y  Titl e: A M ulti c e nt er, R a n d o mi z e d, D o u bl e- Bli n d, Pl a c e b o -C o ntr oll e d St u d y t o E v al u at e t h e Effi c a c y 
a n d S af et y of Q M 1 1 1 4 -D P f or t h e Tr e at m e nt of M o d er at e t o S e v er e L at er al C a nt h al Li n e s (R E A D Y – 2)
S af et y  As s e s s m e nt:

A d v er s e e v e nt s ( A E s)

F o c u s e d p h y si c al e x a mi n ati o n ( F P E)

Vit al si g n s

El e ctr o c ar di o gr a m ( E C G)

L a b or at or y s af et y t e st s ( c h e mi str y a n d h e m at ol o g y)

Pr o d u cti o n of n e utr ali zi n g a nti b o di e s a g ai n st Q M 1 1 1 4 -D P
S af et y  O bj e cti v es a n d E n d p oi nt s:
T o e v al u at e t h e s af et y of a si n gl e d o s e of 6 0 U of Q M 1 1 1 4 -D P c o m p ar e d 
t o pl a c e b o f or t h e tr e at m e nt of m o d er at e t o s e v er e L C L.
E n d p oi nt s:

I n ci d e n c e a n d s e v erit y of tr e at m e nt e m er g e nt A E s ( T E A E s)

F P E fi n di n g s 

Vit al si g n s

E C G

L a b or at or y p ar a m et er s ( cli ni c al c h e mi str y a n d h e m at ol o g y)

N e utr ali zi n g a nti b o d y pr o d u cti o n
Ot h er A s s e s s m e nt s: 

P h ot o gr a p h y

Pr e g n a n c y t e st
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 1 5 of 8 7
S Y N O P SI S
Cli ni c al St u d y  Titl e: A M ulti c e nt er, R a n d o mi z e d, D o u bl e- Bli n d, Pl a c e b o -C o ntr oll e d St u d y t o E v al u at e t h e Effi c a c y 
a n d S af et y of Q M 1 1 1 4 -D P f or t h e Tr e at m e nt of M o d er at e t o S e v er e L at er al C a nt h al Li n e s (R E A D Y – 2)
Bli n di n g:
T hi s i s a d o u bl e -bli n d st u d y i n w hi c h 
n eit h er t h e I n v e sti g at or, s u b -
I n v e sti g at or, st u d y st aff, n or t h e s u bj e ct will k n o w t h e s u bj e ct' s st u d y 
pr o d u ct a s si g n m e nt (i. e., Q M 1 1 1 4 -D P or pl a c e b o). Pl a c e b o i s i d e nti c al i n 
a p p e ar a n c e t o Q M 1 1 1 4 -D P b ut c o nt ai n s n o a cti v e dr u g s u b st a n c e.
S u bj e ct s will b e r a n d o mi z e d at b a s eli n e t o eit h er tr e at m e nt wit h Q M 1 1 1 4 -
D P or pl a c e b o. I n or d er t o m ai nt ai n t h e bli n d, t h e st u d y pr o d u ct s, Q M 1 1 1 4 -
D P a n d pl a c e b o, will b e s u p pli e d i n i d e nti c al vi al s, e a c h wit h a u ni q u e 
n u m b er o n t h e vi al l a b el. B ot h Q M 1 1 1 4 -D P 
a n d pl a c e b o will 
b e 
a d mi ni st er e d i n e x a ctl y t h e s a m e w a y.
Pri n ci p al St ati sti c al M et h o d:
T h e pri m ar y effi c a c y e n d p oi nt will b e a c o m p o sit e r e s p o n d er r at e b a s e d o n 
t h e I L A a n d S L A of L C L s e v erit y at m a xi m u m s mil e at M o nt h 1. A r e s p o n d er 
i s d efi n e d a s a s u bj e ct w h o a c hi e v e s gr a d e/l e v el 0 or 1 a n d at l e a st 2 gr a d e s 
i m pr o v e m e nt fr o m b a s eli n e o n b ot h s c al e s c o n c urr e ntl y. T h e r e s p o n d er 
r at e s of t h e Q M 1 1 1 4 -D P a n d pl a c e b o will b e c o m p ar e d u si n g C o c hr a n -
M a nt el -H a e n s z el t est (str atifi e d b y c e nt er) at 5 % si g nifi c a n c e l e v el ( 2-
si d e d). 
S e c o n d ar y e n d p oi nt s will b e a n al y z e d u si n g t h e C o c hr a n -M a nt el -H a e n s z el
t e st ( str atifi e d b y c e nt er). T h e fi x e d s e q u e n c e t e sti n g pr o c e d ur e will b e u s e d 
t o c o ntr ol t h e t y p e I err or r at e f or t h e m ulti pl e t e sti n g.
 s af et y e n d p oi nt s, will b e a n al y z e d 
d e s cri pti v el y a s a p pr o pri at e . P- v al u e s mi g ht b e pr o vi d e d f or d e s cri pti v e 
p ur p o s e s. P er c e nt a g e s of s u bj e ct s o v er ti m e will b e pr e s e nt e d i n gr a p h s. 
D ur ati o n of eff e ct a n d ti m e t o o n s et will b e a n al y z e d wit h K a pl a n -M ei er 
m et h o d s .
S a m pl e Si z e:
T h e st u d y i s pl a n n e d t o e nr oll a p pr o xi m at el y 3 0 0 s u bj e ct s w h o will b e 
tr e at e d wit h eit h er 6 0 u nit s of Q M 1 1 1 4 -D P (2 2 5 s u bj e ct s) or pl a c e b o (7 5
s u bj e ct s). T h e s a m pl e si z e i s d et er mi n e d b y t h e n u m b er of s u bj e ct s 
e x p o s e d t o Q M 1 1 1 4 - D P i n t h e L C L a n d a m o u nt of l o n g-t er m s af et y d at a.
I nt eri m A n al ysi s (I A):
N ot a p pli c a bl e.  A n i nt eri m a n al y si s i s n ot pl a n n e d f or t hi s st u d y. 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI

C O N FI D E N TI A L
Pa ge 1 6 of 8 7
C LI N I CA L S T U D Y S C H E M A TI C A N D F L O W C H A R T
T a ble 1  
Cli nic al St u d y Sc he m atic
                                   S cr e e ni n g
                                    
                                      B a s eli n e/ R a n d o mi z ati o n t o Tr e at m e nt
                                     
Gr o u p 1
Gr o u p 2
n = 2 2 5
n = 7 5
Tr e at m e nt 
Q M 1 1 1 4 -D P 6 0 u nit s
Pl a c e b o
Tr e at m e nt Fr e q u e n c y
Si n gl e tr e at m e nt at b a s eli n e
Si n gl e tr e at m e nt at b a s eli n e
                                     
                                     F oll o w u p Vi sit s
                                    D a y s 7 a n d 1 4, a n d M o nt h s 1, 2, 3, 4, 5, a n d 6/ E T
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 1 7 of 8 7
Fi g ure 1
St u d y Fl o w C h art
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 1 8 of 8 7
S C H E D U L E O F A S S E S S M E N T S
T a ble 2
Sc he d ule of A ssess me nts
Defi niti o n 1 m o nt h = 4 wee ks / 2 8 da ys
All visit wi n d o ws are calc ulate d fr o m Baseli ne/ Da y 0
Visit 1
Visit 2
Visit 
3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 1 0
Scree ni n g 1
Baseli ne/ Da y 0 1
( wit hi n 2 wee ks after 
scree ni n g)
Da y 7
( ±1 da y )
Da y 1 4
(3 da ys)
M o nt h 1
(5 da y s)
M o nt h 2
(5 da y s)
M o nt h 3
(5 da y s)
M o nt h 4
(5 da y s)
M o nt h 5
(5 da y s)
M o nt h
6/ E T 2
(5 da y s)
I nf or me d C o nse nt
X
De m o gra p hic Data 3 i ncl u di n g, Fitz patric k s ki n t y pe, me dical 
hist or y 
& 
c o nc urre nt 
diseases, 
pre vi o us 
facial 
treat me nts/ pr oce d ures (t o xi n naï ve/ n o n-t o xi n naï ve)
X
I ncl usi o n / E xcl usi o n Criteria
X
X
4
C o nc o mita nt T hera pies / Pr oce d ures 
X
X
5
X  
X  
X  
X  
X  
X  
X
X
A d verse E ve nts 
X
X
5
X  
X  
X  
X  
X  
X  
X
X
Uri ne Pre g na nc y Test 6
X
X
4
X
Vital Si g ns ( bl o o d press ure, heart rate, a n d res pirat or y rate)7
X
5
X  
X  
X
X
E C G
X 4
X
X
Bl o o d sa m ple cli nical c he mistr y a n d he mat ol o g y
X 4
X
Bl o o d sa m ple f or ser u m a nti b o d y testi n g
X 4
X
X
I L A of L C L Se verit y
X
X
4
X  
X  
X  
X  
X  
X  
X
X
F oc use d P h ysical E xa mi nati o n (face, hea d, nec k) 8
X
X
4
X  
X  
X
X
P h ot o gra p h y
X
4
X  
X  
X  
X  
X  
X  
X
X
Ra n d o mizati o n
X
4
Treat me nt
X 9
S u bject assess me nts
S L A of L C L Se verit y 1 0
X
X
4
X  
X  
X  
X  
X  
X  
X
X
1. Scree ni n g a n d b aseli ne visits m ay be o n t he s a me d ay. If c o m plete d o n t he s a me d ay, o nly perf or m st u dy assess me nts 
o nce (i.e., P E, U P T, S L A, I L A, A E, c o nc o mit a nt t her a pies/ pr oce d ures, i ncl usi o n/excl usi o n revie w)
2. If t he s u bject wit h dr a ws bef ore t he fi n al visit t he assess me nts at M o nt h 6/ E T s h o ul d be c o m plete d, if p ossi ble.
3. I ncl u des d ate of birt h, ge n der, r ace, et h nicity, hei g ht, a n d wei g ht.
4. T o be perf or me d bef ore tre at me nt.
6. Fe m ales of c hil d be ari n g p ote nti al.
7.
Vit al si g ns are t ake n se ate d after 1 0 mi n utes rest. Vit al si g ns are t ake n pri or t o a n y bl o o d dr a w 
(excl u di n g p ost-tre at me nt me as ure me nts o n D ay 0).
8. 
P ost- b aseli ne, eve nts s u g gestive of re m ote s pre a d of t oxi n are als o c o nsi dere d w h ile d oi n g cli nical 
ev al u ati o ns b ase d o n t he s u bject’s sy m pt o ms a n d si g ns. Directe d q uesti o ni n g a n d ex a mi n ati o n will 
t he n be perf or me d as a p pr o pri ate.
9.
F oll o wi n g tre at me nt a d mi nistr ati o n, s u bjects will be m o nit ore d at t he st u dy ce nter f or 3 0 mi n utes.
1 0.
S u bjects will m ake t heir L ater al C a nt h al Li ne assess me nts i n de pe n de ntly of t he I nvesti g at or’s 
assess me nt.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
Versi o n :
Effecti ve  date:
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 1 9 of 8 7
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
A b brevi ati o n / Ter m
Defi niti o n
C
De grees Celsi us
A E 
A d verse E ve nt
A L P
Al kali ne P h os p hatase
A L T/ A L A T ( S G P T)
Ala ni ne A mi n otra nsferase ( Ser u m Gl uta mic P yr u vic Tra nsa mi nase)
A S T/ A S A T ( S G O T)
As partate 
A mi n otra nsferase 
( Ser u m 
Gl uta mic 
O xal oacetic 
Tra nsa mi nase)
B o N T
B ot uli n u m T o xi n
B o N T - A
B ot uli n u m T o xi n T y pe A
C F R
C o de of Fe deral Re g ulati o ns
C R O
C o ntract Researc h Or ga nizati o n
C S P
Cli nical St u d y  Pr ot oc ol
C S R
Cli nical St u d y  Re p ort
C T A
Cli nical Trial A gree me nt
C T N
Cli nical Trial N u m ber
D M P
Data Ma na ge me nt Pla n
E C G
Electr ocar di o gra m
e C R F
Electr o nic Case Re p ort F or m
E D C
Electr o nic Data Ca pt ure
e. g. 
F or E xa m ple ( Lati n: e xe m pli gratia)
E T
Earl y Ter mi nati o n
F
De grees Fa hre n heit
F D A
F o o d a n d Dr u g A d mi nistrati o n
F S F V
First S u bject First Visit (first s u bject scree ne d, i.e. w h o si g ns t he 
i nf or me d c o nse nt f or m)
F S L V
First S u bject L ast Visit
G C P 
G o o d Cli nical Practice 
G G T
Ga m ma Gl uta m yl  Tra nsferase
G L P
G o o d La b orat or y  Practices
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI

C O N FI D E N TI A L
Pa ge 2 0 of 8 7
A b brevi ati o n / Ter m
Defi niti o n
H b
Hae m o gl o bi n
Hct
He mat ocrit
HI P A A
Healt h I ns ura nce P orta bilit y  a n d Acc o u nta bilit y Act of 1 9 9 6
I B
I n vesti gat or’s Br oc h ure
I CF
I nf or me d C o nse nt F or m
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n 
i.e. 
T hat is ( Lati n: i d est)
I L A
I n vesti gat or Li ve Assess me nt
I M
I ntra m usc ular
I ND
I n vesti gati o nal Ne w Dr u g
I n vesti gat or
T he Pri nci pal I nvesti gat or ( PI) or ot her q ualifie d pers o n, i.e. s u b-
In vesti gat or, desi g nate d a n d s u per vise d b y  the PI  at a st u d y site t o 
perf or m critical st u d y -relate d pr oce d ures or t o ma ke i m p orta nt st u d y-
relate d decisi o ns as s pecifie d o n t he si g nat ure a n d dele gati o n l o g
I n vesti gat or File
Esse ntial d oc u me nts relati n g t o a cli nical st u d y as defi ne d i n 
a p plica ble G C P 
g ui da nce 
d oc u me nt 
a n d mai ntai ne d 
b y  the 
In vesti gat or.
I n vesti gati o nal Pr o d uct
A p har mace utical f or m of a n acti ve i n gre die nt bei n g teste d i n a cli nical 
st u d y, i ncl u di n g a pr o d uct wit h a mar keti n g aut h orizati o n w he n use d 
or asse m ble d (f or m ulate d or pac ka ge d) i n a wa y differe nt fr o m t he 
a p pr o ve d f or m, or w he n use d f or a n u na p pr o ve d i n dicati o n, or w he n 
use d t o gai n f urt her i nf or mati o n a b o ut a n a p pr o ve d use.
I RB
I nstit uti o nal Re vie w B oar d
I T T
I nte nti o n-t o-treat
I UD
I ntra uteri ne De vice
k Da
kil o dalt o n
K M
Ka pla n -Meier
L C L
Lateral Ca nt hal Li nes
L S F V
Last S u bject First Visit (last s u bject scree ne d, i.e. w h o si g ns t he 
i nf or me d c o nse nt f or m)
L S L V
Last S u bject Last Visit (last s u bject w h o c o m plete d its last cli nical 
st u d y visit)
M A S
Merz Aest hetic s Scale 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 2 1 of 8 7
A b brevi ati o n / Ter m
Defi niti o n
M D
Me dical D oct or
Me d D R A
Me dical Dicti o nar y  for Re g ulat or y  Acti vities
m I TT
M o difie d I nte nti o n-t o-treat
M g
Milli gra m
m L
Milliliter
M T D
Ma xi m u m t olerate d d ose
N or n
N u m ber
N/ A
N ot A p plica ble
O T C
O ver -t he-C o u nter
P E
P h y sical E xa mi nati o n
PI
Pri nci pal I n vesti gat or; q ualifie d pers o n res p o nsi ble f or c o n d ucti n g t he 
st u d y at a st u dy site
Plt
Platelet c o u nt
P P
Per- Pr ot oc ol
P Q C
Pr o d uct Q ualit y  C o m plai nt
P T
Preferre d Ter m
Q A
Q ualit y  Ass ura nce
R A
Re g ulat or y  A ut h orit y
R B C
Re d bl o o d cell
Refere nce pr o d uct
A n i n vesti gati o nal or mar kete d 
pr o d uct (i.e. acti ve c o ntr ol), or 
place b o, use d as a c o m parat or i n a cli nical st u d y
S A E
Seri o us A d verse E ve nt
S A P
Statistical A nal y sis Pla n
S O C
S y ste m Or ga n Class
S O P
Sta n dar d O perati n g Pr oce d ure
S p o ns or File
Esse ntial d oc u me nts relati n g t o a cli nical st u d y as defi ne d i n 
a p plica ble G C P g ui da nce d oc u me nt a n d mai ntai ne d b y  t he S p o ns or.
S L A
S u bject Li ve Assess me nt
St u d y  Files
T he In vesti gat or file a n d t he S p o ns or file
St u d y  Pr o d ucts
T he i n vesti gati o nal pr o d uct a n d t he refere nce pr o d uct u n der st u d y
St u d y  Site
T he l ocati o n(s) w here 
t he st u d y-relate d acti vities are act uall y 
c o n d ucte d
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 2 2 of 8 7
A b brevi ati o n / Ter m
Defi niti o n
T E A E
Treat me nt E mer ge nt A d verse E ve nt
U P T
Uri ne Pre g na nc y  Test
U S
U nite d States
v/ v
V ol u me/ v ol u me
W B C
W hite bl o o d cell
W FI
Water f or i njecti o n
W H O
W orl d Healt h Or ga nizati o n
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 2 3 of 8 7
1. 
B A C K G R O U N D A N D R A TI O N A L E
1. 1
Me dic al B ac k gr o u n d a n d S h ort R ati o n ale f or t he C li nic al St u d y
B ot uli n u m t o xi n ( B o N T) is a p ote nt ne ur ot o xic pr otei n pr o d uce d b y  t he Gra m-p ositi ve a naer o bic 
bacteri u m, Cl ostri di u m b ot uli n u m . T he m olec ule is pr o d uce d nat urall y b y  t hese bacteria t o get her 
wit h a series of access or y pr otei ns, f or mi n g w hat is ter me d t he “t o xi n c o m ple x”. T he ne ur ot o xi n is 
t he ca use of t he se vere a n d p ote ntiall y fatal disease of b ot ulis m. In a d diti o n, t he pr otei n is use d i n 
ver y  s mall q ua ntities as a treat me nt m o dalit y f or aest hetic a n d me dical i n dicati o ns, ma n y of w hic h 
are c haracterize d b y  i ncrease d m uscle acti vit y. B ot uli n u m t o xi ns occ ur i n se ve n k n o w n ser ot y pes 
( A-G) t hat are pr o d uce d b y  differe nt strai ns of Cl ostri di u m b ot uli n u m. Cli nicall y -i m p orta nt
bi ol o gic acti vit y is li mite d pri maril y t o t he A a n d B ser oty pes, of w hic h t he t yp e A ser oty pe ( B o N T-
A) is use d wi del y t hr o u g h o ut t he w orl d f or t he treat me nt of a ra n ge of cli nical c o n diti o ns.
B o N T -A bl oc ks t he release of acet yl c h oli ne i nt o t he ne ur o m usc ul ar j u ncti o n (s yna pse) cleft, 
t here by pr o hi biti n g t he acti vati o n of acet yl c h oli ne rece pt ors. Paresis b y c he mical de ner vati o n t h us 
occ urs i n t he tar get m uscle, lea di n g t o i n hi biti o n of m usc ular c o ntracti o n. T he acti ve ne ur ot o xi n is 
1 5 0 k Da m olec ular wei g ht a n d Q M 1 1 1 4 -D P o nl y  c o ntai ns t his part of t he t o xi n c o m ple x: t here are 
n o ne of t he ot her access or y pr otei ns w hic h are n or mall y  ass ociate d wit h t he 1 5 0 k Da acti ve m oiet y.
Si nce t he 1 9 7 0s, B o N T -A has bee n i n vesti gate d a n d s u bse q ue ntly a p pr o ve d f or t he treat me nt of 
m ulti ple i n dicati o ns ar o u n d t he w orl d .2, 3 Treat me nt of stra bis m us b y  rela xati o n of o veracti ve 
e xtra oc ular m uscles was t he first re p orte d me dical use. 4 Cli nical st u dies f or aest hetic i n dicati o ns 
were first perf or me d i n t he late 1 9 8 0s. 5 Si nce t he n, ma n y  ot her cli nical i n dicati o ns ha ve bee n 
i n vesti gate d,6- 8 alt h o u g h t he n u m ber of a p pr o ve d i n dicati o ns is m uc h s maller. B o N T -A pr o d ucts 
ha ve bee n lice nse d i n t he U S f or t he aest hetic i n dicati o ns of gla bellar li nes ( G L), lateral ca nt hal 
li nes ( LC L ) a n d f ore hea d li nes ( F L), t o get her wit h t hera pe utic i n dicati o ns s uc h as stra bis m us, 
ble p har os pas m, he mifacial s pas m, cer vical d y st o nia, f ocal s pasticity, p r o p h ylactic treat me nt of 
c hr o nic mi grai ne, o veracti ve bla d der a n d h y p er hi dr osis. 
I n t he earl y 1 9 9 0s, patie nts treate d wit h B o N T -A f or ble p har os pas m were o bser ve d t o l ose t heir 
fr o w n li nes a n d, 5 , 9  si nce p u blis hi n g t hese o bser vati o ns, t he use of B o N T-A i n t he aest hetic setti n g 
has ac celerate d. I njecta ble B o N T -A pr o d ucts ha ve bee n i n vesti gate d f or m ulti ple aest hetic 
i n dicati o ns i n atte m pts t o re verse t he a p peara nce of a gi n g, es peciall y in t he facial re gi o n.2 I n t he 
treat me nt of facial li nes, t he effect of B o N T -A i njecti o ns us uall y  persists f or a p pr o xi matel y 4- 6 
m o nt hs. Facial m uscle acti vit y an d se verity of t he facial wri n kles t he n ret ur ns t o baseli ne. F ull 
f u ncti o nalit y of facial m uscles is us uall y rest ore d b y a p pr o xi matel y 6 m o nt hs p ost-treat me nt.1 0
T here is o ne B o N T -A pr o d uct c urre nt l y lice nse d i n t he U S f or t he treat me nt of L C L i n a d ults
( B ot o x C os metic ® ). Q M 1 1 1 4 -D P is a n o vel b ot uli n u m t o xi n t yp e -A 1 w hic h is prese nte d as a li q ui d 
f or m ulati o n. U nli ke t he mai n c o m merciall y a vaila ble b ot uli n u m t o xi ns i n t he U nite d States, 
Q M 1 1 1 4 -D P is ma n ufact ure d a n d f or m ulate d wit h o ut a n y ani mal or h u ma n pr otei ns.  As a n o vel 
B o N T -A wit h a differe ntiate d f or m ulati o n, Q M 1 1 1 4 -D P is bei n g de vel o pe d f or t he treat me nt of 
m o derate t o se vere L C L i n a d ults o ver 1 8 years.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 2 4 of 8 7
1. 2 
St u d y Pr o d uct Pr ofile
1. 2. 1
Dr u g P r ofile
Q M 1 1 1 4 is a pr otei n di mer of 1 5 0 kil o dalt o n ( k Da) 
 
 
 
  U nli ke ot her c o m mercially 
a vaila ble B o N Ts, Q M 1 1 1 4 -D S is ma n ufact ure d a n d f or m ulate d wit h o ut a n y ani mal or h u ma n 
pr otei ns, t here b y re d uci n g t he p ote ntial ris k of viral c o nta mi nati o n i n t he pr o d uct.
1. 2. 2
Pre - Cli nic al D oc ume nt ati o n
T he pre -cli nical p har mac ol o g y -t o xic ol o g y pr o gra m has i ncl u de d a p pr o priate t o xic ol o g y st u dies t o 
s u p p ort safety f or a d mi nistrati o n of Q M 1 1 1 4 -D P at t he pr o p ose d d ose of 6 0 u nits ( U) w hic h will 
be e val uate d i n t his st u d y.
N o safet y phar mac ol o g y or p har mac o ki netic st u dies were c o n d ucte d f or Q M 1 1 1 4 -D P si nce n o 
s yste mic e x p os ure t o t he pr o d uct is e x pecte d wit h a si n gle I M ad mi nistrati o n t o s pecific facial 
m uscles usi n g t he d ose pr o p ose d.  A d diti o nall y , B o N T- A bi n ds wit h hi g h affi nit y  at t he ne ur o nal 
s yna pses at t he l ocal i njecti o n site.1 1 T heref ore, a n y meta b olis m a n d eli mi nati o n of t he pr o d uct 
w o ul d occ ur at t he l ocal site of i njecti o n.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 2 5 of 8 7
1. 2. 3
Cli nic al D oc u me nt ati o n
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI

C O N FI D E N TI A L
Pa ge 2 6 of 8 7
1. 2. 4
D ose R ati o n ale
N o n -cli nical st u dies ha ve s h o w n a si milarit y bet wee n Q M 1 1 1 4 -D P p ote nc y  units a n d S pe y w o o d 
u nits (D y s p ort ® / Azzal ure® ). B ot h safety a n d efficac y for t he 3 0- 9 0 U d ose ra n ge of Q M 1 1 1 4 -D P 
were esta blis he d i n t he p hase 2 st u d y (st u d y CT N 4 3 Q M 1 3 1 3). Base d o n t he e val uati o n of res ults 
f or t he differe nt d ose le vels st u die d t o date i n t he cli nical pr o gra m of Q M 1 1 1 4-D P, t he S p o ns or has 
c o ncl u de d t hat a 6 0 u nit d ose offers a n a p pr o priate bala nce bet wee n efficac y, d urati o n of effect a n d 
safety f or t he treat me nt of LC L .
1. 3
Ris k/ Be nefit A ssess me nt
Base d o n t he cli nical e x perie nce wit h Q M 1 1 1 4 -D P i n t he P hase 1 st u d y 
, s u bjects 
partici pati n g i n t he st u d y ma y  e x perie nce A Es s uc h as a d mi nistrati ve site c o n diti o ns (e. g., i njecti o n 
site er yt he ma or se nsati o n of press ure) or h ea dac he ( Secti o n 1. 2. 3 ). 1 2
 
 T he ris k of A Es 
occ urri n g m a y  be re d uce d b y  usi n g p hys icia ns w h o are e x perie nce d i n t he b ot uli n u m t o xi n i njecti o n 
tec h ni q ue. All 
treati n g I n vesti gat ors will 
b e trai ne d i n t he a d mi nistrati o n tec h ni q ue of 
Q M - 1 1 1 4-D P pri or t o t he st u d y  start.  
T he be nefit t o s u bjects recei vi n g Q M 1 1 1 4 -D P i n t his st u d y will be a te m p orar y re d ucti o n i n t he 
a p peara nc e of t heir L C L.   T he s u bjects i n t he place b o gr o u p are n ot e x pecte d t o gai n a n y cli nical 
be nefit fr o m t heir partici pati o n i n t he st u d y; h o we ver, as t his is a n aest hetic i n dicati o n t here are n o 
se q uelae t o lac k of efficac y be yo n d a disa p p oi nt me nt i n t he re ducti o n of se verit y of t heir L C L. I n 
a d diti o n, o nl y o ne s u bject o ut of f o ur will recei ve place b o i n t he st u d y.
N o a d diti o nal ris ks s pecific t o t he Q M 1 1 1 4 -D P 6 0 U d ose are a ntici pate d , a n d s ufficie nt cli nical 
e x perie nce wit h B o N T-A pr o d ucts wit h si milar m o de of acti o n f or facial aest hetic use at d ose le vels 
c orres p o n di n g t o t he d ose le vels i n t his st u d y de m o nstrate t he p ote ntial be nefit of t he pr o p ose d 
treat me nts. A d verse e ve nts will be rec or de d at eac h st u d y visit, a n d s u bjects will als o be q uerie d f or 
a n y p ote ntial si g ns a n d s y m pt o ms of l ocal a n d dista nt s prea d of t he t o xi n effect .
I n c o ncl usi o n, gi ve n t he a ntici pate d l o w le vel of tra nsie nt a n d acce pta ble ris ks, t he ris k/ be nefit 
assess me nt of t he use of Q M 1 1 1 4 -D P f or t he treat me nt of m o derate t o se vere L C L a p pears t o offer 
a s u bsta ntial cli nical be nefit at reas o na ble ris k .
2.
C LI NI C A L S T U D Y O B J E C TI V E S , E N D P OI N T S, A N D C LI NI C A L H Y P O T H E SI S
2. 1
Cli nic al St u d y O bjecti ves
T he o bjecti ve of t he st u d y is t o e val uate t he efficac y an d safet y of a si n gle d ose of 
6 0 U of Q M 1 1 1 4- D P c o m pare d t o place b o f or t he treat me nt of m o derate t o se vere L C L .
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 2 7 of 8 7
2. 1. 1
Pri m ar y Effic ac y O bjecti ves a n d E n d p oi nts
T he pri mar y  efficac y objecti ve is t o e val uate a si n gle d ose of 6 0 U of Q M 1 1 1 4 -D P c o m pare d t o 
place b o f or t he treat me nt of m o derate t o se vere L C L .
F or t he pri mar y  e n d p oi nt, t he c o m p osite res p o n der rate will be e val uate d at M o nt h 1 usi n g t he L C L-
I L A a n d t he L C L- S L A at ma xi m u m s mile. A c o m p osite res p o n der is defi ne d as a s u bject w h o 
ac hie ves gra de/le vel 0 or 1 i n L C L se verity a n d at least 2 gra des i mpr o ve me nt fr o m baseli ne o n b ot h 
t he LC L -I L A a n d L C L-S L A scales c o nc urre ntl y.
2. 1. 2
Sec o n d ar y Effic ac y O bjecti ves a n d E n d p oi nts
T he sec o n dar y  efficac y o bjecti ve a n d e n d p oi nts of t he st u d y  are:
O bjecti ve: T o e val uate t he efficac y of a si n gle d ose of 6 0 U of Q M 1 1 1 4 -D P c o m pare d t o place b o 
f or t he treat me nt of m o derate t o se vere L C L.
E n d p oi nt s:
Perce nta ge of s u bjects w h o ac hie ve gra de 0 or 1 at 

M o nt h 1 usi n g L C L -I L A at ma xi m u m s mile.

Eac h p ost -treat me nt visit (e xcl u di n g M o nt h 1) usi n g L C L- I L A at ma xi m u m s mile.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 2 8 of 8 7
2. 1. 4
S afet y O bjecti ves a n d E n d p oi nts
T he safet y o bjecti ve is to e val uate t he safet y of a si n gle d ose of 6 0 U of Q M 1 1 1 4 -D P c o m pare d t o 
place b o f or t he treat me nt of m o derate t o se vere L C L .
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 2 9 of 8 7
Safet y  e n d p oi nts i ncl u de:

I nci de nce a n d se verit y of treat me nt e mer ge nt a d verse e ve nts (T E A Es )

F oc use d p h ys ical e xa mi nati o n ( FP E ) fi n di n gs

Vital si g ns

Electr ocar di o gra m ( E C G)

La b orat or y  para meters (cli nical c he mistr y a n d he mat ol o g y)

Ne utralizi n g a nti b o d y pr o d ucti o n 
2. 2
Cli nic al H y p ot hesis
T he cli nical h y p ot hesi s of t he st u d y is t hat Q M 1 1 1 4 -D P is m ore effecti ve t ha n place b o f or t he 
treat me nt of m o derate t o se vere L C L a n d has a n acce pta ble safet y  pr ofile.
3.
O V E R A L L C LI NI C A L S T U D Y D E S C RI P TI O N
T his is a p hase 3 , m ulti -ce nter, ra n d o mize d, d o u ble bli n d, place b o -c o ntr olle d st u d y to assess t he 
efficac y a n d safety of 6 0 U of Q M 1 1 1 4 -D P f or t he treat me nt of m o derate t o se vere L C L. 
F oll o wi n g t he i nf or me d c o nse nt a n d t he scree ni n g pr ocess, eli gi ble s u bjects will be ra n d o mly 
assi g ne d i n a 3: 1 rati o t o recei ve a si n gle treat me nt at baseli ne of 6 0 u nits Q M 1 1 1 4 -D P ( 2 2 5 s u bjects) 
or place b o ( 7 5 s u bjects) i n t he L C L areas. Ra n d o mizati o n will be stratifie d b y st u d y ce nter. 
Eac h s u bject will recei ve a si n gle treat me nt di vi de d e q uall y am o n g 6 i njecti o n p oi nts ( 0. 1 m L  per 
i njecti o n p oi nt) i n t he L C L re gi o n.   
F oll o wi n g treat me nt at b aseli ne, s u bjects will be m o nit ore d f or safet y a n d efficac y acc or di n g t o t he 
Sc he d ule of Assess me nts (Ta ble 2 ).
Ef ficac y assessme nts will i ncl u de ( Secti o n 7. 1 ):

I n vesti gat or 4- p oi nt P h ot o gra p hic Scale of L C L  Se verit y at 
 
ma xi m u m s mile (I n vesti gat or assess me nt [ L C L -I L A])

S u bject 4- p oi nt P h ot o gra p hic Scale of L C L Se verit y  at 
 ma xi m u m 
s mile (s u bject assess me nt [ LC L -S L A])
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 3 0 of 8 7
Safet y  assess me nts will i ncl u de ( Secti o n 7. 2 ):

A d verse e ve nts ( A Es)

F P E

Vital si g ns

E C G

La b orat or y  safety tests (c he mistr y  a n d he mat ol o g y)

Pr o d ucti o n of n e utralizi n g a nti b o dies a gai nst Q M 1 1 1 4 -D P
Selecti o n criteria f or t he st u d y po p ulati o n are descri be d i n Secti o n 5 . Detaile d i nf or mati o n a b o ut 
st u d y tas ks b y treat me nt visit is o utli ne d i n Secti o n 8 a n d i n Ta ble 2 . I nf or mati o n re gar di n g cli nical 
s u p plies a n d treat me nt pr oce d ure are pr o vi de d i n Secti o n 0 .
4.
C LI NI C A L S T U D Y D U R A TI O N A N D T E R MI N A TI O N
T he pla n ne d d urati o n of recr uit me nt (fr o m first s u bject first visit [ F S F V] t o last s u bject first visit 
[ LS F V]) is a p pr o xi matel y  3 m o nt hs.
T he pla n ne d cli nical st u d y durati o n fr o m F S F V t o last s u bject last visit (L S L V) is a p pr o xi matel y 
9. 5 m o nt hs.
Cli nical st u d y partici pati o n f or eac h s u bject is a p pr o xi matel y 6. 5 m o nt hs.
T he S p o ns or ma y  deci de t o pre mat urel y ter mi nate or s us pe n d t he partici pati o n of a partic ular cli nical 
st u d y ce nter (for e xa m ple, lac k of s u bject e nr oll me nt or n o n- c o m plia nce wit h cli nical st u d y pr ot oc ol, 
re g ulati o n, or G C P) or pre mat urel y s us pe n d t he cli nical st u d y (for e xa m ple, f or safety, st u d y pr o d uct
q ualit y , re g ulat or y, efficac y, or l o gistical reas o ns) at a n y ti me wit h a p pr o priate n otificati o n.
5. 
S E L E C TI O N A N D DI S P O SI TI O N O F C LI NI C A L S T U D Y P O P U L A TI O N
5. 1
N u m ber of S u bjects
As a scree n fail ure rate of a p pr o xi matel y  10 pe rce nt is a ntici pate d, a p pr o xi matel y 33 0 s u bjects will 
be scree ne d i n or der t o get 3 0 0 s u bjects e nr olle d i n a 3: 1 rati o t o Q M 1 1 1 4 -D P 6 0 U ( N = 2 2 5) or 
place b o ( N = 7 5). It is e x pecte d t hat eac h ce nter will recr uit a si milar n u m ber of s u bjects.
5. 2
Cli nic al St u d y P o p ul ati o n C h ar acteristics
I n or der t o be eli gi ble f or t he cli nical st u d y, s u bjects m ust f ulfill all of t he f oll o wi n g criteria. T hese 
criteria are a p plica ble at b ot h scree ni n g a n d baseli ne u nless ot her wise s pecifie d. 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 3 1 of 8 7
5. 2. 1
I ncl usi o n C riteri a
1.
Male or fe male 1 8 ye ars of a ge or ol der .
2.
M o derate t o se vere bilaterall y  sy m metrical L C L ( gra de 2 or 3 o n t he 4- p oi nt P h ot o gra p hic Scale 
ra n gi n g fr o m 0 [ n o ne] t o 3 [se vere]) at ma xi m u m s mile as assesse d b y  the I n vesti gat or li ve 
assess me nt ( L C L -I L A).
3.
B ilaterall y sy m metrical L C L gra de d as Le vel 2 or Le vel 3 o n t he 4- p oi nt P h ot o gra p hic Scale 
(ra n gi n g fr o m Le vel 0 t o Le vel 3) at ma xi m u m s mile as assesse d b y  t he s u bject li ve assess me nt 
( LC L -S L A).
4.
Fe male of n o n -c hil d beari n g p ote ntial (i.e., p ost -me n o pa usal [a bse nce of me nstr ual blee d i n g f or 
1 y ear pri or t o scree ni n g, wit h o ut a n y  ot her me dical reas o n], or has u n der g o ne h ysterect o m y or 
bilateral o o p h orect o m y ).
O R
Fe male of c hil d beari n g p ote ntial wit h a ne gati ve uri ne pre g na nc y test at scree ni n g a n d baseli ne, 
a n d a grees t o use a hi g hl y  effecti ve a n d a p pr o ve d c o ntrace pti ve met h o d f or t he d urati o n of t he 
st u d y. A hi g hly effecti ve met h o d of c o ntrace pti o n is defi ne d as:

Bilateral t u bal li gati o n;

C o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) oral, i ntra va gi nal or tra ns der mal 
c o ntrace pti ves t hat i n hi bit o v ulati o n as t he pri mar y m o de of acti o n, o n a sta ble d ose f or at 
least 2 8 da ys pri or t o scree ni n g visit;

I ntra uteri ne de vice (I U D) i nserte d at least 2 8 da ys pri or t o scree ni n g visit; 

I ntra uteri ne h or m o ne-releasi n g sys te m;

Part ner vasect o mize d f or at least t hree m o nt hs pri or t o scree ni n g visit;

Pr o gest o ge n - o nly oral, i njecta ble or i m pla nta ble c o ntrace pti ves t hat i n hi bit o v ulati o n as 
t he pri mar y  mo de of acti o n, o n a sta ble d ose f or at least 2 8 da y s pri or t o scree ni n g visit; 
or

Strict a bsti ne nce (i.e., refrai ni n g fr o m heter ose x ual i nterc o urse f or t he e ntire d urati o n of 
t he s u bject’s partici pati o n i n t he st u d y).
5.
Ti me a n d a bilit y  t o c o m plete t he st u d y a n d c o m pl y wit h i nstr ucti o ns.
6.
U n dersta n ds t he st u d y re q uire me nts a n d si g ne d t he i nf or me d c o nse nt f o r m (IC F).
5. 2. 2
E x cl usi o n Criteri a
1.
Pre vi o us use of a n y B ot uli n u m t o xi n treat me nt i n facial areas wit hi n 9 m o nt hs pri or t o st u d y 
treat me nt.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 3 2 of 8 7
2.
A ntici pate d nee d f or treat me nt wit h b ot uli n u m t o xi n of a n y ser ot ype f or a n y reas o n d uri n g t he 
st u d y ( ot her t ha n t he i n vesti gati o nal pr o d uct).
3.
Fe male w h o is pre g na nt, breast fee di n g , or i nte n ds t o c o ncei ve a c hil d d uri n g t he st u d y .
4.
K n o w n aller g y or h y per se nsiti vit y to a n y c o m p o ne nt of t he i n vesti gati o nal pr o d uct ( Q M 1 1 1 4 -
D P) or a n y b ot uli n u m t o xi n ser ot y p e .
5.
I na bilit y to s u bsta ntiall y re d uce t he a p peara nce of facial r hyt i des i n t he treat me nt area b y  
p h y sically s prea di n g t he m a part, as deter mi ne d b y t he i n vesti gat or.
6.
Cli nicall y  si gnifica nt a b n or mal f oc use d p h ysical e xa mi nati o n fi n di n g(s) at scree ni n g or baseli ne 
visits , i n the i n vesti gat or’s o pi ni o n .
7.
E xcessi ve s ki n la xit y  i n t he treat me nt area or peri or bital area.
8.
Pre vi o us use of a n y h yal ur o nic aci d s oft tiss ue a u g me ntati o n t hera py i n t he lateral ca nt hal area
wit hi n 6 m o nt hs bef ore baseli ne .
9.
Pre vi o us s oft tiss ue a u g me ntati o n wit h a n y per ma ne nt ( n o n-bi o de gra da ble s uc h as silic o ne, 
p ol y acr yla mi de, etc) or se mi-per ma ne nt (i.e. calci u m h y dr o x yl a patite, p ol y - L-Lactic aci d or 
p ol y met h y l-met hacr y late) pr o d uct; lifti n g t hrea ds, or a ut ol o g o us fat i n t he treat me nt area .
1 0. Hist or y , prese nce or pre dis p ositi o n of e yeli d or e ye br o w pt osis ( hea vy e ye br o ws), a m bl y o pia 
(i.e., laz y eye ), or pre vi o us s ur ger y ar o u n d t he e ye t hat m a y  lea d t o t he a b o ve e ve nts, as 
deter mi ne d b y t he I n vesti gat or.
1 1. Mar ke d facial as y m metr y , e xcessive der mat oc halasis (i.e., e xcess of s ki n i n e yeli ds), or mar ke d 
peri oc ular or e y e br o w as ym metr y .
1 2. Prese nce of scar(s), pierci n g(s), or tatt o o (s) (i ncl u di n g micr o bla di n g of e y e br o w or e yeli ner) i n 
t he treat me nt area or ar o u n d t he treat me nt area t hat, i n t he I nvesti gat or's o pi ni o n , ma y  i nterfere 
wit h st u d y  e val uati o ns. 
1 3. Prese nce of i nfla m mati o n, acti ve i nfecti o n or s ki n dis or der, s uc h as ecze ma, r osacea, facial 
ps oriasis, her pes z oster etc., near or i n t he treat me nt area.
1 4. P rese nce of ca ncer o us or pre-ca ncer o us lesi o ns i n t he treat me nt area. 
1 5. Hist or y  of ot her facial treat me nt, s ur ger y, aest hetic pr oce d ures (e. g. a blati ve s ki n res urfaci n g, 
laser treat me nt micr o nee dli n g, or c he mical peel ) i n t he pre vi o us 1 2 m o nt hs t hat, i n t he 
i n vesti gat or’s o pi ni o n, c o ul d i nterfere wit h st u d y i njecti o ns a n d/ or assess me nts or e x p ose t he 
s u bject t o u n d ue ris k b y st u d y partici pati o n.
1 6. Pla n ne d facial s ur ger y, e ye s ur ger y (i ncl u di n g L A SI K pr oce d ure) or aest hetic pr oce d ures (e. g. 
a blati ve s ki n res urfaci n g, laser treat me nt, micr o nee dli n g,
or c he mical peel i n t he u p per or 
mi dfacial area) d uri n g t he st u d y  peri o d.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 3 3 of 8 7
1 7. Hist or y  or prese nce of facial ner ve pals y, or a n y me dical c o n diti o n t hat ma y p ut t he s u bject at 
i ncrease d ris k wit h e x p os ure t o b ot uli n u m t o xi n i ncl u di n g dia g n ose d m y ast he nia gra vis , 
La m bert -Eat o n s yn dr o me, a m yotr o p hic lateral scler osis, or a n y ot her c o n diti o n t hat mi g ht 
i nterfere wit h ne ur o m usc ular f u ncti o n. 
1 8. Use of me dicati o ns t hat affect ne ur o m usc ular tra ns missi o n s uc h as c urare-li ke de p olarizi n g 
a ge nts, li nc osa mi des, p ol y m y x i ns, a ntic h oli nesterases, a n d a mi n o gl yc osi de a nti bi otics.
1 9. S u bject wit h blee di n g dis or der or s u bject c urre ntl y usi n g a ntic oa g ula nts.
2 0. S u bject has a n y  pri or or c urre nt ps yc hiatric ill ness (e. g. ps yc h osis, de pressi o n, a n xiet y), alc o h ol 
or dr u g a b use, or is ta ki n g a nti de pressa nt, a n xi ol ytic, or a nti ps yc h otic me dicati o n t hat, i n t he 
I n vesti gat or's o pi ni o n, c o ul d affect t he s u bject's safety a n d/ or t he c o n d uct or o utc o me of t he 
st u d y.
2 1. Ot her c o nc urre nt me dical c o n diti o ns, t hera py, or ot her c o n diti o n t hat i n t he I n vesti gat or's 
o pi ni o n w o ul d i nterfere wit h t he e val uati o n of t he st u d y me dicati o n safet y or efficac y a n d/ or p ut 
t he s u bject at ris k if he/s he partici pates t o t he st u d y.
2 2. Partici pati o n i n a n i n vesti gati o nal de vice or dr u g st u d y wit hi n 3 0 d a y s pri or t o st u d y treat ment 
or pla ns t o e nr oll i n a n y ot her i n vesti gati o nal st u d y d uri n g partici pati o n i n t his st u d y .
2 3. St u d y  ce nter pers o n nel, cl ose relati ves of t he st u d y ce nter pers o n nel (e. g. pare nts, c hil dre n, 
si bli n gs, or s p o use), e m pl o yees or cl ose relati ves of e m pl o y ees at the S p o ns or c o m pa n y .
5. 3
Me dic al Hist or y
Rele va nt hist or y  of s ur gical e ve nts a n d me dical c o n diti o ns s hall be d oc u me nte d i n t he s u bject’s 
st u d y file a n d electr o nic case re p ort f or m (e C R F) usi n g me dical ter mi n ol o g y .
5. 4
Pre vi o us a n d C o nc o mit a nt T her a pies
5. 4. 1
Defi niti o n
Pre vi o us t hera pies are defi ne d as t hera pies t hat ha ve bee n st o p pe d wit hi n t he 4 wee ks prece di n g t he 
scree ni n g visit or wit hi n ti mefra mes s pecifie d i n t he i ncl usi o n/excl usi o n criteria .
C o nc o mita nt t hera pies are defi ne d as f oll o ws:

a n y e xisti n g t hera pies o n g oi n g at t he ti me of t he scree ni n g visit,

a n y cha n ges t o e xisti n g t hera pies (s uc h as c ha n ges i n d ose or f or m ulati o n) d uri n g t he c o urse 
of t he cli nical st u d y, or

a n y ne w t hera pies recei ve d b y t he s u bject si nce t he scree ni n g visit.  
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 3 4 of 8 7
5. 4. 2
C ate g ories
T he f oll o wi n g t w o cate g ories are t o be c o nsi dere d f or pre vi o us a n d c o nc o mita nt t hera pies: 

Dr u gs
i ncl u di n g b ut n ot li mite d t o, prescri pti o n, o ver -t he-c o u nter ( O T C), birt h c o ntr ol 
pills/ patc hes/ h or m o nal de vices, vita mi ns, her bal me dici nes/s u p ple me nts, a n d h o me o pat hic 
pre parati o ns.

Me dical a n d s ur gical pr oce d ures i ncl u di n g, b ut n ot li mite d t o, laser/ra diati o n pr oce d ures, 
der mal fillers (area of treat me nt s h o ul d be i n dicate d), X-ra ys, s ur geries, t o ot h e xtracti o ns.
5. 4. 3
Rec or di n g
Pre vi o us a n d c o nc o mita nt t hera pies are t o be rec or de d i n t he s u bject’s s o urce d oc u me nts a n d e C R Fs.
C o nc o mita nt t hera pies are t o be re vie we d at eac h visit a n d u p date d i n t he s o urce d oc u me nts a n d 
e C R Fs as nee de d . 
A n y  ne w c o nc o mita nt t hera py or m o dificati o n of a n e xisti n g t hera py ma y be li n ke d t o a n A E. 
A 
c orres p o n di n g A E for m s h o ul d be c o m plete d t o acc o u nt f or t he c ha n ge i n t hera py, e xce pt i n s o me 
cases s uc h as t hera p y use d f or pr o p h yl a xis, d ose m o dificati o n f or a c hr o nic c o n diti o n, etc.
5. 4. 4
A ut h orize d C o nc o mit a nt T her a pies
U nless liste d i n pr o hi bite d c o nc o mita nt t hera pies (see Secti o n 5. 4. 5 ), all are a ut h orize d.
5. 4. 5
Pr o hi bite d C o nc o mit a nt T her a pies
T he f oll o wi n g t hera pies are pr o hi bite d beca use t he y ma y interfere wit h t he efficac y an d/ or safet y 
assess me nt of t he st u d y pr o d ucts(s):
       B ot uli n u m t o xi n of a n y ser ot y pe.
       A n y  ot her i n vesti gati o nal ne w dr u g or de vice.
       A n y  a bs or ba ble (te m p orar y) or n o n-a bs or ba ble ( per ma ne nt) material i n t he treat me nt area.
       Facial aest hetic pr oce d ures (e. g., a blati ve s ki n res urfaci n g, laser treat me nt, micr o nee dli n g, 
p h ot o d y na mic t hera py,  tatt oi n g or c he mical peel) or a n y ot her pr oce d ures i n t he treat me nt
area.
       F acial s ur ger y or e ye s ur ger y (i ncl u di n g L A SI K pr oce d ure).
       Me dicati o ns t hat affect ne ur o m usc ular tra ns missi o n s uc h as c urare-li ke de p olarizi n g a ge nts, 
li nc osa mi des, p ol ym y xi ns, a ntic h oli nesterases a n d a mi n o gl yc osi de a nti bi otics.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 3 5 of 8 7
If a pr o hi bite d t hera p y bec o mes a necessar y treat me nt f or best cli nical i nterest of t he s u bject or d ue 
t o safety reas o n, t he Me dical M o nit or ( Secti o n 1 1. 9 ) s h o ul d be n otifie d, if ti me per mits, t o disc uss 
p ossi ble alter nati ves pri or t o a d mi nistrati o n of a pr o hi bite d t hera p y .
If a s u bject recei ves a pr o hi bite d t hera py d uri n g t he cli nical st u dy,  the Me dical 
M o nit or 
( Secti o n 1 1. 9 ) s h o ul d be n otifie d t o disc uss t he s u bject’s c o nti n uati o n i n t he cli nical st u d y.
5. 5
Pr oce d ures/ Re as o ns f or S u bject D isc o nti n u ati o n
A n I n vesti gat or ma y  deci de t o disc o nti n ue a s u bject fr o m t he cli nical st u d y f or safet y reas o ns.
Alt h o u g h t he i m p orta nce of c o m pleti n g t he e ntire cli nical st u d y s h o ul d be e x plai ne d t o t he s u bject 
b y  t he cli nical st u d y pers o n nel, a n y  s u bject is free t o disc o nti n ue partici pati o n i n t his cli nical st u d y
at a n y ti me a n d f or w hate ver reas o n, s pecifie d or u ns pecifie d, a n d wit h o ut a n y prej u dice.  No 
c o nstrai nts are t o be i m p ose d o n t he s u bject, a n d w he n a p pr o priate, a s u bject m a y  be treate d wit h 
ot her c o n ve nti o nal t hera p y  w he n cli nically i n dicate d. 
W he n a s u bject d oes n ot c o m plete t he cli nical st u d y,he/s he will be f ull y assesse d, if s uc h assess me nt 
is p ossi ble.  The pr oce d ures desi g nate d f or t he M o nt h 6/ E T visit s h o ul d be c o m plete d f or all s u bjects 
disc o nti n ui n g t he cli nical st u d y a n d t he a p pr o priate e C R F s h o ul d be c o m plete d.
All disc o nti n uati o ns a n d t he reas o n f or disc o nti n uati o n are t o be d oc u me nte d b y t he I n vesti gat or o n 
t he e xit for m. F or disc o nti n uati o n d ue t o a n A E, t he A E for m is t o be c o m plete d. T he I n vesti gat or 
s h o ul d als o e ns ure t hat t he s u bject recei ves s uita ble t hera py f or t he A E.
P ote nti al reas o ns f or disc o nti n uati o n are liste d bel o w:

A d verse E ve nt:
C o m plete a n A E f or m.

Wit h dra wal b y  
S u bject:
I ncl u des c o nse nt wit h dra wal, s u bject rel ocati o n, sc he d ule c o nflicts, etc.  
E x plai n t he reas o n f or wit h dra wal i n t he c o m me nt secti o n of t he e C R F
exit f or m.

L ost t o 
F oll o w - u p:
C o nfir me d wit h t w o d oc u me nte d p h o ne calls a n d a certifie d letter 
( deli ver y recei pt re q ueste d) wit h o ut a ns wer.  Ex plai n i n t he c o m me nt 
secti o n of t he e C R F e xit f or m.

Ot her:
T his cate g or y is t o be use d f or a s u bject w h o disc o nt i n ues d ue t o a 
reas o n ot her t ha n as s pecifie d i n t he pre defi ne d cate g ories a b o ve.  
E x plai n t he reas o n f or disc o nti n uati o n i n t he c o m me nt secti o n of t he 
e C R F exit f or m.
A s u bject w h o has bee n ra n d o mize d a n d assi g ne d a kit n u m ber/ra n d o mizati o n n u m ber ca n n ot be 
re place d b y  an ot her s u bject if he/s he disc o nti n ues t he cli nical st u d y f or a n y reas o n. A d diti o nal 
s u bjects c o ul d be e nr olle d (ra n d o mize d/assi g ne d t o treat me nt) i n or der t o attai n t he n u m ber of 
e val ua ble s u bjects.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 3 6 of 8 7
Pre g na ncies occ urri n g d uri n g t he scree nin g peri o d are c o nsi dere d scree n fail ures; t he y sh o ul d be 
rec or de d as s uc h i n t he e C R F a n d n o pre g na nc y  for m is t o be c o m plete d. I n case of a pre g na nc y 
occ urri n g after t he baseli ne visit, f oll o w t he pr oce d ures descri be d i n Secti o n 7. 2. 6. 2. 3 . T he s u bject 
ma y  re mai n i n t he st u d y, b ut n o i n vasi ve pr oce d ure s h o ul d be c o n d ucte d (e. g. n o sa m ple ta ke n f or 
la b test).
T he S p o ns or ma y  als o deci de t o pre mat urel y ter mi nate or s us pe n d a s u bject’s partici pati o n i n t he 
cli nical st u d y.
6.
C LI NI C A L S U P P LI E S
Details of t he dr u g c o m p ositi o n a n d e xci pie nts are pr o vi de d i n t he c urre nt Q M 1 1 1 4 -D P I n vesti gat ors 
Br oc h ure. 1 2
6. 1
Cli nic al S u p pl y I de ntific ati o n a n d U se
6. 1. 1
Q M 1 1 1 4 -D P
T he i n vesti gati o nal pr o d uct ( Q M 1 1 1 4-D P) will be s u p plie d as a sterile s ol uti o n for i njecti o n 
c o ntai ni n g t he dr u g s u bsta nce, Q M 1 1 1 4 -D S.  The dr u g s u bsta nce is a B o N T T y pe A. Q M 1 1 1 4 -D S 
is dil ute d i n a b uffer s ol uti o n.  
At t he baseli ne visit, a t otal v ol u me of 0. 6 m L  of Q M 1 1 1 4 -D P will be a d mi nistere d i n 6 e q ual 
ali q u ots of 0. 1 m L eac h p er t he bli n de d ra n d o mizati o n assi g n me nt .
6. 1. 2
Pl ace b o
Place b o will be s u p plie d as a b uffere d s ol uti o n f or i njecti o n c o ntai ni n g o nl y  the b uffer s ol uti o n of 
Q M 1 1 1 4 - D P; place b o d oes n ot c o ntai n acti ve dr u g s u bsta nce. 
At t he baseli ne visit, a t otal v ol u me of 0. 6 m L  of place b o will be a d mi nistere d i n 6 e q ual ali q u ots of 
0. 1 m L  eac h per t he bli n de d ra n d o mizati o n assi g n me nt .
T he place b o pr o d uct s h o ul d be st ore d at t he rec o m me n de d te m perat ure ( bet wee n 2° C a n d 8° C ; 3 6 
º F – t o 4 6 º F). T he place b o pr o d uct s h o ul d n ot be fr oze n a n d s h o ul d be pr otecte d fr o m li g ht.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 3 7 of 8 7
6. 1. 3
St u d y Pr o d uct D escri pti o n
T a ble 3
Descri pti o n a n d Us a ge of t he S t u d y Pr o d ucts
I n vesti g ati o n al pr o d uct
Refere nce pr o d uct
N a me of dr u g s u bst a nce  
Q M 1 1 1 4 -D S
N/ A
I nter n al C o de
Q M 1 1 1 4 -D P
Place b o
P h ar m ace utic al F or m
S ol uti o n f or i njecti o n
S ol uti o n f or i njecti o n
C o nce ntr ati o n
1 0 0 u nits/ m L, b uffere d s ol uti o n
N/ A , b uffer s ol uti o n
D os a ge
6 0 u nits
0. 6 m L t otal
0. 1 m L per i njecti o n p oi nt
N/ A
0. 6 m L t otal
0. 1 m L per i njecti o n p oi nt
R o ute
I ntra m usc ular i njecti o n
I ntra m usc ular i njecti o n
D ose re gi me n 
Si n gle treat me nt at b aseli ne visit
Si n gle treat me nt at b aseli ne visit
L oc ati o n of tre ate d are a
Lateral ca nt h us areas
Lateral ca nt h us areas
6. 1. 4
S u bject I de ntific ati o n N u m ber ( SI N) 
Eac h st u d y partici pa nt w h o has si g ne d t he I C F will be e ntere d i nt o t he e C R F s yste m a n d a s u bject 
n u m ber will be assi g ne d via t he e C R F s yste m. F or t he d urati o n of t he st u d y, t he s u bject will be 
i de ntifie d usi n g t he s u bject n u m ber f or all d oc u me ntati o n a n d disc ussi o n.
S u bject n u m bers will c o nsist of t he st u d y ce nter n u m ber f oll o we d b y  a c o nsec uti ve n u m ber starti n g 
wit h 0 0 1 at eac h ce nter. T he s u bject n u m bers s hall be all ocate d i n asce n di n g se q ue ntial or der wit hi n 
eac h ce nter. If a s u bject is dee me d n ot eli gi ble f or t he st u d y partici pati o n, the reas o n f or scree n 
fail ure s h o ul d be s pecifie d. A scree n fail ure ca n n ot be re -scree ne d.
A l o g/listi n g s h o ul d be mai ntai ne d b y  eac h site f or all s u bjects w h o ha ve si g ne d t he I CF. T here 
s h o ul d be sufficie nt i nf or mati o n t o li n k t he e C R F t o a st u d y su bject’s s o urce d oc u me nts a n d me dical 
rec or ds.
6. 1. 5
Met h o d of T re at me nt A ssi g n me nt
Bef ore starti n g t he st u d y,  a ra n d o mizati o n list stratifie d b y st u d y ce nter will be ge nerate d. W he n t he 
I n vesti gat or has c o nfir me d s u bject eli gi bilit y, t he s u bject will be all ocate d a st u d y pr o d uct wit hi n 
t he Electr o nic Data C a pt ure ( E D C) s ys te m. 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 3 8 of 8 7
6. 1. 6
Kit N u m ber/ R a n d o miz ati o n N u m ber
A kit n u m ber /ra n d o mizati o n n u m ber , a u ni q ue n u m ber o n t he la bel of t he st u d y pr o d ucts, will be 
assi g ne d t o eac h eli gi ble s u bject at baseli ne.
Kit n u m ber/ra n d o mizati o n n u m ber will be all ocate d i n asce n di n g se q ue ntial or der t o eac h eli gi ble 
s u bject.
6. 1. 7
I nstr ucti o ns f or U se a n d A d mi nistr ati o n
Q M 1 1 1 4 -D P ( 6 0 U) will be c o m pare d t o place b o i n t his st u d y an d a d mi nistere d base d o n 
ra n d o mizati o n.
Place b o is i de ntical i n a p peara nce t o t he acti ve Q M 1 1 1 4 - D P b ut c o ntai ns n o acti ve dr u g s u bsta nce.
Q M 1 1 1 4 -D P a n d place b o are a d mi nistere d i n e xactl y the sa me w a y . All treati n g I n vesti gat ors will 
be trai ne d i n t he a d mi nistrati o n tec h ni q ue pri or t o t he st u d y  start.  
Ha n dli n g of acci de ntl y da ma ge d or s pille d st u d y pr o d uct is descri be d i n t he Mater ial Safet y Data 
S heet.
See als o Q M 1 1 1 4 -D P I n vesti gat ors Br oc h ure. 1 2
6. 1. 7. 1
Tre at me nt Pr oce d ure
Pri or t o i njecti o n, t he treat me nt area s h o ul d be clea ne d wit h a s uita ble a ntise ptic s ol uti o n. A n 
a p pr o priatel y size d s yri n ge a n d nee dle (e. g., 3 0- 3 3 ga u ge nee dle ) s h o ul d be use d t o a d mi nister 
treat me nt.
At baseli ne, s u bjects will be ra n d o mize d t o recei ve treat me nt wit h Q M 1 1 1 4 -D P or place b o.  A t otal 
d ose v ol u me of 0. 6 m L  di vi de d i nt o si x e q ual ali q u ots ( 0. 1 m L  per i njecti o n site) will be a d mi nistere d 
i ntra m usc ularly i n t he l ateral ca nt h us areas, 0. 3 m L  per si de. T here are t w o o pti o ns f or t he i njecti o n 
sites i n t he lateral ca nt h us areas; see Fi g ure 2 a n d Fi g ure 3 bel o w. T he i njecti o n site o pti o n f or eac h 
s u bject is base d o n I n vesti gat or discreti o n , a n d s h o ul d be c o nsiste nt f or t he ri g ht a n d left treat me nt 
si des.
I njecti o ns s h o ul d be perf or me d at a 2 0- 3 0° a n gle t o t he s ki n, wit h be vel of nee dle ti p p oi nte d u p 
a n d a wa y fr o m t he e ye a n d ver y  su perficial. All i njecti o n p oi nts, t hree per si de, s h o ul d be at t he 
e xter nal part of t he or bic ularis oc uli m uscle a n d s ufficie ntl y far fr o m t he or bital ri m (at least 1 - 2 
c m). T he i njecti o n p oi nts s h o ul d be se parate d b y 1 -1. 5 c m dista nce. 
W he n li nes i n t he lateral ca nt hal re gi o n a p pears b ot h a b o ve a n d bel o w t he lateral ca nt h us, i nject 
per Fi g ure 2 . I n case li nes i n t he lateral ca nt hal re gi o n are mai nl y  bel o w t he lateral ca nt us, i nject 
per Fi g ure 3 .
T he a nat o mical la n d mar ks ca n be m ore rea dil y ide ntifie d if o bser ve d a n d pal pate d at ma xi m u m 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 3 9 of 8 7
s mile. Care m ust be ta ke n t o a v oi d i njecti n g t he z y g o matic us maj or/ mi n or m uscles t o a v oi d lateral 
m o ut h dr o p a n d as y m metrical s mile.
Fi g ure 2
I njecti o n Sites f or Tre ati n g L C L O pti o n 1
Fi g ure 3
I njecti o n Sites f or Tre ati n g L C L O pti o n 2
6. 1. 7. 2 
P ost- tre at me nt C are
F oll o wi n g treat me nt a d mi nistrati o n at baseli ne, s u bjects will be m o nit ore d at t he st u d y ce nter f or 3 0 
mi n utes. 
S u bjects will be i nstr ucte d t o a v oi d a p pl yi n g press ure, r u b bi n g or massa gi n g t he treate d area, or 
l yi n g face d o w n f or 4 h o urs after treat me nt.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 4 0 of 8 7
6. 1. 7. 3
Tre at me nt Re gi me n
Eac h s u bject will recei ve a si n gle treat me nt wit h Q M 1 1 1 4 -D P or place b o at t he baseli ne visit.
T he treat me nts i n vesti gate d i n t his st u d y  are:

6 0 U of Q M 1 1 1 4 -D P 

Place b o
6. 2
St u d y Pr o d uct P ac k a gi n g a n d L a beli n g
Q M 1 1 1 4 -D P a n d place b o are ma n ufact ure d u n der ase ptic c o n diti o ns. 
 
 
T he la bels will be pri nte d i n E n glis h.  T he te xt of t he la bel will detail t he i nf or mati o n re q ueste d b y  
G o o d Ma n ufact uri n g Practice a n d l ocal re g ulati o ns, a n d at a mi ni m u m i ncl u de t he pr ot oc ol n u m ber, 
st ora ge c o n diti o ns, a n d a n i n vesti gati o nal test article disclai mer (“Ca uti o n: Ne w Dr u g - Li mite d b y  
Fe deral ( or U nite d States) la w t o i n vesti gati o nal use.”)
6. 3
S u p plies M a n a ge me nt
6. 3. 1
Acc o u nt a bilit y
U p o n recei pt of t he st u d y pr o d ucts , t he I n vesti gat or or desi g n ee will mai ntai n acc urate rec or ds of 
t he st u d y pr o d ucts deli ver y  t o t he cli nical st u d y ce nter, t he i n ve nt or y at t he clinical st u d y ce nter, t he 
use b y  eac h s u bject, t he rec o nciliati o n of all st u d y pr o d uct s recei ve d fr o m t he S p o ns or ’s desi g nee , 
a n d t he ret ur n t o t he S p o ns or ’s desi g nee for dis p osal of u n use d st u d y  pr o d ucts .
All st u d y  pr o d ucts se nt t o t he In vesti gat or/I nstit uti o n will be acc o u nte d f or a n d n o u na ut h orize d use 
is per mitte d.
6. 3. 2
St or a ge of S t u d y Pr o d ucts
St u d y  pr o d ucts m ust be st ore d i n a safe a n d sec ure area wit h restricte d access, u n der t he st ora ge 
c o n diti o ns s pecifie d b y t he S p o ns or (see Ta ble 3 ).
6. 3. 3
Dis pe nsi n g a n d R et ur n 
All st u d y pr o d uc ts m ust be i n ve nt orie d a n d a rec or d of t he dis pe nsi n g f or eac h s u bject m ust be 
a p pr o priatel y d oc u me nte d . A n y  dis pe nsi n g err ors m ust be re p orte d t o t he S p o ns or/ C R O a n d 
pr o perl y d oc u me nte d.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 4 1 of 8 7
I n t he e ve nt of earl y ter mi nati o n/s us pe nsi o n of t he cli nical st u d y, a ra pi d recall of st u d y pr o d ucts
will be i nitiate d.  
U n use d or e x pire d st u d y pr o d uct will be ret ur ne d f or destr ucti o n t o t he S p o ns or re prese ntati ve at 
ti me p oi nts a p pr o ve d b y t he S p o ns or.
6. 3. 4
Tre at me nt C o m pli a nce M a n a ge me nt a n d R ec or d
T he treat me nt is a n i njecti o n a d mi nistere d b y  the In vesti gat or. Details of t he i njecti o n pr oce d ure will 
be rec or de d i n t he e C R F a n d s u bject s o urce d oc u me nts . N o ot her meas ure me nts of treat me nt 
c o m plia nce will be ma de.
6. 3. 5
D ose M o dific ati o n 
D ose m o dificati o ns are n ot per mitte d.
6. 3. 6
Pr o d uct Q u alit y C o m pl ai nts
Pr o d uct Q ualit y c o m plai nts ( P Q Cs) s h o ul d be re p orte d t o t he Safet y e-mail liste d i n Secti o n 1 1. 9 . A 
P Q C is a n e x ter nal j u d ge me nt pres u mi n g a q ualit y defect of a pr o d uct; q ualit y  iss ue f or a pr o d uct 
relati n g t o its prese ntati o n or use, i de ntifie d b y  a su bject, a practiti o ner or In vesti gat or site pers o n nel, 
a distri b ut or, or a n y o ne else i n v ol ve d i n cli nical s u p plies ha n dli n g. E xa m ples ma y  incl u de b ut are 
n ot li mite d t o a p peara nce iss ues, o d or, da ma ge d st o p pers, l o w fills, a n d f orei g n matter i n t he pr o d uct. 
T hese c o m plai nts m a y  or m a y  not re prese nt a p ote ntial ris k t o t he s u bject. A P Q C f or m m ust be 
c o m plete d b y t he st u d y ce nter pers o n nel a n d f or war de d t o t he S p o ns or or desi g nee wit hi n 2 4 h o urs 
of a ware ness. Affecte d st u d y pr o d uct s h o ul d be q uara nti ne d, a n d n ot use d, u ntil f urt her n otice b y  
t he S p o ns or.
A d diti o nal c o ntact details are pr o vi de d i n t he I n vesti gat or’s site file.
6. 4
Bli n di n g
T his is a d o u ble -bli n d st u d y i n w hic h neit her t he I n vesti gat or, s u b-I n vesti gat or, st u d y staff, n or t he 
s u bject will k n o w t he s u bject's st u d y pr o d uct assi g n me nt (i.e., Q M 1 1 1 4-D P or place b o). Place b o is 
i de ntical i n a p peara nce t o Q M 1 1 1 4-D P b ut c o ntai ns n o acti ve dr u g s u bsta nce.
S u bjects will be ra n d o mize d at baseli ne t o eit her treat me nt wit h Q M 1 1 1 4 -D P or place b o. I n or der 
t o mai ntai n t he bli n d, t he st u d y pr o d ucts, Q M 1 1 1 4 -D P a n d place b o, will be s u p plie d i n i de ntical 
vials, eac h wit h a u ni q ue n u m ber o n t he vial la bel. B ot h Q M 1 1 1 4 - DP a n d place b o will be 
a d mi nistere d i n e xactl y t he sa me wa y.
A n u n- bli n de d statisticia n will ge nerate t he ra n d o mizati o n sc he d ule; h o we ver, he/s he will n ot b e 
i n v ol ve d i n a n y ot her as pect of t he st u d y pri or t o data base l oc k.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 4 2 of 8 7
T he S p o ns or’s staff or desi g nees directl y i n v ol ve d i n cli nical o perati o ns ma na ge me nt, data 
ma na ge me nt, a n d statistical e val uati o n of t he st u d y will re mai n bli n de d u ntil t he data base is l oc ke d, 
u nless e mer ge nc y  u n bli n di n g is re q uire d. 
6. 4. 1
Verific ati o n of B li n di n g
T he S p o ns or’s staff or desi g n ees will assess a n d verif y  mai nte na nce of t he st u d y bli n d d uri n g t he 
st u d y t hr o u g h r o uti ne m o nit ori n g visits. 
6. 4. 2
U n bli n di n g D uri n g t he C li nic al St u d y
E mer ge nc y  un- bli n di n g d uri n g t he cli nical st u d y ma y  be re q uire d f or t hera pe utic or f or re g ulat or y 
reas o ns (for e x pe dite d safet y  re p orti n g).
A bli n d -brea k s yste m will b e a vaila ble f or I n vesti gat ors.  I n s uc h a n e mer ge nc y, t he I n vesti gat or 
will o nl y  brea k t he bli n d f or t he s u bject i n v ol ve d.
T he I n vesti gat or m ust n otif y  the S p o ns or i m me diatel y in t he e ve nt of s uc h a n e mer ge nc y (see c o ntact 
details i n Secti o n 7. 2. 6. 2. 2 ).  If p ossi ble, t he I n vesti gat or s h o ul d n otif y t he S p o ns or bef ore brea ki n g 
t he bli n d i n or der t o disc uss t his decisi o n wit h t he S p o ns or.  The I nvesti gat or is re q uire d t o d oc u me nt 
eac h case of e mer ge nc y u n bli n di n g, a n d i nf or m t he S p o ns or i m me diatel y.
7.
C LI NI C A L S T U D Y A S S E S S M E N T
7. 1
Effic ac y A ssess me nts
7. 1. 1
I n vesti g at or 4- p oi nt P h ot o gr a p hic Sc ale of L C L Se verit y ( L C L-I L A)
T he vali date d I n vesti gat or 4- p oi nt P h ot o gra p hic Scale of Lateral Ca nt hal Li ne Se verit y ( L C L-I L A)
(A p pe n di x 1 ), de vel o pe d b y  Gal der ma, i ncl u des t w o gra di n g s yste ms: o ne f or t he In vesti gat or li ve 
assess me nts at ma xi m u m s mile, 
. 
T he scale re prese nts L C L se verities fr o m n o ne ( gra de 0), mil d ( gra de 1), m o derate ( gra de 2) , t o 
se vere ( gra de 3). E ac h gra de is als o de picte d b y a n i n di vi d ual p h ot o gra p h a n d descri pti ve te xt. T he 
I n vesti gat ors will be trai ne d o n t he use of t he L C L- I L A.
T he In vesti gat ors will use t he L C L- I L A f or direct, li ve c o m paris o n wit h t he s u bject’s face f or 
gra di n g L C L se verity at scree ni n g, ba seli ne ( pri or t o treat me nt), a n d at all p ost -treat me nt visits. Left 
a n d ri g ht L C L s h o ul d be assesse d se paratel y at 
 ma xi m u m s mile.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI

C O N FI D E N TI A L
Pa ge 4 3 of 8 7
7. 1. 2
S u bject 4- p oi nt P h ot o gr a p hic Sc ale of L C L Se verit y ( L C L -S L A )
T he vali date d S u bject 4- p oi nt P h ot o gra p hic Scale of Lat eral Ca nt hal Li ne Se verit y ( LC L -S L A)
(A p pe n di x 2 ), de vel o pe d b y  Gal der ma, i ncl u des t w o gra di n g s yste ms: o ne f or t he s u bject’s li ve 
assess me nts at ma xi m u m s mile, 
. T he 
scale re prese nts L C L se verities fr o m Le vel 0, Le vel 1, Le vel 2 , t o Le vel 3. E ac h gra de is als o 
de picte d b y a n i n di vi d ual p h ot o gra p h a n d descri pti ve te xt. S u bject s will be trai ne d o n t he use of t he 
L C L- S L A.
S u bjects ma ke t heir assess me nts i n de pe n de ntly of t he I n vesti gat or’s assess me nt. S u bjects will 
e val uate t heir L C L se verit y (left a n d ri g ht si de se parately) at 
 ma xi m u m s mile, 
res pecti vely , at scree ni n g, baseli ne ( pri or t o treat me nt), a n d at all p ost-treat me nt visits.  
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 4 4 of 8 7
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 4 5 of 8 7
7. 2
S afet y A ssess me nts
Safet y assess me nt s will be c o n d ucte d f or all s u bjects at t he ti me p oi nts i n dicate d i n Sc he d ule of 
Assess me nts (Ta ble 2 ).  Safet y  para meters i ncl u de a n e val uati o n of A Es , F P E , vital si g ns, E C G,
la b orat or y safety tests (c he mistr y a n d he mat ol o g y), a n d ne utralizi n g a nti b o d y pr o d ucti o n .
7. 2. 1
F oc use d P h ysic al E x a mi n ati o n ( F P E)
At t he ti me p oi nts i n dicate d i n t he Sc he d ule of Assess me nts (Ta ble 2 ), t he I n vesti gat or or desi g nee 
will perf or m a p h y sical e xa mi nati o n of t he s u bject t hat i ncl u des t he face, hea d, a n d nec k. F urt h er 
details are pr o vi de d i n A p pe n di x 6 .
P ost -baseli ne, t he si g ns a n d s ym pt o ms will als o be m o nit ore d via p h y sical e xa mi nati o n of face, hea d, 
a n d nec k t o e val uate l ocal effect of t o xi n. I n a d diti o n, ge neral p h ysical e xa mi nati o n t o e val uate t he 
re m ote s prea d e ve nts will be c o n d ucte d. T he list of re m ote s prea d of t o xi n e ve nts is c o nsi dere d w hile 
d oi n g cli nical e val uati o ns base d o n s u bject’s s ym pt o ms 
a n d si g ns (A p pe n di x 7).
Directe d
q uesti o ni n g a n d e xa mi nati o n will t he n be perf or me d as a p pr o priate.
T he I nvesti gat or m a y  ch o ose t o i n vesti gate a n y ot her si g n t hat he/s he o bser ves d uri n g t he p h y sical 
e xa mi nati o n. A b n or malities n ote d pre -i njecti o n, i.e. at t he scree ni n g/ baseli ne visits, s h o ul d be 
rec or de d as me dical hist or y a n d ab n or malities n ote d p ost -i njecti o n s h o ul d be rec or de d as A Es.
7. 2. 2
Vit al Si g ns
At t he ti me p oi nts i n dicate d i n t he Sc he d ule of Assess me nts (Ta ble 2 ), eval uat i o n of vital si g ns s hall 
be perf or me d after a p pr o xi matel y 10 mi n utes 
rest i n t he sitti n g p ositi o n. It shall i ncl u de 
meas ure me nt of s yst olic a n d diast olic bl o o d press ure, heart rate, a n d res pirat or y rate. Vital si g ns will 
be ta ke n pri or t o a n y bl o o d dra w, excl u di n g p ost -treat me nt meas ure me nts o n Da y 0.
All a b n or mal val ues at t he baseli ne visit i de ntifie d, as cli nicall y si g nifica nt b y  the In vesti gat or, s hall 
be rec or de d i n t he Me dical Hist or y  f or m.
F or a n y cli nicall y si g nifica nt c ha n ges fr o m t he baseli ne visit, a n A E is t o be rec or de d.
7. 2. 3
Electr oc ar di o gr a m ( E C G)
T he 1 2- lea d E C G rec or di n gs will be ma de after t he s u bjects ha ve bee n resti n g i n a s u pi ne p ositi o n 
f or at least 1 0 mi n utes at t he ti me p oi nts i n dicate d i n Ta ble 2, t he baseli ne E C G s h o ul d be d o ne pri or 
t o treat me nt. T he s u bjects s h o ul d a v oi d p ost ural c ha n ges d uri n g t he E C G rec or di n g s. At eac h ti me-
p oi nt, t he E C G will be rec or de d i n tri plicate. T he tri plicates will be perf or me d at a p pr o xi matel y on e -
mi n ute i nter vals.  
E C Gs will be st ore d electr o nicall y  a n d s u b mitte d t o a ce ntral re vie wer f or a nalys is. Pa per pri nt o uts 
ma y als o be c ollecte d f or ge neral car diac safet y m o nit ori n g at t he cli nical researc h sit e.
Title  
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C O N FI D E N TI A L
Pa ge 4 6 of 8 7
Cli nicall y  si gnifica nt ab n or mal val ues at baseli ne s hall be rec or de d i n t he Me dical Hist or y  for m. F or 
a n y cli nicall y si g nifica nt c ha n ges fr o m baseli ne, a n A E is t o be rec or de d.
T he I n vesti gat or a n d Me dical M o nit or will be alerte d ( e g, e mail) f or E C Gs that are i de ntifie d as 
“a b n or mal, cli nicall y si g nifica nt” b y t he ce ntral E C G la b orat or y.
7. 2. 4
L a b or at or y S afet y Tests
Bl o o d sa m ples will be c ollecte d at baseli ne (pri or t o treat me nt) a n d at M o nt h 6/ E T, a n d se nt t o a 
ce ntral la b orat or y for a nal y sis. I nstr ucti o ns f or bl o o d sa m pli n g are detaile d i n a se parate la b orat or y 
ma n ual.
T he f oll o wi n g la b orat or y safet y tests s hall be perf or me d:

He mat ol o g y : W hite bl o o d cell ( W B C) c o u nt wit h differe ntial, re d bl o o d cell ( R B C) c o u nt, 
hae m o gl o bi n ( H b), he mat ocrit ( hct), a n d plate let c o u nt ( Plt)

Bl o o d c he mistr y: Creati ni ne, urea nitr o ge n, ga m ma gl uta m yl  tra nsferase ( G G T), al kali ne 
p h os p hatase ( A LP), as partate a mi n otra nsferase ( A S T = S G O T), ala ni ne a mi n otra nsferase 
( A L T = S G P T), a n d bilir u bi n (t otal a n d c o nj u gate d)
T he In vesti gat or or a me dicall y q ualifie d s u b-In vesti gat or m ust re vie w a n d e val uate la b orat or y 
val ues f or eac h s u bject i n a ti mel y ma n ner.  Th e In vesti gat or or desi g nee will i nitial a n d date all 
la b orat or y re p orts a n d n ote o n t he re p ort w het her or n ot a n o ut of ra n ge la b orat ory v al ue is cli nicall y 
si g nifica nt. A n o ut of ra n ge la b orat or y  val ue s h o ul d be c o nsi dere d as cli nicall y si gnifica nt if eit her 
of t he f oll o wi n g c o n diti o ns is met:

T he a b n or malit y s u g gests a disease a n d/ or or ga n t o xicit y .

T he a b n or malit y is of a de gree t hat re q uires a d diti o nal acti ve ma na ge me nt, e. g. cl ose 
o bser vati o n, m ore fre q ue nt f oll o w- u p assess me nts, or f urt her dia g n ostic i n vesti gati o n.
F or eac h o ut of ra n ge la b orat or y  res ult, t he In vesti gat or or desi g nee will e nter directl y  i n t he e C R F 
t he In vesti gat or j u d g me nt o n t he prese nce or t he a bse nce of a cli nical si g nifica nce.
All cli nicall y  si g nifica nt o ut of ra n ge la b orat or y val ues f or bl o o d sa m ples c ollecte d at baseli ne will 
be rec or de d i n t he me dical hist or y (re p ort a dia g n osis rat her t ha n a n i n di vi d ual la b or at or y para meter 
a b n or malit y w he ne ver p ossi ble).  
All cli nicall y si gnifica nt o ut of ra n ge la b orat or y val ues f or bl o o d sa m ples c ollecte d after baseli ne 
are t o be re p orte d as a n A E if t his a b n or malit y was n ot prese nt at t he baseli ne visit or is assesse d as 
ha vi n g w orse ne d si nce t he scree ni n g visit (i.e., t here is a si g nifica nt c ha n ge fr o m baseli ne ). 
F or A Es, w he ne ver p ossi ble, t he I n vesti gat or is t o pr o vi de a dia g n osis rat her t ha n t o re p ort i n di vi d ual 
la b orat or y a b n or malities.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
Pa ge 4 7 of 8 7
7. 2. 5
Ne utr a lizi n g A nti b o d y Testi n g
S u bjects will ha ve bl o o d sa m ples ta ke n at baseli ne pri or t o treat me nt , M o nt h 1, a n d M o nt h 6/ E T f or 
meas ure me nt of ser u m ne utralizi n g a nti b o d y testi n g a gai nst Q M 1 1 1 4 -D P . 
A d diti o nal i nf or mati o n a n d detaile d descri pti o n of sa m ple v ol u mes, pr ocessi n g, a n d st ora ge 
re q uire me nt will be i ncl u de d i n a La b orat or y  Ma n ual.
7. 2. 6
A d verse E ve nts
A Es are t o be m o nit ore d t hr o u g h o ut t he c o urse of t he cli nical st u d y fr o m t he ti me t he i nf or me d 
c o nse nt f or m has bee n si g ne d. All A Es are t o be re p orte d o n t he A E f or m of t he e C R F wit h c o m plete 
i nf or mati o n as re q uire d. 
If A Es occ ur, t he mai n c o ncer n s hall be t he safety of t he s u bjects. At t he ti me of t he I C F si g nat ure, 
each s u bject m ust be pr o vi de d wit h t he na me a n d p h o ne n u m ber of cli nical st u d y ce nter pers o n nel 
f or re p orti n g A Es a n d me dical e mer ge ncies.
At eac h p ost e nr oll me nt visit, t he I nvesti gat or ( or s u b-I n vesti gat or) will q uesti o n t he s u bject a b o ut 
A Es usi n g a n o pe n n o n- pers uasi ve q uesti o n t o elicit re p orti n g of A Es, f or e xa m ple “ Ha ve y o u 
n otice d a n y c ha n ge i n y o ur healt h si nce t he last visit?”  Ad diti o nal q uesti o ni n g a n d e xa mi nati o n will 
t he n be perf or me d as a p pr o priate.
7. 2. 6. 1
Defi niti o ns
7. 2. 6. 1. 1
A dverse E ve nts ( A E)
Acc or di n g t o IC H E 2 A, 1 5 a n A E is a n y unt o war d me dical occ urre nce i n a patie nt or a cli nical 
i n vesti gati o n s u bject a d mi nistere d a p har mace utical pr o d uct a n d w hic h d oes n ot necessarily ha ve a 
ca usal relati o ns hi p wit h t his treat me nt. A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n 
(i ncl u di n g a n a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease te m p orall y ass ociate d wit h t he use 
of a me dici nal (i n vesti gati o nal) pr o d uct, w het her or n ot relate d t o t he me dici nal (i n vesti gati o nal) 
pr o d uct.
T h us, a n y ne w si g n, s y m pt o m or disease, or a n y cli nicall y si g nifica nt w orse ni n g of a n e xisti n g si g n, 
s ym pt o m or disease (i ncl u di n g ne w e pis o des of a c hr o nic disease [e. g., h a y  fe ver, aller g y]) c o m pare d 
t o t he c o n diti o n at t he first visit, s h o ul d be c o nsi dere d as a n A E. Lac k of efficac y is n ot c o nsi dere d 
as a n A E.
Title  
D o c i d  
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M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
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N otes:

T here s h o ul d be a n atte m pt t o re p ort a dia g n osis rat her t ha n t he si g ns, s y m pt o ms or a b n or mal 
la b orat or y val ues ass ociate d wit h t he re p ort of a n A E. H o we ver, a dia g n osis s h o ul d be re p orte d 
o nl y  if, i n t he In vesti gat or’s j u d g me nt, it is relati vel y  certai n. Ot her wise, sy m pt o ms, si g ns, or 
la b orat or y val ues s h o ul d be use d t o descri be t he A E.

Pre g na nc y  is n ot t o be c o nsi dere d as a n A E; h o we ver, is a n i m p orta nt me dical e ve nt t hat m ust 
be m o nit ore d as descri be d i n Secti o n 7. 2. 6. 2. 3 .

T he effects of all B o N T pr o d ucts ma y s prea d fr o m t he area of i njecti o n t o pr o d uce s ym pt o ms 
c o nsiste nt wit h B o N T effects. T hese s ym pt o ms ha ve bee n re p orte d h o urs t o wee ks
after 
i njecti o n. Re m ote s prea d of t o xi n t hat affects s wall o wi n g a n d breat hi n g ca n be life t hreate ni n g, 
a n d t here ha ve bee n re p orts of deat h. T he ris k of s ym pt o ms is i ncrease d i n s u bjects w h o ha ve 
u n derl y i n g c o n diti o ns (e. g. dis or ders of t he ne ur o m usc ular j u ncti o n) t hat w o ul d pre dis p ose 
t he m t o t hese sy m pt o ms. B o N T is c o ntrai n dicate d i n i n di vi d uals wit h k n o w n h y perse nsiti vit y 
t o a n y B o N T pre parati o n or t o a n y  of t he c o m p o ne nts i n t he f or m ulati o n. 
7. 2. 6. 1. 2
Tre at me nt E mer ge nt A dverse Eve nt ( T E A E)
A T E A E is a n e ve nt t hat e mer ges d uri n g or after treat me nt, ha vi n g bee n a bse nt pre -treat me nt, or 
w orse ns relati ve t o t he pretreat me nt state.
7. 2. 6. 1. 3
Seri o us A dverse E ve nts ( S A E)
A S A E is a n y u nt o war d me dical occ urre nce t hat at a n y  d ose:

Res ults i n deat h,

Is life-t hreate ni n g,

Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n,

Res ults i n persiste nt or si g nifica nt disa bilit y /inca pacit y , or

Is a c o n ge nital a n o maly/ birt h defect.
I m p orta nt me dical e ve nts t hat ma y n ot res ult i n deat h, be life-t hreate ni n g, or re q uire h os pitalizati o n 
ma y  be c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical j u d g me nt, t he y ma y je o par dize 
t he safety of t he s u bject, a n d m a y  re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he 
o utc o mes liste d i n t his defi niti o n.  E xa m ples of s uc h e ve nts are i nte nsi ve treat me nt i n a n e mer ge nc y 
r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d y scrasia, or c o nv ulsi o ns t hat d o n ot res ult i n 
h os pitalizati o n.
Title  
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M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
Pa ge 4 9 of 8 7
N ote: T he ter m “life-t hreate ni n g” refers t o a n e ve nt i n w hic h t he s u bject was at ris k of deat h at t he 
ti me of t he e ve nt; it d oes n ot refer t o a n e ve nt w hic h h y p ot heticall y mi g ht ha ve ca use d deat h if it 
were m ore se vere.
I n patie nt h os pitalizati o n is c o nsi dere d t o ha ve occ urre d if t he s u bject has ha d t o sta y for a ni g ht at 
t he h os pital.  T he criteri o n f or pr ol o n gati o n of h os pitalizati o n is als o defi ne d as a n e xtra ni g ht at t he 
h os pital.  Hos pitalizati o n ma y  not c o nstit ute s ufficie nt gr o u n ds t o be c o nsi dere d as a n S A E if it is 
s olel y for t he p ur p ose of a dia g n ostic test(s) (e ve n if relate d t o a n A E), electi ve h os pitalizati o n f or 
a n i nter ve nti o n t hat was alrea d y pla n ne d bef ore s u bject e nr ol me nt i n t he cli nical st u dy, a d missi o n 
t o a da y -care facilit y, s ocial a d missi o n (e. g., if t he s u bject has n o place t o slee p), or a d mi nistrati ve 
a d missi o n (e. g., f or a ye arl y e xa mi nati o n).
7. 2. 6. 1. 4
U nex pecte d A dverse D r u g R e acti o n
A n u ne x pecte d a d verse dr u g reacti o n is defi ne d as a n a d verse reacti o n, t he nat ure or se verity of 
w hic h is n ot c o nsiste nt wit h t he a p plica ble st u d y pr o d uct i nf or mati o n (e. g., I n vesti gat or’s Br oc h ure 
f or a n u na p pr o ve d i n vesti gati o nal pr o d uct or t he me dici nal pac ka ge i nsert/s u m mar y of pr o d uct 
c haracteristics f or a n a p pr o ve d i n vesti gati o nal pr o d uct).
7. 2. 6. 1. 5
A dverse E ve nt R e p orti n g P eri o d
T he cli nical st u d y peri o d d uri n g w hic h A Es m ust be re p orte d is t he peri o d fr o m w he n t he s u bject 
si g ne d t he I CF t o t he e n d of t he s u bject’s partici pati o n.
T he S p o ns or s h o ul d be i nf or me d if t he I n vesti gat or bec o mes a ware of a n y u n us ual safet y 
i nf or mati o n or a n y safet y inf or mati o n t hat a p pears t o be dr u g -relate d i n v ol vi n g a s u bject w h o has 
partici pate d i n a cli nical st u d y, e ve n after a s u bject has c o m plete d t he cli nical st u d y.  
7. 2. 6. 1. 6
Severity
Se verit y  is a cli nical deter mi nati o n of t he i nte nsit y of a n A E a n d n ot t he se verit y of a disease.
T he I n vesti gat or is t o classif y the i nte nsit y of A Es usi n g t he f oll o wi n g defi niti o ns as a g ui deli ne.  
F or t his classificati o n, t he I n vesti gat or will ta ke i nt o acc o u nt t he p ossi ble ra n ge of t he i nte nsity of 
t he e ve nt a n d re p ort t he gra de of i nte nsit y whic h is t he m ost a p pr o priate acc or di n g t o his / her me dical 
j u d g me nt.
Mil d
A ware ness of si g ns or s y m pt o m, b ut easil y t olerate d.
M o der ate
Disc o mf ort, e n o u g h t o ca use i nterfere nce wit h us ual acti vit y.
Se vere
I nca pacitati n g wit h i na bilit y t o w or k or perf or m us ual acti vit y.
Title  
D o c i d  
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M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
Pa ge 5 0 of 8 7
7. 2. 6. 1. 7
Rel ati o ns hi p t o t he S t u dy Pr o d uct a n d/ or C li nic al St u dy P r oce d ure
T he I nvesti gat or is t o det er mi ne w het her t here is a reas o na ble ca usal relati o ns hi p bet wee n t he 
occ urre nce of t he A E a n d e x p os ure t o t he st u d y  pr o d uct a n d/ or cli nical st u d y pr oce d ure .
Me dical j u d g me nt s h o ul d be use d t o deter mi ne t he relati o ns hi p, c o nsi deri n g all rele va nt fact ors 
i ncl u di n g t he patter n of reacti o n, te m p oral relati o ns hi ps, rele va nt me dical hist or y , a n d c o nf o u n di n g 
fact ors s uc h as c o-me dicati o n or c o nc urre nt diseases.
T he e x pressi o n “reas o na ble ca usal relati o ns hi p” is mea nt t o c o n ve y  i n ge neral t hat t here are facts or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p (I C H E 2 A, Secti o n III A 1).
T he relati o ns hi p assess me nt f or a n A E is t o be c o m plete d usi n g t he f oll o wi n g defi niti o ns as a 
g ui deli ne:
Re as o n a ble P ossi bilit y: Acc or di n g t o t he re p orti n g I n vesti gat or, t here is a reas o na ble p ossi bilit y  
(i.e., s u g gesti ve e vi de nce or ar g u me nts) t hat t here is a ca usal relati o ns hi p irres pecti ve of t he d ose 
a d mi nistere d bet wee n:

T he st u d y  pr o d uct (acti ve or place b o ) a n d t he A E .

T he cli nical st u d y pr ot oc ol pr oce d ure (e. g., br uisi n g or mar ks fr o m bl o o d dra ws, i njecti o n 
relate d tra u ma, etc.) a n d t he A E .
A t w o -p oi nt scale ( Yes or N o res p o nse) s hall be use d f or t he ca usalit y assess me nt. T he I n vesti gat or 
s hall be as ke d t o i n dicate a res p o nse t o eac h of t he f oll o wi n g q uesti o ns i n t he e C R F:

“ D o y o u c o nsi der t hat t here is a reas o na ble p ossi bilit y that t he e ve nt ma y ha ve bee n ca use d b y 
t he st u d y pr o d uct?”, a n d 

“ D o y o u c o nsi der t hat t here is a reas o na ble p ossi bilit y that t he e ve nt ma y ha ve bee n ca use d b y 
t he st u d y pr o d uct i njecti o n pr oce d ure?”
If a ny of t hese q uesti o ns is a ns were d Yes, t he A E is c o nsi dere d relate d. 
N o Re as o n a ble P ossi bilit y:
N o s u g gesti ve e vi de nce or ar g u me nts ca n be i de ntifie d re gar di n g a 
ca usal relati o ns hi p bet wee n t he st u d y  pr o d uct or t he cli nical st u d y pr o t oc ol pr oce d ure a n d t he A E.
7. 2. 6. 2
Re p orti n g P r oce d ures
7. 2. 6. 2. 1
Pr oce d ures f or R e p orti n g A dverse Eve nts
T he c ollecti o n of A Es is fr o m t he ti me t hat a s u bject si g ns t he I CF t o t heir fi nal visit.
At eac h p ost -e nr oll me nt visit, t he I nvesti gat or ( or s u b-I nvesti gat or) will q u esti o n t he s u bject a b o ut 
A Es usi n g a n o pe n n o n- pers uasi ve q uesti o n t o elicit re p orti n g of A Es, f or e xa m ple “ Ha ve y o u 
n otice d a n y c ha n ge i n y o ur healt h si nce t he last visit?”  Directe d q uesti o ni n g a n d e xa mi nati o n will 
t he n be perf or me d as a p pr o priate. 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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Versi o n: 
Eff e cti v e
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Pri nt date:
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C O N FI D E N TI A L
Pa ge 5 1 of 8 7
A n y  A E occ urri n g d uri n g t he A E re p orti n g peri o d, w het her it is relate d t o t he st u d y  pr o d uct or n ot, 
will be rec or de d i m me diatel y in t he s o urce d oc u me nt, a n d descri be d o n t he A E f or m of t he e C R F
al o n g wit h t he date of o nset, se verit y, relati o ns hi p t o t he st u d y pr o d uct , a n d o utc o me, wit h o ut 
o mitti n g a n y re q ueste d a n d k n o w n i nf or mati o n.  Ad diti o nal i nf or mati o n will be re q ueste d u n der 
certai n circ u msta nces.  
At st u d y en d, A Es assesse d as relate d t o t he treat me nt or st u d y pr oce d ure will be m o nit ore d u ntil 
t he y ha ve res ol ve d or reac he d a sta ble c o n diti o n.  Ot her A Es will be m o nit ore d u ntil t he last visit if 
t he y ha ve n ot res ol ve d or reac he d a sta ble c o n diti o n. 
T he I n vesti gat or will mai ntai n all perti ne nt me dical rec or ds i n t he s u bject’s st u d y  file.  If necessar y 
a n d a p pr o ve d b y  the s u bject or t heir le gal healt h care re prese ntati ve, t he I n vesti gat or m a y  co ntact 
t he s u bject’s pers o nal p h ysicia n or ot her healt h care pr o vi der(s) t o o btai n f urt her details.
F or S A Es (see Secti o n 7. 2. 6. 2. 2 ) a n d pre g na ncies (see Secti o n 7. 2. 6. 2. 3 ), t he S p o ns or is t o be 
i nf or me d i m me diatel y b y e-mail.  The e ve nt m ust be re p orte d t o t he Safet y e-mail wit hi n 2 4 h o urs 
of recei pt of t he i nf or mati o n (c o ntact details i n Secti o n 7. 2. 6. 2. 2 ).
7. 2. 6. 2. 2
Pr oce d ure f or Re p orti n g a Seri o us A dverse Eve nt
F or a S A E occ urri n g d uri n g t he cli nical st u d y, re gar dless of w het her it is relate d t o t he treat me nt or 
n ot, a n d of w het her it is e x pecte d or n ot, t he I n vesti gat or m ust d o t he f oll o wi n g:
1.
Ta ke pr o m pt a n d a p pr o priate me dical acti o n, if necessar y .  The safety o f t he s u bject is t he first 
pri orit y .
2. 
E ns ure t hat t he e ve nt is classifie d as a n S A E ( Secti o n 7. 2. 6. 1. 3 ).
3.
C o m plete t he A E f or m pr o vi de d i n t he e C R F as full y  as p ossi ble.
Pri nt a n d c o m plete t he S A E f or m.  T he c o m plete d f or m, acc o m pa nie d b y  an y ot her rele va nt 
i nf or mati o n or a n o n ymize d me dical rec or ds (e. g., la b orat or y test res ults) wit hi n 2 4 h o urs of 
recei pt of t he i nf or mati o n t o Safet y e-mail liste d bel o w . T he de m o gra p hics, me dical hist or y , 
dr u gs /thera pies f or m, me dical a n d s ur gical pr oce d ures f or m, a n d A E pa ges of t he e C R F m ust 
be c o m plete d a n d a vaila ble f or re vie w i n t he E D C s y ste m at t he ti me of t he re p ort.
4.
I m me diatel y se n d t he c o m plete d S A E re p ort f or m t o t he Safet y  e-mail a n d disc uss f urt her 
acti o ns t o be ta ke n.
E- mail: 
A d diti o nal c o ntact details are pr o vi de d i n t he I n vesti gat or’s site file.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
P P D

C O N FI D E N TI A L
Pa ge 5 2 of 8 7
5.
M o nit or a n d rec or d t he pr o gress of t he e ve nt u ntil it res ol ves or reac hes a cli nicall y sta ble 
o utc o me, wit h or wit h o ut se q uelae.  For all a d diti o nal f oll o w- u p e val uati o ns, se n d all 
a d diti o nal f oll o w- u p i nf or mati o n o n t he S A E t o t he Safet y e-mail wit hi n 2 4 h o urs of recei pt 
of t he u p date d i nf or mati o n.  S A Es will be m o nit ore d u ntil t he I n vesti gat or a n d S p o ns or a gree 
that t he e ve nt is satisfact oril y  res ol ve d.
6.
O btai n a n d mai ntai n i n his/ her files all perti ne nt me dical rec or ds a n d i nf or mati o n re gar di n g 
t he S A E.
7.
I nf or m t he S p o ns or of t he fi nal o utc o me of t he e ve nt.  Se n d a f oll o w u p S A E f or m, w he n
a p pr o priate, t o t he Safety e-mail .
8.
Pr o m pt n otificati o n of S A Es b y  the In vesti gat or t o t he S p o ns or is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safety o f s u bjects are met. T he S p o ns or has 
a le gal res p o nsi bilit y to n otif y  bot h t he l ocal re g ulat or y a ut h orit y an d ot her re g ulat or y age ncies 
a b o ut t he safety of a pr o d uct u n der cli nical i n vesti gati o n. T he S p o ns or will c o m pl y wit h 
c o u ntr y s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g t o re g ulat or y aut h orities, 
I nstit uti o nal Re vie w B oar ds (IR Bs ), a n d In vesti gat ors. I n vesti gat or safet y re p orts are pre pare d 
f or S us pecte d U ne x pecte d Seri o us A d verse Reacti o ns ( S U S A Rs) acc or di n g t o l ocal re g ulat or y 
re q uire me nts a n d t he S p o ns or p olic y  an d are f or war de d t o In vesti gat ors as necessar y . A n 
In vesti gat or w h o recei ves a n In vesti gat or safety re p ort descri bi n g a S A E(s) or ot her s pecific 
safety i nf or mati o n (e. g., s u m mar y or listi n g of S A Es) fr o m t he S p o ns or will file it wit h t he 
I n vesti gat or’s Br oc h ure (I B) a n d will n otif y  the I RB, if a p pr o priate acc or di n g t o l ocal 
re q uire me nts.
9.
C o m pl y  wit h t he a p plica ble re g ulat or y re q uire me nt(s) relate d t o t he re p orti n g of S A Es t o t he 
I RB.
7. 2. 6. 2. 3
Pr oce d ures f or R e p orti n g P re g n a ncies
A n y  pre g na nc y occ urri n g d uri n g t he cli nical st u dy , w here t he fet us c o ul d ha ve bee n e x p ose d t o t he 
st u d y pr o d uct , m ust be m o nit ore d u ntil its o utc o me i n or der t o e ns ure t he c o m plete c ollecti o n of 
safety data.
S u bjects w h o bec o me pre g na nt d uri n g t he scree ni n g peri o d are c o nsi dere d as scree ni n g fail ures; 
t he y are rec or de d as s uc h i n t he e C R F a n d n o pre g na nc y f or m is t o be c o m plete d.
If a s u bject bec o mes pre g na nt after t he scree ni n g peri o d, t he I n vesti gat or is t o d o t he f oll o wi n g:
1.
T he s u bject d oes n ot nee d t o be wit h dra w n fr o m t he cli nical st u d y, i.e. s he ma y c o nti n ue t o 
atte n d t he pla n ne d st u d y visits, b ut n o i n vasi ve pr oce d ure s h o ul d be c o n d ucte d (e. g. n o sa m ple 
ta ke n f or la b test).
2.
C o m plete t he Pre g na nc y Re p ort Part A as f ull y as p ossi ble.  S e n d t he f or m wit hi n 2 4 h o urs of 
recei pt of t he i nf or mati o n t o t he Safet y  e-mail liste d a b o ve (a n d i n Secti o n 1 1. 9) .
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 5 3 of 8 7
3.
M o nit or a n d rec or d t he pr o gress of t he pre g na nc y  until its o utc o me.  If necessar y  an d a p pr o ve d 
b y t he s u bject or t heir le gal healt h care re prese ntati ve, co ntact t he s u bject’s re g ular p h y sicia n 
( ge neral practiti o ner or g y nec ol o gist) or h os pital staff t o o btai n f urt her details a n d as k f or 
re g ular f oll o w u p i nf or mati o n.
4.  
At t he o utc o me of t he pre g na nc y, c o m plete t he Pre g na nc y  Re p ort Part B. F or all t he a d diti o nal 
e val uati o ns, se n d t he f oll o w-u p i nf or mati o n t o t he Safet y e -mail wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n.  If t he s u bject ca n n o l o n ger be reac he d (l ost t o f oll o w-u p), d oc u me ntati o n of 
t he n o n- res p o nse/c o ntact wit h t w o p h o ne calls a n d a letter (certifie d wit h ret ur n recei pt) is 
re q uire d.
5.
If t he pre g na nc y lea ds t o a n a b orti o n (v ol u ntar y  a b orti o n, s p o nta ne o us a b orti o n or t hera pe utic 
a b orti o n), i n uter o deat h or c o n ge nital a n o mal y, f oll o w t he pr oce d ure f or declarati o n of a n 
S A E (see Secti o n 7. 2. 6. 2. 2 ).
7. 3
Ot her Assess me nts
7. 3. 1
P h ot o gr a p h y
Sta n dar dize d di gital p h ot o gra p hs will be ta ke n of t he s u bject’s lateral ca nt h us re gi o n a n d t he f ull 
face at baseli ne ( pri or t o treat me nt) a n d at eac h p ost -treat me nt visit.
Eac h In vesti gat or ( or desi g nee) will ta ke p h ot o gra p hs usi n g i de ntical ca mera e q ui p me nt, c o n diti o ns, 
a n d setti n gs. Detaile d i nstr ucti o ns f or p h ot o gra p h y  will be pr o vi de d i n a se parate p h ot o gra p h y 
ma n ual.
7. 3. 2
Pre g n a nc y Test
F or fe males of c hil d beari n g p ote ntial, a uri ne pre g na nc y test will be perf or me d pri or t o treat me nt at 
scree ni n g, baseli ne ( pri or t o treat me nt) a n d M o nt h 6 / E T. A ne gati ve pre g na nc y  test is re q uire d f or 
st u d y i ncl usi o n. T he res ult will be d oc u me nte d.
7. 4
A p pr o pri ate ness of M e as ure me nts
T he efficac y an d safet y m eas ure me nts use d i n t his st u d y are c o nsi dere d sta n dar d meas ure me nts, a n d 
are ge nerall y rec o g nize d as relia ble, acc urate, a n d rele va nt. T he L C L- I L A a n d L C L-S L A ha ve bee n 
de vel o pe d i n acc or da nce wit h F D A g ui da nce .
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 5 4 of 8 7
8.
C LI NI C A L S T U D Y VI SI T S D E S C RI P TI O N S A N D P R O C E D U R E S
8. 1
Descri pti o n of C li nic al St u d y V isits
Please refer t o t he Sc he d ule of Assess me nts Ta ble 2 .
A writte n, si g ne d I C F (i ncl usi ve of HI P A A a n d p h ot o c o nse nt) m ust be o btai ne d pri or t o perf or mi n g 
a n y cli nical st u d y-relate d e val uati o ns a n d/ or pr oce d ures. T he s u bject m ust be pr o vi de d wit h a f ull y 
c o m plete d, date d a n d si g ne d c o p y.
8. 1. 1
Scree ni n g/ Visit 1 (-1 4 d a ys t o D a y 0)
T he scree ni n g a n d baseli ne visits m a y  be perf or me d o n t he sa me d a y ; h o we ver, a ma xi m u m of 
1 4 da y s is all o we d bet wee n t he scree ni n g a n d b aseli ne visits . 
At t he scree ni n g visit, t he I n vesti gat or or desi g nee will:
1.
Re vie w a n d e x plai n t he nat ure of t he st u d y t o t he s u bject , partic ularl y t he pr o hi bite d acti vities 
a n d c o nstrai nts (e. g., restricti o ns f or ot her aest hetic treat me nts a n d t he use of t o pical a n d 
s yste mic me dicati o ns, see Secti o n 5. 4. 5 ).
2.
O btai n t he si g ne d a n d date d I CF (i ncl usi ve of HI P A A a n d p h ot o c o nse nt); pr o vi de a f ull y 
c o m plete d date d a n d si g ne d c o p y t o t he s u bject.
3.
C ollect i nf or mati o n re gar di n g de m o gra p hics (i.e., date of birt h, ge n der, race, et h nicit y, hei g ht, 
a n d wei g ht) , Fitz patric k s ki n t y pe, rele va nt me dical hist or y a n d c o nc urre nt diseases, pre vi o us 
facial treat me nts/ pr oce d ures (i ncl u di n g t o xi n naï ve/ n o n -t o xi n naï ve), pre vi o us me dicati o ns 
a n d pr oce d ures, a n d c o nc o mita nt me dicati o ns a n d pr oce d ures (see Ta ble 2 ).
4.
I nstr uct t he s u bject o n h o w t o c o m plete t he L C L -S L A at 
 ma xi m u m s mile. 
S u bject t o c o m plete self-assess me nt of bilateral L C L se verity at
ma xi m u m s mile p ositi o n usi n g t he 4- p oi nt P h ot o gra p hic Scale. B ilaterally s ym metrical L C L 
(Le vel 2 or Le vel 3 o n t he L C L- S L A) at ma xi m u m s mile,as assesse d b y  the s u bject,is re q uire d 
f or st u d y i ncl usi o n ( Secti o n 7. 1. 2 a n d A p pe n di x 2 ).
5.
I n vesti gat or t o c o m plete assess me nt of t he s u bject’s bilateral L C L  se verit y at
 
 ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale . M o derate t o se vere bilaterall y 
s ym metrical L C L (gra de 2 or 3 o n t he L C L- I L A) at ma xi m u m s mile, as assesse d b y  the 
I n vesti gat or, is re q uire d f or st u d y i ncl usi o n ( Secti o n 7. 1. 1 a n d A p pe n di x 1 ).
6.
I n vesti gat or t o p erf or m a foc use d P E (A p pe n di x
6 ). Rec or d a b n or mal fi n di n gs as me dical 
hist or y . Cli nicall y  si gnifica nt a b n or mal fi n di n gs are e xcl usi o nar y; d oc u me nt as scree n fail a n d 
d o n ot e nr olle d t he s u bject i n t he st u d y.
7.
If t he s u bject is a fe male of c hil d beari n g p ote ntial, c ollect uri ne f or U P T
a n d c om plete 
pre g na nc y  test (see la b orat or y ma n ual f or a d diti o nal pr oce d ures). D oc u me nt t he res ult. A 
ne gati ve res ult is re q uire d f or st u d y  i ncl usi o n.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 5 5 of 8 7
8.
Rec or d a n y A Es o n t he e C R F. A Es will be c ollecte d starti n g fr o m t he ti me of I nf or me d 
C o nse nt si g nat ure.
9.
Re vie w t he i ncl usi o n/e xcl usi o n criteria, a n d c o nfir m if s u bject meets 
st u d y eli gi bilit y
re q uire me nts. 
If yes, sc he d ule t he baseli ne visit.
If n o, d oc u me nt t he s u bject as a scree n fail ure.
1 0.
F or all s u bjects, enter t he s u bject i nf or mati o n i nt o t he e C R F; a SI N will be assi g ne d via t he 
e C R F s yste m.
8. 1. 2
B aseli ne / Visit 2 [D a y 0 ]
If t he scree ni n g a n d baseli ne visits are perf or me d as o n sa me d a y , o nl y  p erf or m st u d y assess me nts 
o nce (i.e., A E, c o nc o mita nt t hera pies/ pr oce d ures, U P T, P E, S L A, I L A, i ncl usi o n/e xcl usi o n re vie w).
A ma xi m u m of 1 4 da y s is all o we d bet wee n t he scree ni n g a n d baseli ne visits. 
At t he b aseli ne visit, t he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut A Es usi n g a n o pe n -e n de d q uesti o n, s uc h as “ Ha ve y o u n otice d a n y 
c ha n ge i n y o ur healt h si nce t he last visit?” Rec or d all e ve nts, as a p pr o priate .
2.
As k t he s u bject a b o ut a n y cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or c ha n ge d) si nce t he pre vi o us visit. Rec or d all c ha n ges.
3.
4.
5.
I nstr uct t he s u bject o n h o w t o c o m plete t he L C L- S L A at 
ma xi m u m s mile. 
S u bject t o c o m plete self-assess me nt of bilateral L C L se verity at
ma xi m u m s mile p ositi o n usi n g t he 4- p oi nt P h ot o gra p hic Scale. B ilaterally s ym metrical L C L 
(Le vel 2 or Le vel 3 o n t he L C L- S L A) at ma xi m u m s mile,as ass esse d b y  the s u bject,is re q uire d 
f or st u d y i ncl usi o n ( Secti o n 7. 1. 2 a n d A p pe n di x 2 ).
6.
I n vesti gat or t o c o m plete assess me nt of t he s u bject’s bilateral L C L  se verit y at 
 
 ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale . M o derate t o se vere bilaterall y 
s ym metri cal L C L (gra de 2 or 3 o n t he L C L- I L A) at ma xi m u m s mile, as assesse d b y  the 
I n vesti gat or, is re q uire d f or st u d y i ncl usi o n ( Secti o n 7. 1. 1 a n d A p pe n di x 1 ).
7.
8.
O btai n t he s u bject’s vital si g ns ( bl o o d press ure, heart rate, a n d res pirat or y rate). Vital si g ns 
are t o be ta ke n seate d after 1 0 mi n utes rest ( Secti o n 7. 2. 2 ). 
9.
O btai n 1 2- lea d E C G rec or di n g after t he s u bject has bee n resti n g i n a s u pi ne p ositi o n f or at 
least 1 0 mi n utes (Secti o n 7. 2. 3 ). 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 5 6 of 8 7
1 0.
If t he s u bject is a fe male of c hil d beari n g p ote ntial, c ollect uri ne f or U P T
a n d c o m plete 
pre g na nc y  test (see la b orat or y ma n ual f or a d diti o nal pr oce d ures). D oc u me nt t he res ult. A 
ne gati ve res ult is re q uire d f or st u d y  i ncl usi o n.
1 1.
C ollect bl o o d sa m ple (c he mistr y an d he mat ol o g y ) f or a nal ys is at t he ce ntral la b orat or y
( Secti o n 7. 2. 4 ).
1 2.
C ollect bl o o d sa m ple f or ne utralizi n g a nti b o d y testi n g ( Secti o n 7. 2. 5 ).
1 3.
Ta ke s u bject p h ot o gra p hs (refer t o p h ot o ma n ual f or c o m plete i nstr ucti o ns). If t he s u bject is 
weari n g ma ke -u p, i nstr uct t he s u bject t o re m o ve it pri or t o ta ki n g p h ot o gra p hs.
1 4.
I n vesti gat or t o perf or m a f oc use d P E (A p pe n di x 6 ). Cli nicall y  si gnif ica nt a b n or mal fi n di n gs 
are e xcl usi o nar y; d oc u me nt as scree n fail a n d d o n ot e nr olle d t he s u bject i n t he st u d y.
1 5.
Re vie w t he i ncl usi o n/e xcl usi o n criteria, a n d c o nfir m if s u bject meets 
st u d y eli gi bilit y 
re q uire me nts. 
If yes, e nr oll/ra n d o mize t he s u bject i n t he cli nical st u d y. Pr ocee d t o ne xt ste ps.
If n o, d oc u me nt t he s u bject as a scree n fail ure.
1 6.
F or all s u bjects, e nter a p pr o priate data i nt o t he e C R F; t he SI N s h o ul d ha ve bee n assi g ne d via 
t he e C R F sys te m at t he scree ni n g visit.
1 7.
F or s u bjects w h o meet all eli gi bilit y re q uire me nts, the I nvesti gat or or desi g nee will recei ve 
n otificati o n of t he s u bject’s kit n u m ber /ra n d o mizati o n assi g n me nt o nce all re q uire d data is 
e ntere d i nt o t he e C R F. T he I n vesti gat or or desi g nee s h o ul d pre pare t he assi g ne d treat me nt 
acc or di n gl y a n d c o m plete t he re q uire d d oc u me ntati o n a n d e C R F ( Secti o n 6. 1. 7 ). 
1 8.
Pri or t o i njecti o n, clea n t he s u bject’s treat me nt area wit h a s uita ble a ntise ptic s ol uti o n.
1 9.
T he In vesti gat or will a d mi nister t he assi g ne d treat me nt.  See Secti o n 6. 1. 7. 1 f or treat me nt 
pr oce d ure re q uire me nts. F oll o wi n g treat me nt a d mi nistrati o n, s u bjects will be m o nit ore d at t he 
st u d y ce nter f or 3 0 mi n utes ( Secti o n 6. 1. 7. 2 ). 
2 0.
O btai n t he s u bject’s p ost -treat me nt vital si g ns ( bl o o d press ure, heart rate, a n d res pirat or y rate). 
Vital si g ns are t o be ta ke n seate d after 1 0 mi n utes rest ( Secti o n 7. 2. 2 ). 
2 1.
2 2.
As k t he s u bject a b o ut A Es usi n g a n o pe n -e n de d q uesti o n. Rec or d all e ve nts, as a p pr o priate, 
o n t he c orres p o n di n g e C R F f or m(s).
2 3.
Rec or d p ost -treat me nt c o nc o mita nt t hera pies/ pr oce d ures .
2 4.
Sc he d ule t he ne xt visit ( Da y 7 ±1 da y ).
8. 1. 3
D a y 7 / Visit 3 (± 1 d a y)
T he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut A Es usi n g a n o pe n -e n de d q uesti o n, s uc h as “ Ha ve y o u n otice d a n y 
c ha n ge i n y o ur healt h si nce t he last visit? ” Rec or d all e ve nts, as a p pr o priate .
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 5 7 of 8 7
2.
As k t he s u bject a b o ut a n y cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or c ha n ge d) si nce t he pre vi o us visit. Rec or d all c ha n ges .
3.
 
4.
I nstr uct t he s u bject o n h o w t o c o m plete t he L C L- S L A at 
 ma xi m u m s mile. 
S u bject t o c o m plete self-assess me nt of bilateral L C L se verity at 
ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( Secti o n 7. 1. 2 a n d A p pe n di x 2 ).
5.
6.
7.
O btai n t he s u bject’s vital si g ns ( bl o o d press ure, heart rate, a n d res pirat or y rate). Vital si g ns 
are t o be ta ke n seate d after 1 0 mi n utes rest (Secti o n 7. 2. 2 ). 
8.
Ta ke s u bject p h ot o gra p hs (refer t o p h ot o ma n ual f or c o m plete i nstr ucti o ns). If t he s u bject is 
weari n g ma ke -u p, i nstr uct t he s u bject t o re m o ve it pri or t o ta ki n g p h ot o gra p hs.
9.
I n vesti gat or t o c o m plete assess me nt of t he s u bject’s bilateral L C L  se verit y at 
 
 ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( L C L-I L A) (Secti o n 7. 1. 1 a n d 
A p pe n di x 1 ).
1 0.
I n vesti gat or t o perf or m a f oc use d P E (A p pe n di x 6 ).
1 1.
Sc he d ule t he ne xt visit ( Da y  1 4 ± 3 d a y s).
8. 1. 4
D a y 1 4/ Visit 4 ( ± 3 d a y s)
T he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut A Es usi n g a n o pe n -e n de d q uesti o n, s uc h as “ Ha ve y o u n otice d a n y 
c ha n ge i n y o ur healt h si nce t he last visit? ” Rec or d all e ve nts, as a p pr o priate .
2.
As k t he s u bject a b o ut an y  cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or c ha n ge d) si nce t he pre vi o us visit. Rec or d all c ha n ges.
3.
I nstr uct t he s u bject o n h o w t o c o m plete t he L C L- S L A at
 ma xi m u m s mile. 
S u bject t o c o m plete self-assess me nt of bilateral L C L se verity at 
ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( Secti o n 7. 1. 2 a n d A p pe n di x 2 ).
4.
5.
6.
O btai n t he s u bject’s vital si g ns ( bl o o d press ure, heart rate, a n d res pirat or y rate). Vital si g ns 
are t o be ta ke n seate d after 1 0 mi n utes rest (Secti o n 7. 2. 2 ). 
7.
Ta ke s u bject p h ot o gra p hs (refer t o p h ot o ma n ual f or c o m plete i nstr ucti o ns). If t he s u bject is 
weari n g ma ke -u p, i nstr uct t he s u bject t o re m o ve it pri or t o ta ki n g p h ot o gra p hs.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 5 8 of 8 7
8.
I n vesti gat or t o c o m plete assess me nt of t he s u bject’s bilateral L C L  se verit y at 
 
 ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( L C L-I L A) ( Secti o n 7. 1. 1 a n d 
A p pe n di x 1 ).
9.
I n vesti gat or t o perf or m a f oc use d P E (A p pe n di x 6 ).
1 0.
Sc he d ule t he ne xt visit ( M o nt h 1
± 5 da y s).
8. 1. 5
M o nt h 1 / Visit 5 ( ± 5 d a y s)
T he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut A Es usi n g a n o pe n -e n de d q uesti o n, s uc h as “ Ha ve y o u n otice d a n y 
c ha n ge i n y o ur healt h si nce t he last visit? ” Rec or d all e ve nts, as a p pr o priate .
2.
As k t he s u bject a b o ut a n y cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or c ha n ge d) si nce t he pre vi o us visit. Rec or d all c ha n ges.
3.
I nstr uct t he s u bject o n h o w t o c o m plete t he L C L- S L A at
ma xi m u m s mile.
S u bject t o c o m plete self-assess me nt of bilateral L C L se verity at 
ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( Secti o n 7. 1. 2 a n d A p pe n di x 2 ).
4.
5.
6.
7.
8.
O btai n t he s u bject’s vital si g ns ( bl o o d press ure, heart rate, a n d res pirat or y rate). Vital si g ns 
are t o be ta ke n seate d after 1 0 mi n utes rest ( Secti o n 7. 2. 2 ). 
9.
O btai n 1 2- lea d E C G rec or di n g after t he s u bject has bee n resti n g i n a s u pi ne p ositi o n f or at 
least 1 0 mi n utes ( Secti o n 7. 2. 3 ).
1 0.
C ollect bl o o d sa m ple f or ne utralizi n g a nti b o d y testi n g ( Secti o n 7. 2. 5 ).
1 1.
Ta ke s u bject p h ot o gra p hs (refer t o p h ot o ma n ual f or c o m plete i nstr ucti o ns). If t he s u bject is 
weari n g ma ke -u p, i nstr uct t he s u bject t o re m o ve it pri or t o ta ki n g p h ot o gra p hs.
1 2.
I n vesti gat or t o c o m plete assess me nt of t he s u bject’s bilateral L C L  se verit y at
 
 ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( L C L-I L A) ( Secti o n 7. 1. 1 a n d 
A p pe n di x 1 ).
1 3.
I n vesti gat or t o perf or m a f oc use d P E (A p pe n di x 6 ).
1 4.
Sc he d ule t he ne xt visit ( M o nt h 2 ± 5 da y s).
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 5 9 of 8 7
8. 1. 6
M o nt hs 2 - 5/ Visit 6- 9 ( ±5 d a y s)
T he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut A Es usi n g a n o pe n -e n de d q uesti o n, s uc h as “ Ha ve y o u n otice d a n y 
c ha n ge i n y o ur healt h si nce t he last visit? ” Rec or d all e ve nts, as a p pr o priate .
2.
As k t he s u bject a b o ut a n y cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or c ha n ge d) si nce t he pre vi o us visit. Rec or d all c ha n ges.
3.
I nstr uct t he s u bject o n h o w t o c o m plete t he L C L- S L A at 
ma xi m u m s mile. 
S u bject t o c o m plete self-assess me nt of bilateral L C L se verity at
ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( Secti o n 7. 1. 2 a n d A p pe n di x 2 ).
4.
5.
6.
7.
Ta ke s u bject p h ot o gra p hs (refer t o p h ot o ma n ual f or c o m plete i nstr ucti o ns). If t he s u bject is 
weari n g ma ke -u p, i nstr uct t he s u bject t o re m o ve it pri or t o ta ki n g p h ot o gra p hs.
8.
I n vesti gat or t o c o m plete assess me nt of t he s u bject’s bilateral L C L  se verit y at 
 
 ma xi m u m s mile t he 4- p oi nt P h ot o gra p hic Scale ( L C L-I L A) ( Secti o n 7. 1. 1 a n d A p pe n di x 
1 ).
9.
Sc he d ule t he ne xt m o nt hl y visit ( ± 5 da y s).
8. 1. 7
M o nt h 6/ Visit 1 0 or E arl y Ter mi n ati o n visit ( ± 5 d a ys)
At t he Fi nal/ E T, t he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut A Es usi n g a n o pe n -e n de d q uesti o n, s uc h as “ Ha ve y o u n otice d a n y 
c ha n ge i n y o ur healt h si nce t he last visit? ” Rec or d all e ve nts, as a p pr o priate .
2.
As k t he s u bject a b o ut a n y cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or c ha n ge d) si nce t he pre vi o us visit. Rec or d all c ha n ges.
3.
I nstr uct t he s u bject o n h o w t o c o m plete t he L C L- S L A at 
 ma xi m u m s mile.
S u bject t o c o m plete self-assess me nt of bilateral L C L se verity at
ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( Secti o n 7. 1. 2 a n d A p pe n di x 2 ).
4.
5.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI
C CI
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 6 0 of 8 7
6.
7.
8.
O btai n t he s u bject’s vital si g ns ( bl o o d press ure, heart rate, a n d res pirat or y rate). Vital si g ns 
are t o be ta ke n seate d after 1 0 mi n utes rest ( Secti o n 7. 2. 2 ). 
9.
O btai n 1 2 -lea d E C G rec or di n g after t he s u bject has bee n resti n g i n a s u pi ne p ositi o n f or at 
least 1 0 mi n utes (Secti o n 7. 2. 3).
1 0.
C ollect bl o o d sa m ple (c he mistr y  a n d he mat ol o g y) f or a nalys is at t he ce ntral la b orat or y
( Secti o n 7. 2. 4 ).
1 1.
C ollect bl o o d sa m ple f or ne utralizi n g a nti b o d y testi n g ( Secti o n 7. 2. 5 ).
1 2.
Ta ke s u bject p h ot o gra p hs (refer t o p h ot o ma n ual f or c o m plete i nstr ucti o ns). If t he s u bject is 
weari n g ma ke -u p, i nstr uct t he s u bject t o re m o ve it pri or t o ta ki n g p h ot o gra p hs.
1 3.
If t he s u bject is a fe male of c hil d beari n g p ote ntial, c ollect uri ne f or U P T
a n d c o m plete 
pre g na nc y  test (see la b orat or y ma n ual f or a d diti o nal pr oce d ures). D oc u me nt t he res ult. 
1 4.
I n vesti gat or t o c o m plete assess me nt of t he s u bject’s bilateral L C L  se verit y at 
 
 ma xi m u m s mile usi n g t he 4- p oi nt P h ot o gra p hic Scale ( L C L-I L A) ( Secti o n 7. 1. 1 a n d 
A p pe n di x 1 ).
1 5.
I n vesti gat or t o perf or m a f oc use d P E (A p pe n di x 6 ).
1 6.
E xit t he s u bject fr o m t he st u d y .
8. 2
U nsc he d ule d Visits
W he n necessar y , u nsc he d ule d visits ma y  be c o n d ucte d, i n partic ular if a n A E occ urs a n d nee ds t o 
be assesse d a n d/ or treate d.
8. 3
S u bject I nstr ucti o ns
S u bjects will be a d vise d t hat a n y facial ma ke -u p will nee d t o be re m o ve d bef ore ta ki n g st u d y 
p h ot o gra p hs. 
S u bject s will als o be a d vise d of p ost-treat me nt care i nstr ucti o ns as o utli ne d i n Secti o n 6. 1. 7. 2 .
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI
C CI

C O N FI D E N TI A L
Pa ge 6 1 of 8 7
9.
S T A TI S TI C A L M E T H O D S P L A N N E D
9. 1
St atistic al a n d A n al ytic al P l a ns
A Statistical A nal y sis Pla n ( S A P) will be de vel o pe d as a se parate d oc u me nt. T he S A P will c o ntai n 
a m ore detaile d a n d tec h nical descri pti o n of s pecific data c o n ve nti o ns, calc ulati o ns a n d of statistical 
pr oce d ures f or e xec uti n g t he a nal ys es t hat are s pecifie d i n t he secti o ns of t he cli nical st u d y pr ot oc ol 
bel o w. T he S A P will be fi nalize d pri or t o data base l oc k .
A se parate S A P f or E U will be create d. T he E U S A P will i ncl u de a res p o n der defi niti o n f or t he 
pri mar y  e n d p oi nt acc or di n g t o t he E U re q uire me nt.
A n y  c ha n ge ma de t o t he fi nalize d S A P will be d oc u me nte d i n t he Cli nical St u d y  Re p ort ( C S R).
9. 1. 1
D at a T r a nsf or m ati o ns
F or a nti b o d y testi n g res ults, l o g tra nsf or mati o n mi g ht be use d as necessar y .
9. 1. 2
P o p ul ati o ns A n al yze d a n d E v al u a bilit y 
T he statistical a nal ys es will be perf or me d base d o n t he f oll o wi n g s u bject p o p ulati o ns.
9. 1. 2. 1
M o difie d I nte nt -t o-tre at ( mI T T) Effic acy P o p ul ati o n
T he m o difie d I nte nti o n-t o-treat ( mI T T) p o p ulati o n i ncl u des all s u bjects w h o are ra n d o mize d a n d 
dis pe nse d t he i n vesti gati o nal pr o d uct, a n d will be a nal yz e d acc or di n g t o t he ra n d o mizati o n sc he me; 
s u bjects wit h a p h ot o gra p hic a n d cate g orical scale M o nt h 1 assess me nt via a re m ote visit will be 
e xcl u de d fr o m t he mI T T. T he mI T T p o p ulati o n will be use d f or pri mar y  efficac y a nalys is. 
9. 1. 2. 2
I nte nt-t o-tre at (I T T) Effic acy P o p ul ati o n
T he I nte nti o n -t o-treat (I T T) p o p ulati o n i ncl u des all s u bjects w h o are ra n d o mize d a n d dis pe nse d t he 
i n vesti gati o nal pr o d uct, a n d will be a nal yze d acc or di n g t o t he ra n d o mizati o n sc he me. All sec o n dar y 
efficac y 
 varia bles will be a nal yze d base d o n t he I T T p o p ulati o n , as well as a 
se nsiti vit y a nalys is of t he pri mary efficac y  e n d p oi nt.
9. 1. 2. 3
Per -pr ot oc ol ( P P) Effic acy P o p ul ati o n
T he Per Pr ot oc ol ( P P) p o p ulati o n is a s u bset of t he m I TT s u bjects w h o ha ve n o pr ot oc ol de viati o ns 
t hat are c o nsi dere d t o ha ve a s u bsta ntial i m pact o n t he pri mar y  efficac y outc o me. If t he P P
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI

C O N FI D E N TI A L
Pa ge 6 2 of 8 7
p o p ulati o n c o ntai ns less t ha n 9 0 % of t he s u bjects i n m I TT, a se nsiti vit y anal ys is of t he pri mar y 
efficac y e n d p oi nt will be perf or me d base d o n t he P P p o p ulati o n.  
9. 1. 2. 4
S afety P o p ul ati o n
T he safety p o p ulati o n i ncl u des all s u bjects w h o were a d mi nistere d t he st u d y pr o d uct, a n d will be 
a nal yz e d acc or di n g t o as -treate d pri nci ple. All safet y data will be s u m marize d descri pti vel y  base d 
o n t he safet y p o p ulati o n.
9. 1. 2. 5
I m p ut ati o n of M issi n g D at a
T he O bser ve d Cases ( O C) will be use d f or all safety a nal ys es as well as t he sec o n dar y 
 
 efficac y a nal yses. T he pri mar y  efficac y a nal ys is will be perf or me d usi n g m ulti ple 
i m p utati o n ( MI), a n d re peate d usi n g baseli ne o bser vati o n carrie d f or war d ( B O C F) f or missi n g 
val ues. If dee me d necessar y , a ny a nal yses ma y be re peate d usi n g O C, B O C F, or MI  as a p pr o priate.
9. 1. 3
D at a P rese nt ati o n a n d G r a p hics
All statistical a nal ys es, i ncl u di n g s u m mar y ta bles a n d data listi n gs, will be perf or me d usi n g t he 
S A S ® s yste m ( versi o n 9).
All efficac y, safety a n d baseli ne c haracteristics varia bles will be prese nte d usi n g descri pti ve 
statistics wit hi n eac h treat me nt gr o u p, a n d gra p hs as a p pr o priate. C o nti n u o us data will be 
s u m marize d usi n g n ( n u m ber of o bser vati o ns), mea n, sta n dar d de viati o n, me dia n, mi ni m u m a n d 
ma xi m u m val ue, w hile cate g orical data will be prese nte d b y n a n d perce nta ges. All data will als o be 
liste d i n s u bject data listi n gs.
S u bject dis p ositi o n, c o m pleti o n a n d disc o nti n uati o n b y  st u d y visit, pr ot oc ol de viati o ns, 
de m o gra p hics a n d baseli ne c haracteristics, me dical hist or y , me dical a n d s ur gical pr oce d ures, pri or 
a n d c o nc o mita nt me dicati o ns, will be s u m marize d b y treat me nt gr o u p.
F or a nal ys is of d urati o n of res p o nse a n d ti me t o o nset of treat me nt res p o nse, Ka pla n -Meier pl ots 
a n d esti mates of t he me dia n e ve nt ti mes will be use d.
9. 1. 3. 1
S u b gr o u p A n alysi s
A nal y sis o n t he pr o p orti o n of c o m p osite res p o n ders at M o nt h 1 as meas ure d b y  the I L A a n d t he
S L A at ma xi m u m s mile will be perf or me d i n t he f oll o wi n g s u b gr o u ps:

Ge n der

Baseli ne se verit y gra de of t he I L A of L C L se verit y at ma xi m u m s mile

Pre vi o us treat me nt wit h B o N T - A

Fitz patric k s ki n t y pe
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 6 3 of 8 7
F or d urati o n of res p o nse, a s u b gr o u p a nal ysis usi n g o nl y s u bjects wit h at least 2 p oi nt i m pr o ve me nt 
o n t he L C L- I L A will be c o n d ucte d. T h us , d urati o n of res p o nse will be a nal yze d base d o n t he f ull 
I T T p o pulati o n as well as a s u b gr o u p a nal ys is.
9. 1. 3. 2
S afety A n alysis
All treat me nt relate d T E A Es b y  ma xi m u m i nte nsit y, treat me nt u nrelate d T E A Es b y  ma xi m u m 
i nte nsit y, treat me nt e mer ge nt S A Es b y  ca usalit y an d ma xi m u m i nte nsit y, a n d acti o n ta ke n of 
treat me nt relate d T E A E s will be s u m marize d b y S O C a n d P T i ncl u di n g n u m ber of s u bjects wit h at 
least o ne e ve nt, perce nta ges, a n d n u m ber of e ve nts. All relate d T E A Es will als o be s u m marize d b y 
ti me t o o nset a n d d urati o n. I n a d diti o n, a s h ort s u m mar y of t hese prese ntati o ns will be pr o vi de d.
A Es occ urri n g bef ore treat me nt will o nl y  be pr o vi de d i n s u bject data listi n gs.
Data f or he mat ol o g y , bl o o d c he mistr y, a nti b o dies, a n d vital si g ns will be s u m marize d b y  descri pti ve 
statistics wit h t he val ue at eac h visit as well as t he c ha n ge fr o m baseli ne. Res ults of E C Gs will be 
s u m marize d descri pti vel y. T he res ults of t he uri ne pre g na nc y  tests will be liste d.
9. 1. 4  
Wit h dr a w als a n d De vi ati o ns
All wit h dra w n s u bjects will be liste d i n di vi d uall y, i ncl u di n g at least s u bject n u m ber, date a n d reas o n 
f or wit h dra wal, a n d last visit perf or me d.
S u bjects wit h C S P de viati o ns will be liste d i n di vi d uall y, i ncl u di n g s u bject n u m ber a n d o bser ve d 
de viati o n. T he y  will als o be s u m marize d b y  st u d y ce nter a n d i n t otal ( b y treat me nt gr o u p a n d 
o verall). De pe n di n g o n t he seri o us ness of t he de viati o n, t he s u bject mi g ht be e xcl u de d fr o m t he P P 
p o p ulati o n, w hic h s hall be d oc u me nte d pri or t o data base l oc k.
9. 1. 5
I nfere nti al S t atistic al A n al yses
T he pri mar y  efficac y en d p oi nt will be a c o m p osite res p o n der rate base d o n t he L C L- I L A a n d 
L C L- S L A assess me nts of lateral ca nt hal li ne se verit y at ma xi m u m s mile at M o nt h 1. Res p o n der is
defi ne d as a s u bject w h o ac hie ves gra de /le vel 0 or 1 a n d at least 2 gra des i m pr o ve me nt fr o m baseli ne, 
o n b ot h scales c o nc urre ntl y. T he n ull h y p ot hesis of n o relati o ns hi p bet wee n treat me nt a n d res p o n der 
rate will be teste d a gai nst t he alter nati ve h y p ot hesi s t hat t here is a relati o ns hi p bet wee n treat me nt 
a n d res p o n der rate. T he res p o n der rates of t he Q M 1 1 1 4 -D P a n d place b o will t h us be c o m pare d usi n g 
C oc hra n -Ma ntel -Hae nszel 
test,
stratifie d 
b y
ce nter,
at 
5 % 
si g nifica nce 
le vel 
( 2-si de d). De pe n di n g o n t he n u m b er of ce nters, p o oli n g of ce nters mi g ht be nee de d. F or t he pri mar y 
efficac y en d p oi nt, c o nsiste nc y of t he res ults will be a nal yze d usi n g C oc hr a n-Ma ntel -Hae nszel test 
stratifie d b y  ge n der, baseli ne I L A, pri or use of b ot uli n u m t o xi n, a n d Fitz patric k s ki n t ype , 
res pecti vely.
T he a nal ys is of t he pri mar y efficac y en d p oi nt will be base d o n t he mI T T p o p ulati o n.  A se nsiti vit y 
a nal ys is of t he pri mar y  efficac y e n d p oi nt will be perf or me d usi n g t he I T T p o p ulati o n.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 6 4 of 8 7
F or t he sec o n dar y en d p oi nts, t he C oc hra n -Ma ntel -Hae nszel test will be use d t o c o m pare t he 
pr o p orti o n of s u bjects w h o ac hie ve 0 or 1 o n t he L C L -I L A at ma xi m u m fr o w n at M o nt h 1 a n d at all 
t he rest of t he p ost -treat me nt visits. T o c o ntr ol t he t ype I err or rate, t he fi xe d se q ue nce testi n g 
pr oce d ure will be use d, w hic h re q uires n o a dj ust me nt t o t he le vel of si g nifica nce. H o we ver t he 
c o m paris o ns m ust be ma de i n a pre -s pecifie d or der f oll o wi n g t he pr oce d ure o utli ne d bel o w:
1.
Pri mar y  a nalys is
Sec o n dar y  a nalys is:
2.
M o nt h 1
3.
D a y  1 4
4.
M o nt h 2
5.
M o nt h 3
6.
M o nt h 4
7.
M o nt h 5
8.
M o nt h
6
9.
D a y  7
If o ne of t he tests i n t he se q ue nce is n ot si g nifica nt ( p > 0. 0 5), n o c o nfir mat or y clai ms ca n be ma de 
base d o n tests f oll o wi n g (a n d i ncl u di n g) t hat o ne.
T he sec o n dar y anal y sis i n t he se q ue nce will be base d o n t he I TT p o p ulati o n wit h t he re m ote vis it 
assess me nts e xcl u de d. A se nsiti vit y anal ys is will be r u n usi n g t he I TT p o p ulati o n i ncl u di n g t he 
re m ote visit assess me nts.  
9. 2
S a m ple S ize D eter mi n ati o n
T he sa m ple size is deter mi ne d b y the n u m ber of s u bjects e x p ose d t o Q M 1 1 1 4 -D P i n t he L C L,  an d 
a m o u nt of l o n g- ter m safet y data. 
F urt her, d ue t o t h e p u blic healt h e mer ge nc y  relate d t o t he C O VID- 1 9 pa n de mic d uri n g 2 0 2 0, ste ps 
ha ve bee n ta ke n t o e ns ure patie nt a n d practiti o ner safety i n ali g n me nt wit h F D A G ui da nce date d 
Ma y  11, 2 0 2 0 ( G ui da nce o n C o n d uct of Cli nical Trials of Me dical Pr o d ucts d uri n g C O V I D-1 9 
P u blic Healt h E mer ge nc y). M ost n ota bl y, i n part ners hi p wit h cli nical sites a n d t he I RB, o pti o nal 
re m ote assess me nt pr oce d ures f or efficac y an d safet y en d p oi nts has bee n i m ple me nte d t o e ns ure 
safety a n d res pect l ocalize d a n d electi ve restricti o ns. H o w e ver, t he n u m ber of s u bjects i n t he mIT T 
p o p ulati o n use d i n t he assess me nt of t he pri mar y  efficac y en d p oi nt, s h o ul d still satisf y the sa m ple 
size re q uire me nts f or t he pri mar y efficac y a nalys is.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI

C O N FI D E N TI A L
Pa ge 6 5 of 8 7
9. 2. 3
S a m ple Si ze C alc ul ati o n
T he st u d y is pla n ne d t o i ncl u de a p pr o xi matel y 30 0 s u bjects, of w h o m 2 2 5 will be treate d wit h 
Q M 1 1 1 4 -D P a n d 7 5 s u bjects will recei ve place b o.
9. 2. 4 
I nteri m A n al ysis
N ot a p plica ble.  A n i nteri m a nal y sis is n ot pla n ne d f or t his st u d y.
1 0.
T R AI NI N G / M O NI T O RI N G / D A T A M A N A G E M E N T / Q U A LI T Y A S S U R A N C E
1 0. 1
Pers o n nel T r ai ni n g
In vesti gat ors a n d ot her res p o nsi ble pers o ns s h o ul d be liste d t o get her wit h t heir f u ncti o n o n t he 
si g nat ure a n d dele gati o n l o g. St u d y  staff s hall pr o vi de a c urric ul u m vitae or e q ui vale nt, as 
a p pr o priate.
It is t he res p o nsi bilit y of t he PI t o e ns ure t hat all pers o n nel i n v ol ve d i n t he st u d y are f ully i nf or me d 
of all rele va nt as pects of t he st u d y , i ncl u di n g detaile d k n o wle d ge of a n d d oc u me nte d trai ni n g i n all 
pr oce d ures t o be f oll o we d.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
C CI
C CI

C O N FI D E N TI A L
Pa ge 6 6 of 8 7
1 0. 2
Cli nic al M o nit ori n g
T he c o n d uct of t he cli nical st u d y will be cl osel y m o nit ore d b y  re prese ntati ves of t he S p o ns or t o 
verif y  a d here nce t o t he cli nical st u d y pr ot oc ol, I C H - G C P g ui deli nes, a n d a p plica ble SO Ps.  
T he I n vesti gat or will all o w t he C R O/ S p o ns or’s re prese ntati ves, t o ha ve direct access t o all cli nical 
st u d y rec or ds, C R Fs, c orres p o n di n g s u bject me dical rec or ds, st u d y pr o d uct (s) dis pe nsi n g rec or ds, 
a n d a n y ot her d oc u me nts c o nsi dere d s o urce d oc u me nta ti o n.  Ad diti o nall y , t he C R O/ S p o ns or 
re prese ntati ve is t o ha ve access t o t he st u d y pr o d uct st ora ge area a n d cli nical st u d y facilities.
T he I n vesti gat or als o a grees t o assist t he re prese ntati ve if re q uire d.
1 0. 3
D at a M a n a ge me nt
Data ma na ge me nt base d o n G C P refers t o t he acti vities defi ne d t o ac hie ve safe r o uti nes t o e nter 
cli nical data i nf or mati o n i nt o a data base, efficie ntl y an d a v oi di n g err ors. T he data ma na ge me nt 
r o uti ne i ncl u des pr oce d ures f or data base set- u p a n d ma na ge me nt, data e ntr y an d verificati o n, data 
vali dati o n, a n d d oc u me ntati o n of t he perf or me d acti vities i ncl u di n g i nf or mati o n of discre pa ncies i n 
t he pr ocess. T he data ma na ge me nt pr ocess will be descri be d i n detail i n t he data ma na ge me nt pla n 
( D M P).
T he data base, t he data e ntr y  scree ns a n d pr o gra m will be desi g ne d i n acc or da nce wit h t he C S P a n d 
C R F te m plate. Data vali dati o n will be perf or me d b y  co m p uterize d l o gical c hec ks a n d ma n ual 
re vie w. Dr u gs a n d e ve nts will be c o de d i n acc or da nce wit h W orl d Healt h Or ga nizati o n ( W H O) Dr u g 
a n d me dical dicti o nar y  for re g ulat or y acti vities ( Me d D R A) dicti o naries as s pecifie d i n t he D M P. 
Safet y  data ( S A E a n d if a p plica ble A E of s pecial i nterest) i n t he cli nical data base will be rec o ncile d 
a gai nst t he data i n t he safet y  data base.
W he n all eff orts ha ve bee n ma de t o e ns ure t hat t he data rec or de d i n t he e C R Fs a n d e ntere d i n t he 
data base is as c orrect a n d c o m plete as p ossi ble, t he cli nical data base will be l oc ke d. St u d y  data will 
be tra nsferre d t o S A S datasets, w hic h t hereafter will be write -pr otecte d. Statistical a nal ys es will be 
ge nerate d i n S A S usi n g data fr o m t he l oc ke d datasets.
1 0. 4
Q u alit y Ass ur a nce/ A u dit /I ns pecti o n
T he cli nical st u d y is c o n d ucte d u n der t he s p o ns ors hi p of t he S p o ns or i n c o m plia nce wit h t he 
a p plica ble i nter nati o nal a n d l ocal re g ulat or y re q uire me nts as well as a p plica ble I C H g ui deli nes a n d 
i n acc or da nce wit h t he S O Ps f or cli nical st u d y c o n d uct a n d m o nit ori n g fr o m t he S p o ns or a n d/ or t he 
C o ntract Researc h Or ga nizati o n ( C R O).
A u dits of cli nical st u d y ce nters m a y  be c o n d ucted b y  the S p o ns or/ C R O re prese ntati ves, a n d 
i ns pecti o n ma y  be perf or me d b y  Re g ulat or y Aut h orit y  ins pect orates or I RBs/I E Cs bef ore, d uri n g, 
or after t he cli nical st u d y.  
T he I n vesti gat or will all o w a n d assist t he C R O/ S p o ns or’s re prese ntati ves, I RBs/I E Cs a n d a n y 
re g ulat or y a ge nc y t o ha ve direct access t o all re q ueste d cli nical st u d y-relate d rec or ds.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 6 7 of 8 7
F or t he a u dits perf or me d b y, or o n be half of, t he S p o ns or a u dit ors, a u dit certificate(s) will be 
pr o vi de d b y Q ualit y Ass ura nce.
1 0. 5
C h a n ges i n C li nic al St u d y C o n d uct/ A me n d me nts
1 0. 5. 1
Cli nic al St u d y C o n d uct
Wit h t he e xce pti o n of eli mi nati n g a n i m me diate hazar d t o a s u bject, t he I n vesti gat or s h o ul d n ot 
de viate fr o m t he cli nical st u d y pr ot oc ol or i m ple me nt a n y c ha n ges wit h o ut writte n a p pr o val fr o m 
t he S p o ns or a n d pri or re vie w a n d d oc u me nte d a p pr o val/fa v ora ble o pi ni o n fr o m t he I RB/I E C of a 
pr ot oc ol a me n d me nt.
C ha n ges t hat i n v ol ve o nl y  lo gistical or a d mi nistrati ve c ha n ges t o t he cli nical st u d y pr ot oc ol are 
a ut h orize d.  The I n vesti gat or s h o ul d d oc u me nt a n d e x plai n a n y de viati o n fro m t he cli nical st u d y
pr ot oc ol.
1 0. 5. 2
A m e n d me nts
T he S p o ns or ma y  mo dif y  the cli nical st u d y pr ot oc ol at a n y ti me f or et hical, me dical, or scie ntific 
reas o ns. A ny a me n d me nts will be ha n dle d acc or di n g t o a p plica ble l ocal re g ulati o ns.
T he S p o ns or d oes n ot ha ve t o n o tif y no n -s u bsta ntial a me n d me nts t o t he c o m pete nt a ut h orities or t he 
Et hics C o m mittees. H o we ver, n o n- s u bsta ntial a me n d me nts s h o ul d be rec or de d a n d detaile d i n 
s u bse q ue nt s u b missi o ns e. g., i n t he s u bse q ue nt n otificati o n of a s u bsta ntial a me n d me nt.
1 1.
E T HI C S A N D G E N E R A L C LI NI C A L S T U D Y C O N D U C T C O N SI D E R A TI O N S
1 1. 1
I n de pe n de nt Et hics C o m mittee (I E C) or I nstit uti o n al Re vie w B o ar d (I R B)
T his cli nical st u d y pr ot oc ol a n d all a p plica ble a me n d me nts will be re vie we d a n d a p pr o ve d b y  the 
a p pr o priate I E Cs/IR Bs.
1 1. 2
Et hic al C o n d uct of t he Cli nic al St u d y
T his cli nical st u d y will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol , t he H E L SI N KI declarati o n 
( 1 9 6 4) a n d s u bse q ue nt a me n d me nts, a n d t he I C H G C P, a n d i n c o m plia nce wit h a p plica ble 
re g ulat or y re q uire me nts. 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 6 8 of 8 7
1 1. 3
S u bject Inf or m ati o n a n d C o nse n t
All s u bjects w h o partici pate i n t his cli nical st u d y are re q uire d t o be f ull y i nf or me d a b o ut t he cli nical 
st u d y i n acc or da nce wit h G C Ps g ui deli nes, fe deral re g ulati o ns, HI P A A , a n d g ui deli nes a n d i n 
acc or da nce wit h l ocal re q uire me nts.  
T he I C F (i ncl usi ve of HI P P A a n d p h ot o c o nse nt ), a p pr o ve d b y a n I R B/I E C, will be f ully e x plai ne d 
t o t he s u bject.  T he s u bject m ust a gree t o p h ot o c o nse nt i n or der t o partici pate i n t he cli nical st u d y. 
Pri or t o e nr ol lme nt i nt o t he cli nical st u d y, t he s u bject a n d t he PI or des i gn e e m ust si g n a n d date t he 
c o nse nt f or m(s).  The I nvesti gat or is res p o nsi ble f or mai ntai ni n g eac h s u bject’s c o nse nt f or m(s) i n 
t he I nvesti gat or’s site file a n d pr o vi di n g eac h s u bject wit h a c o p y of t he si g ne d a n d date d c o nse nt 
f or m(s).
1 1. 4
Pr otecti o n of Pers o n al D at a
T he c o m pleti o n of t he st u d y  i n v ol ves t he gat heri n g a n d pr ocessi n g of Pers o nal Data as s pecifie d i n 
t he Re g ulati o n ( E U) 2 0 1 6/ 6 7 9 o n t he pr otecti o n of i n di vi d uals wit h re gar d t o t he pr ocessi n g of 
pers o nal data a n d o n t he free m o ve me nt of s uc h d ata. F or t he p ur p oses of t he st u d y, S p o ns or will be 
c o nsi dere d t he Data C o ntr oller, a n d Pri nci pal I n vesti gat or a n d I nstit uti o n will b ot h be c o nsi dere d 
Data Pr ocess ors.
All pr ocessi n g of Pers o nal Data m ust be carrie d o ut i n acc or da nce wit h nati o nal le gislati o n 
c o ncer ni n g t he pr otecti o n of Pers o nal Data. T he I nstit uti o n a n d Pri nci pal I nvesti gat or are res p o nsi ble 
f or c o m pl yi n g wit h all re q uire me nts p urs ua nt t o nati o nal le gislati o n i n t he c o u ntr y in w hic h t he 
I nstit uti o n a n d Pri nci pal I n vesti gat or are locate d.
T he Pri nci pal I nvesti gat or u n dersta n ds t hat cli nical st u dies c o n d ucte d u n der a n I ND are e xe m pt fr o m 
t he st u d y su bject i de ntifier c o nfi de ntialit y pr o visi o ns of t he Healt h I ns ura nce P orta bilit y  a n d Access 
Act of 1 9 9 6 ( HIP A A), as pr o vi de d at C F R § 5 1 2 ( b)(iii), a n d t he st u d y su bject s h o ul d be ma de a ware 
of t his e xce pti o n i n t he i nf or me d c o nse nt. T he S p o ns or s hall, t o t he e xte nt feasi ble, pr otect st u d y 
s u bject i de ntifier i nf or mati o n.
T he I nstit uti o n a n d Pri nci pal I n vesti gat or are j oi ntl y res p o nsi ble f or o btai ni n g t he a p pr o priate 
i nf or me d c o nse nt of eac h s u bject f or t he pr ocessi n g of Pers o nal Data re q uire d i n or der t o c o m plete 
t he st u d y. S uc h c o nse nt s hall i ncl u de t he c o nse nt t o t he tra nsfer of Pers o nal Data t o g o ver n me nt 
a ut h orities l ocate d i n c o u ntries o utsi de t he U S. 
T he I nstit uti o n a n d Pri nci pal I nvesti gat or are j oi ntl y res p o nsi ble f or pr o vi di n g s ufficie nt i nf or mati o n 
t o all s u bjects t o e na ble t he m t o gi ve t heir i nf or me d c o nse nt n ot o nl y  to t he partici pati o n i n t he st u d y, 
b ut als o t o t he pr ocessi n g of Pers o nal Data. S uc h i nf or mati o n i ncl u des i nf or mati o n re gar di n g t he 
p ur p oses of t he pr ocessi n g, t he le n gt h of ti me d uri n g w hic h Pers o nal Data will be st ore d, t he ri g ht 
of access t o st ore d Pers o nal Data a n d t he ri g ht t o c orrecti o n or p ur gi n g of i nc orrect or o bs olete 
Pers o nal Data. A s u bject ma y als o wit h dra w his or her c o nse nt at a n y ti me d uri n g or after t he st u d y . 
A s u bject w h o wit h dra ws his or her c o nse nt t o t he pr ocessi n g of Pers o nal Data m ust be c o nsi dere d 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 6 9 of 8 7
t o ha ve wit h dra w n fr o m t he st u d y but t he data c ollecte d u ntil t he c o nse nt was wit h dra w n m a y  be 
use d i n t he statistical a nal y ses or t o c o m pl y  wit h le gal or a d mi nistrati ve re q uire me nts.
All c ollecti o n, pr ocessi n g a n d a nal yses of pr otecte d healt h i nf or mati o n, pers o nal data or si milar will 
be c o n d ucte d i n c om plia nce wit h a p plica ble l ocal, nati o nal a n d i nter nati o nal r ules, re g ulati o ns a n d 
g ui deli nes.
1 1. 5
C o ntr act u al R e q uire me nts
A c o ntract ual a gree me nt will be si g ne d bet wee n t he C R O/ S p o ns or a n d eac h I n vesti gat or/I nstit uti o n.  
T his d oc u me nt will c o ntai n s u p ple me ntar y inf or mati o n, i ncl u di n g fi na ncial ter ms, c o nfi de ntialit y, 
t he cli nical st u d y sc he d ule, t hir d party res p o nsi bilit y, a n d p u blicati o n ri g hts.
1 1. 6
D at a C ollecti o n a n d A rc hi vi n g
1 1. 6. 1
D at a C ollecti o n
T he I n vesti gat or m ust mai ntai n all re q uire d rec or ds f or all s u bjects.   Data f or t his cli nical st u d y will 
be rec or de d i n t he s u bject’s s o urce d oc u me nts a n d i n t he eC R Fs pr o vi de d b y t he S p o ns or.  All data 
s h o ul d be rec or de d in t he eC R Fs c o m pletel y a n d pr o m ptl y.
1 1. 6. 2
S o urce D oc u me nt ati o n
T he I nvesti gat or m ust kee p acc urate se parate rec or ds ( ot her t ha n t he eC R Fs) of all s u bject visits, 
bei n g s ure t o i ncl u de all perti ne nt cli nical st u d y-relate d i nf or mati o n.  A state me nt s h o ul d be ma de 
i n dicati n g t hat t he s u bjects ha ve bee n i ncl u de d i n t his cli nical st u d y a n d ha ve pr o vi de d si g ne d writt e n 
I nf or me d C o nse nt.  All A Es m ust be t h or o u g hly d oc u me nte d.
Res ults of a n y dia g n ostic tests c o n d ucte d d uri n g t he cli nical st u d y s h o ul d als o be i ncl u de d i n t he 
s o urce d oc u me ntati o n.  
1 1. 6. 3
Arc hi ves
All perti ne nt data, sa m ples, p h ot o gra p hs, c orres p o n de nce, a n d re p orts, t he ori gi nal or a me n de d 
cli nical st u d y pr ot oc ol, a n d all ot her material relati n g t o t he cli nical st u d y will be mai ntai ne d 
sec urely i n S p o ns or/ C R O/I n vesti gat or/I nstit uti o n arc hi ves f or t he le gall y re q uire d d urati o n f or 
arc hi vi n g.
T he I nvesti gat or/I n stit uti o n s h o ul d mai ntai n t he esse ntial cli nical st u d y d oc u me nts as s pecifie d i n 
Secti o n 8 of I C H -G C P, a n d acc or di n g t o t he a p plica ble re g ulat or y  re q uire me nts.
T he I nvesti gat or/I nstit uti o n s h o ul d ta ke meas ures t o pre ve nt acci de ntal or pre mat ure destr ucti o n of 
t hese d oc u me nts.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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C O N FI D E N TI A L
Pa ge 7 0 of 8 7
If t he Pri nci pal I n vesti gat or retires, rel ocates, or wit h dra ws fr o m t he res p o nsi bilit y of kee pi n g t he 
cli nical st u d y rec or ds f or a n y ot her reas o ns, c ust o d y m ust be tra nsferre d t o a pers o n w h o will acce pt 
t he res p o nsi bilit y.  The S p o ns o r/ C R O m ust be n otifie d i n writi n g of t he na me a n d a d dress of t he 
ne w c ust o dia n.
1 1. 7
I ns ur a nce
A certificate attesti n g T hir d Part y  c o vera ge of C R O/ S p o ns or will be pr o vi de d u p o n re q uest.
1 1. 8
P u blic ati o n P olic y
T he 
I nstit uti o n/ PI’s a n d t he S p o ns or’s o bli gati o ns re gardi n g i ntellect ual pr o pert y ri g hts, 
c o nfi de ntialit y, a n d p u blicati o ns are descri be d i n detail i n t he C T A.
T he ai m is t o s u b mit t he res ults of t his st u d y for p u blicati o n i n a p u blic data base (e. g., 
w w w. Cli nical Trials. g o v) a n d t o a me dical j o ur nal f or p u blicati o n of t he res ults. E ver y o ne w h o is t o 
be liste d as a n a ut h or of t he res ults of t his m ultice nter st u d y shall ha ve ma de a s u bsta ntial, direct, 
i ntellect ual c o ntri b uti o n t o t he w or k. A ut h ors hi p will be base d o n ( 1) s u bsta ntial c o ntri b uti o ns t o t he 
c once pti o n or desi g n of t he w or k; or t he ac q uisiti o n, a nal ys is, or i nter pretati o n of data f or t he w or k; 
a n d ( 2) drafti n g t he w or k or re visi n g it criticall y f or i m p orta nt i ntellect ual c o nte nt; a n d ( 3) fi nal 
a p pr o val of t he versi o n t o be p u blis he d; a n d ( 4) a gr ee me nt t o be acc o u nta ble f or all as pects of t he 
w or k i n e ns uri n g t hat q uesti o ns relate d t o t he acc urac y or i nte grit y of a n y part of t he w or k are 
a p pr o priatel y i n vesti gate d a n d res ol ve d.a C o n diti o ns 1, 2, 3, a n d 4 m ust all be met i n or der t o be 
desi g nate d as a ut h or. T h ose w h o d o n ot meet all f o ur criteria will be ac k n o wle d ge d. A m o n g t he 
a ut h ors t hat f ulfil t he a b o ve me nti o ne d criteria, o ne a ut h or will be a p p oi nte d b y t he S p o ns or t o ta ke 
pr i mar y res p o nsi bilit y f or t he o verall w or k as pri mar y a ut h or.
                                                
a Defi ni n g t he r ole of a ut h ors a n d c o ntri b ut ors, c o m pile d b y t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors 
(I C MJ E) ( htt p:// w w w.ic mje. or g).
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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1 1. 9
I n vesti g at or a n d A d mi nistr ati ve Str uct ure 
R ole
C o nt act I nf or m ati o n
S p o ns or C o ntact:
Me dical M o nit or:
Safet y  e-mail f or S A E, Pre g na nc y  
Re p orti n g , a n d P Q C:
E- mail: 
C R O:
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
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P P D
P P D
P P D

C O N FI D E N TI A L
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1 2.
S u m m ar y of C h a n ges i n Cli nic al St u d y Pr ot oc ol 4 3 Q M 1 9 0 1
1 2. 1
Pr ot oc ol Versi o n 3. 0 t o Versi o n 4. 0
Re m ote assess me nt pr oce d ures f or efficac y an d safet y en d p oi nts t o e ns ure safety a n d res pect 
l ocalize d a n d electi ve restricti o ns were i m ple me nte d d ue t o C O VI D - 1 9 pa n de mic. T heref ore, t he 
m o difie d I nte nti o n-t o-treat (mI T T ) efficac y p o p ulati o n is a d de d t o t he statistical a nal yses f or 
pri mar y  efficac y a nalys is. T his acti o n affect se veral secti o ns of t he Pr ot oc ol as s u m marize d bel o w.
Secti o n i n t he cli nic al 
st u d y pr ot oc ol
R ati o n al f or c h a n ges
Descri pti o n of c h a n ges
Secti o n 9. 1. 1, Data 
Tra nsf or mati o ns
Clarificati o n
 
 
Secti o n 9. 1. 2. 1, 
P o p ulati o ns A nal yze d 
a n d E val ua bilit y;
List of a b bre viati o ns a n d 
defi niti o ns of ter ms
D ue 
t o 
C O VI D - 1 9 
pa n de mic 
acti o ns.
T he mI T T
efficac y p o p ulati o n will 
be use d f or assess me nt of t he 
pri mar y efficac y e n d p oi nt. S u bjects 
wit h a p h ot o gra p hic a n d cate g orical 
scale M o nt h 
1 assess me nt via a 
re m ote visit will be e xcl u de d fr o m 
t he mI T T
M o difie d 
I nte nt-t o-treat 
( mI T T) 
Efficac y P o p ulati o n ad de d ( pri mar y 
efficac y a nal ysis) .
Secti o n 9. 1. 2. 2, I nte nt t o 
treat (I T T) Efficac y 
P o p ulati o n
D ue 
t o 
C O VI D - 1 9 
pa n de mic 
acti o ns .
T he mI T T p o p ulati o n will be use d f or 
pri mar y 
efficac y 
a nal ysis. 
A 
se nsiti vit y a nal ysis of t he pri mar y 
efficac y e n d p oi nt will be base d o n t he 
I TT p o p ulati o n.
Secti o n 9. 1. 2. 3, Per-
pr ot oc ol ( P P) Efficac y 
P o p ulati o n
Clarificati o n 
d ue 
t o C O VI D - 1 9 
pa n de mic acti o ns.
C ha n ge d fr o m “I T T” t o “ mI T T”
Secti o n 9. 1. 2. 5, 
I m p utati o n    of Missi n g 
Data
D ue 
t o 
C O VI D - 1 9 
pa n de mic 
acti o ns. 
A n i ncrease d n u m ber of dr o p -o uts/ 
missi n g data at M o nt h 1 visit.
Pri mar y i m p utati o n c ha n ge d t o “ MI” 
i nstea d of “ B O C F”.
Secti o n 9. 1. 5, I nfere ntial 
Statistical A nal yses
Clarificati o n 
d ue 
t o C O VI D - 1 9 
pa n de mic acti o ns.
A d de d:
“ T he a nal ysis of t he pri mar y efficac y 
e n d p oi nt will be base d o n t he mI T T 
p o p ulati o n.  A se nsiti vit y a nal ysis of 
t he pri mar y efficac y e n d p oi nt will be 
perf or me d usi n g t he I T T p o p ulati o n.”
“T he 
sec o n dar y 
a nal ysis 
i n t he 
se q ue nce will be base d o n t he I T T 
p o p ulati o n 
wit h 
t he re m ote visit 
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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4. 0
 
 
Pri nt date:
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C CI

C O N FI D E N TI A L
Pa ge 7 3 of 8 7
Secti o n i n t he cli nic al 
st u d y pr ot oc ol
R ati o n al f or c h a n ges
Descri pti o n of c h a n ges
assess me nts e xcl u de d. A se nsiti vit y 
a nal ysis will be r u n usi n g t he I TT 
p o p ulati o n i ncl u di n g t he re m ote visit 
assess me nts. ”  
Secti o n 9. 2 , Sa m ple Size 
Deter mi nati o n
Clarificati o n 
d ue 
t o C O VI D - 1 9 
pa n de mic acti o ns.
N o nee d t o i ncrease sa m ple size, b ut 
t he f oll o wi n g
clarificati o ns 
were 
ad de d:
“T he sa m ple size is deter mi ne d b y t he 
n u m ber 
of 
s u bjects 
e x p ose d 
t o 
Q M 1 1 1 4 -D P i n t he L C L , a n d a m o u nt 
of l o n g -ter m safet y data.”
“F urt her, d ue t o t he p u blic healt h 
e mer ge nc y relate d t o t he C O VI D -1 9 
pa n de mic d uri n g 2 0 2 0, ste ps ha ve 
bee n ta ke n t o e ns ure patie nt a n d 
practiti o ner safet y i n ali g n me nt wit h 
F D A G ui da nce date d Ma y 1 1, 2 0 2 0 
( G ui da nce o n C o n d uct 
of Cli nical 
Trials of Me dical 
P r o d ucts d uri n g 
C O VI D - 1 9 
P u blic 
Healt h 
E mer ge nc y). 
M ost 
n ota bl y, 
i n 
part ners hi p wit h cli nical sites a n d t he 
I R B, o pti o nal 
re m ote assess me nt 
pr oce d ures f or efficac y a n d safet y 
e n d p oi nts has bee n i m ple me nte d t o 
e ns ure safet y a n d res pect l ocalize d a n d 
electi ve
restricti o ns. H o we ver, 
t he 
n u m ber of s u bjects i n t he mI T T 
p o p ulati o n use d i n t he assess me nt of 
t he pri mar y efficac y e n d p oi nt, s h o ul d 
still 
satisf y 
t he 
sa m ple 
size 
re q uire me nts f or t he pri mar y efficac y 
a nal ysis. ”
Secti o n 1 2: Secti o n 1 2. 1
Pr ot oc ol A me n d me nt
A d de d Secti o n: S u m mar y of C ha n ges 
Pr ot oc ol versi o n 3. 0 t o versi o n 4. 0
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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C O N FI D E N TI A L
Pa ge 7 4 of 8 7
1 3.
LI T E R A T U R E R E F E R E N C E LI S T
1.
I C H E 6: I nter nati o nal C o nfere nce o n Har m o nisati o n Tri partite G ui deli ne:  G ui deli ne f or G o o d Cli nical 
Practice. 1 9 9 6 
2.
S u n dara m, H., M. Si g n ori ni, S . Lie w, A. R. Tri n da de de Al mei da, Y. W u, A. Vieira Braz, S. Fa gie n, G. 
J. G o o d ma n, G. M o n heit, H. Ras pal d o a n d G. Gl o bal Aest hetics C o nse ns us ( 2 0 1 6). " Gl o bal Aest hetics 
C o nse ns us: B ot uli n u m T o xi n T y pe A --E vi de nce -Base d Re vie w, E mer gi n g C o nce pts, a n d C o nse ns us 
Rec o m me n dati o ns f or Aest hetic Use, I ncl u di n g U p dates o n C o m plicati o ns." Plast Rec o nstr S ur g 
1 3 7( 3): 5 1 8e -5 2 9e.
3.
A wa n, K. H. ( 2 0 1 7). " T he t hera pe utic usa ge of b ot uli n u m t o xi n ( B ot o x) i n n o n -c os metic hea d a n d nec k 
c o n diti o ns - A n e vi de nce base d re vie w." Sa u di P har m J 2 5( 1): 1 8 - 2 4.
4.
Sc ott A B.
B ot uli n u m t o xi n i njecti o n i nt o e xtra oc ular m uscles
as a n alter nati ve t o stra bis m us
s ur ger y. O p ht hal m ol o g y.  
1 9 8 0; 8 7: 1 0 4 4- 9.
5.
M o n heit, G. D. a n d A. Pic kett ( 2 0 1 7). " A b o b ot uli n u mt o xi n A: A 2 5 -Year Hist or y." Aest het S ur g J 
3 7(s u p pl _ 1): S 4 -s 1 1.
6.
Dressler, D., S. V o gt a n d F. Sa beri ( 2 0 1 6). " Der Off -La bel Use a m Beis piel der B ot uli n u mt o xi n -
T hera pie." Kli nisc he Ne ur o p h ysi ol o gie 4 7( 0 2): 8 7 - 9 1.
7.
L u p o, M. P. ( 2 0 1 6). " T o x O utsi de t he B o x: Off -La bel Aest hetic Uses of B ot uli n u m T o xi n." J Dr u gs 
Der mat ol 1 5( 9): 1 1 5 1 - 1 1 5 7.
8.
Ca m pa nati, A., E. Marti na, K. Gi uli o d ori, V. C o nsales, I. B o b yr a n d A. Offi da ni ( 2 0 1 7). " B ot uli n u m 
T o xi n Off -La bel Use i n Der mat ol o g y: A Re vie w." S ki n A p pe n d a ge Dis or d 3( 1): 3 9 - 5 6.
9.
Carr ut hers, J. a n d A. Carr ut hers ( 2 0 0 7). " T he e v ol uti o n of b ot uli n u m ne ur ot o xi n t y pe A f or c os metic 
a p plicati o ns." J C os met Laser T her 9( 3): 1 8 6 - 1 9 2.
1 0. Rza n y, B., D. Dill -M uller, D. Gra bl o witz, M. Hec k ma n n, D. Cair d a n d G. Ger ma n -A ust ria n 
Retr os pecti ve St u d y ( 2 0 0 7). " Re peate d b ot uli n u m t o xi n A i njecti o ns f or t he treat me nt of li nes i n t he 
u p per face: a retr os pecti ve st u d y of 4, 1 0 3 treat me nts i n 9 4 5 patie nts." Der mat ol S ur g 3 3( 1 S pec N o.): 
S 1 8 - 2 5.
1 1. Pirazzi ni, M., O. R ossett o, R. Ele o pra a n d C. M o ntec ucc o ( 2 0 1 7). " B ot uli n u m Ne ur ot o xi ns: Bi ol o g y, 
P har mac ol o g y, a n d T o xic ol o g y." P har mac ol Re v 6 9( 2): 2 0 0 - 2 3 5.
1 2. I nvesti gat ors Br oc h ure Q M 1 1 1 4 -D P ( B ot uli n u m Ne ur ot o xi n T y pe A) U p per Facial Wri n kles, e diti o n 5.
1 3. P usic A L, Klasse n A F, Sc ott A M, Ca n o SJ. De vel o p me nt a n d ps yc h o metric e val uati o n of t he F A C E -Q 
satisfacti o n wit h a p peara nce scale: a ne w patie nt-re p orte d o utc o me i ntrs u me nt f or facial aest hetic 
patie nts. Cli n Plast S ur g 2 0 1 3; 4 0( 2): 2 4 9 - 2 6 0
1 4. Klasse n A F, Ca n o SJ, Sc ott A M, P usi c A L. Meas uri n g o utc o mes t hat matter t o face -lift patie nts: 
de vel o p me nt a n d vali dati o n of F A C E -Q a p peara nce a p praisal scales a n d a d verse affects c hec klist f or 
t he l o wer face a n d nec k. Plast Rec o nstr S ur g 2 0 1 4; 1 3 3( 1): 2 1- 3 0
1 5. I C H E 2 A: I nt er n ati o n al C o nf er e n c e o n H ar m o nis ati o n Tri p artit e G ui d eli n e:  Cli ni c al S af et y D at a 
M a n a g e m e nt: D efi niti o ns a n d Sta n dar ds f or E x pe dite d Re p orti n g. 1 9 9 4
1 6. F D A G ui d a n c e for I n d ustr y. U p p er F a ci al Li n es: d e v el o pi n g b ot uli n u m t o xi n dr u g pr o d u cts ( dr aft), 
2 0 0 4.
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
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1 4.
A P P E N DI C E S
A p pe n di x 1
V ali d ate d I n vesti g at or 4- p oi nt P h ot o gr a p hic Sc ale of L ater al C a nt h al Li ne
Se verit y ( L C L-I L A)
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C CI

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Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
Pa ge 7 7 of 8 7
A p pe n di x 2
V ali d ate d S u bject 4- p oi nt P h ot o gr a p hic Sc ale of L ater al C a nt h al Li ne
Se verit y ( L C L-S L A)
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
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Title  
D o c i d  
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M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
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Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
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Title  
D o c i d  
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M A- 4 0 3 7 0
 
 
 
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Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
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Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
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Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
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C O N FI D E N TI A L
Pa ge 8 4 of 8 7
A p pe n di x 6
F oc use d P h ysic al E x a mi n ati o n F or m E x a m ple
N ot d o n e  
     Pr o vi d e d et ails: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Ge ner al He alt h Assess me nt : C o m plete at Scree ni n g, B aseli ne ( pri or t o tre at m e nt), D a y 7, D a y 1 4, M o nt hs 1 , a n d 
6/ E T
Q uesti o n t he s u bject a b o ut t heir ge neral healt h ( ge neral well bei n g/ b o dil y f u ncti o ns, e. g., ar ms, le gs, st o mac h/ bla d der/ 
b o w el, als o refer t o t he list of A d verse E ve nts P ote ntiall y S u g gesti ve of  Dista nt S prea d of T o xi n (A p pe n di x 7) . 
A b n or m alities n ote d pre -i njecti o n s h o ul d be rec or de d as me dical hist or y a n d I n vesti gat or s h o ul d c o nfir m if a n y 
a b n or malities affect s u bject eli gi bilit y. A b n or malities n ote d p ost -i njecti o n s h oul d be d oc u me nte d as A Es.
Ne xt, pr ocee d t o t he F oc use d P h ysical E xa mi nati o n ( Part 1 a n d 2) as i n dicate d bel o w .
P art 1: C o m plete at Scree ni n g, B aseli ne ( pri or t o tre at me nt), D a y 7, D a y 1 4, M o nt hs 1 , a n d 6/ E T
Please perf or m a tar gete d e xa mi nati o n of t he fa ce, hea d, a n d nec k rec or di n g a b n or malities. 
P art 1 E x a m i n ati o n
N o r m al
A b n or m al * ( pr o vi de det ails)
E y eli d p ositi o n
E y e br o w p ositi o n
Visi o n a b n or malities ( n ot 
refracti ve err ors)
T hr oat f u ncti o n (e. g., 
s wall o wi n g/ dri n k water)
A bilit y t o tal k a n d c he w
A bilit y t o stic k o ut a n d m o ve 
t o n g ue
A bilit y t o lift s h o ul ders 
* A b n or m al fi n di n gs at t he scree ni n g a n d b aseli ne visit, n ote d pre- i njecti o n, s h o ul d be rec or de d as me dic al 
hist or y a n d t he I n vesti g at or s h o ul d c o nfir m if a n y a b n or m alities affect s u bject eli gi bilit y.  A b n or m alities n ote d 
after st u d y tre at m e nt s h o ul d be d oc u me nte d as A E .
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
I n vesti g at or Si g n at ure
D ate
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 8 5 of 8 7
P A R T 2: C o m plete at D a y 7, D a y 1 4 , M o nt hs 1 , a n d 6/ E T
N ot d o n e  
     Pr o vi d e d et ails: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
After q uesti o ni n g t he s u bject a b o ut t heir ge neral healt h a n d perf or mi n g Part 1, deter mi ne if t here are a n y cli nic all y 
si g nific a nt a b n or malities t h at ma y s u g gest l ocal or re m ote s prea d of t o xi n effect.
-
L ocal S prea d of T o xi n Effect refers t o effects i n areas a djace nt t o t he treat me nt area ( e. g., l o wer fr o ntalis, 
gla bellar area, me dial part of te m p oralis).
-
Re m ote S prea d of T o xi n Effect refers t o effects i n ot her b o d y parts, n ot a djace nt t o t he treat me nt area, w he n 
effect ca n o nl y be attri b ute d t o t he t o xi n a n d t here is n o ot her m e dic all y s o u n d c a use.
-
Deter mi ne if t he e ve nt is cli nicall y si g nifica nt ( i.e., wo ul d affect s u bject safet y, c o nf o u n d t he st u d y data, or 
re q uires me dical treat me nt) a n d d oc u me nt o n t he s o urce d oc u me nt.
Please refer t o t he list of re m ote s prea d of t o xi n e ve nts (A p pe n di x 7 ) w hile d oi n g cli nical e val uati o ns base d o n s u bject’s 
s y m pt o ms a n d si g ns. Directe d q uesti o ni n g a n d e xa mi nati o n will t he n be perf or me d as a p pr o priate. If ye s, please 
descri be.
P art 2 E x a m i n ati o n
N o
Yes * ( pr o vi de det ails)
T ar gete d P h ysic al E x a mi n ati o n of F ace a n d 
Nec k t o E v al u ate L oc al S pre a d of T o xi n 
Effect
L ocal s prea d of t o xi n effect e ve nt(s) 
o bser ve d?
Ge ner al P h ysic al E x a mi n ati o n t o E v al u ate 
t he R e m ote S pre a d of T o xi n Effect
Re m ote s prea d of t o xi n effect e ve nt(s) 
o bser ve d? 
* A b n or m alities s h o ul d be d oc u m e nte d as A E.
A d diti o n al c o m me nts f or F oc use d P h ysic al E x a m: 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
I n vesti g at or Si g n at ure
D ate
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 8 6 of 8 7
A p pe n di x 7
A d verse E ve nts P ote nti all y S u g gesti ve of Re m ote S pre a d of T o xi n
T he f oll o wi n g a d verse e ve nts ma y p ote ntiall y  be s u g gesti ve of re m ote s prea d of t o xi n (base d o n F D A 
G ui da nce f or I n d ustr y: U p per Facial Li nes: De vel o pi n g B ot uli n u m T o xi n Dr u g Pr o d ucts; A u g ust 
2 0 1 4). 1 6
acc o m m o dati o n dis or d er
e yeli d f u ncti o n dis or der
paresis cra nial ner ve
A refle xia
e yeli d pt osis
peri p heral ner ve pals y
A s pirati o n
facial pals y
peri p heral paral ysis
bl urre d visi o n
facial paresis
pel vic fl o or m uscle wea k ness
B ot ulis m
f o urt h cra nial ner ve paresis
p ne u m o nia as pirati o n
Bra d ycar dia
he mi paresis
p u pillar y refle x i m paire d
b ul bar pals y
h y p o gl ossal ner ve paresis
q ua dri paresis
C o nsti pati o n
h y p orefle xia
res pirat or y arrest
cra nial ner ve palsies
h y p ot o nia
res pirat or y de pressi o n
cra nial ner ve paral ysis
m o n o paresis
res pirat or y distress
dia p hra g matic paral ysis
m usc ular wea k ness
res pirat or y fail ure
D i pl o pia
ne ur o m usc ular t o xicit y
res pirat or y paral ysis
dr y m o ut h
paral ysis
s peec h dis or der
D ysart hria
paral ysis flacci d
t hir d cra nial ner ve paresis
D ys p ha gia
paral ysis rec urre nt lar y n geal ner ve
tri ge mi nal ner ve paresis
D ys p h o nia
paral ytic ile us
uri nar y rete nti o n
D ys p nea
para paresis
v ocal c or d paral ysis
e xtra oc ular m uscle paresis
paresis
v ocal c or d paresis
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

C O N FI D E N TI A L
Pa ge 8 7 of 8 7
SI G N E D A G R E E M E N T O F T H E C LI NI C A L S T U D Y P R O T O C O L
C T N:
4 3 Q M 1 9 0 1
C S P title:
A M ultice nter, Ra n d o mize d, D o u ble- Bli n d, Place b o -C o ntr olle d St u d y  
t o E val uate t he Efficac y a n d Safety of Q M 1 1 1 4 -D P f or t he Treat me nt 
of M o derate t o Se vere Lateral Ca nt hal Li nes ( R E A D Y - 2)
I, t he u n dersi g ne d, ha ve rea d a n d u n dersta n d t he C S P s pecifie d a b o ve, a n d a gree o n t he c o nte nts. 
T he C S P, t he cli nical trial a gree me nt ( C T A) a n d t he a d diti o nal i nf or mati o n gi ve n i n t he 
I n vesti gat or’s Br oc h ure (I B) will ser ve as a basis f or c o -o perati o n i n t his st u d y .
Pri nci p al I n vesti g at or
Pri nte d na me 
Si g nat ure
Date
St u d y ce nter
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3

Si g n p a g e: 1 of 1
S I G N A T U R E S PA G E
D at e
Si g n e d b y
2 0 2 0- 0 6- 1 0 0 7: 5 1
J u stifi c ati o n
A p pr o v e d b y T e c h ni c al E x p ert
2 0 2 0- 0 6- 1 0 0 8: 4 2
J u stifi c ati o n
A p pr o v e d b y T e c h ni c al E x p ert
2 0 2 0- 0 6- 1 0 1 1: 3 6
J u stifi c ati o n
C o m pil e d b y
2 0 2 0- 0 6- 1 1 0 8: 0 3
J u stifi c ati o n
A p pr o v e d b y O w n er
Title  
D o c i d  
4 3 Q M 1 9 0 1 Cli nic al St u d y Pr ot oc ol - Q M 1 1 1 4 -  L C L
M A- 4 0 3 7 0
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 0- 0 6- 1 0 1 1: 3 8
4. 0
 
 
Pri nt date:
 2 0 2 0- 0 6- 1 1 1 3: 0 3
P P D
P P D
P P D
P P D