A Phase 2, Double-masked, Randomized, Vehicle-controlled Study of VVN461 Ophthalmic Solution in Treating Post -Operative Ocular Inflammation in Subjects Undergoing Routine Unilateral Cataract Surgery
Phase: PHASE2
Conditions: Inflammation
Sponsor: VivaVision Biotech, Inc

NCT06164743  
Clinical Study VVN461-CS201  
Protocol  
13 February 2024 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1  of 5 9  
T itl e Pa g e  
A  p h as e 2, d o u bl e -m as k e d, r a n d o mi z e d, v e hi cl e -c o nt r oll e d st u d y of 
V V N 4 6 1 O p ht h al mi c S ol uti o n i n t r e ati n g p ost -o p e r ati v e o c ul a r 
i nfl a m m ati o n i n s u bj e cts u n d e r g oi n g r o uti n e u nil at e r al c at a r a ct 
s u r g e r y 
Pr ot oc ol N u m ber : 
V V N 4 6 1 -C S -2 0 1  
N ati o n al Cli nic al Tri al N u m ber:  
N C T 0 6 1 6 4 7 4 3  
I n vesti g ati o n al Ne w Dr u g N u m ber:  
1 6 6 9 2 7  
St u d y  P h ase : 
2  
S p o ns or:  
Vi va Visi o n Bi otec h ( H o n g K o n g) L t d. 
U nit 2 0 2 A of t he 2 n d Fl o or of B uil di n g 2 E  
P hase O ne, H o n g K o n g Scie nce Par k  
H o n g K o n g, 0 0 0 0 0 0, C hi na  
Me dic al M o nit or :  
 
 
 
 
 
Versi o n N u m ber:  
4. 0  
Iss ue D ate : 
1 3 Fe br uar y 2 0 2 4  
 
 
C o nfi de nti alit y St ate me nt  
T his d oc u me nt c o ntai ns i nf or mati o n fr o m  Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  a n d is of c o nfi de ntial, tra de secret, 
a n d/ or pr o prietar y nat ure a n d ma y n ot be discl ose d u nless s uc h discl os ure is re q uire d b y fe deral or state la w or 
re g ulati o n. It is l oa ne d t o y o u f or y o ur c o nfi de ntial re vie w o n be half of Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d. o nl y 
a n d is n ot t o be p h ot oc o pie d, discl ose d, or tra ns mitte d t o a n y ot her pers o n or part y wit h o ut t he a d va nce writte n 
a p pr o val of  Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2  of 5 9  
P r ot o c ol S y n o psis  
Title:  
A  p hase 2, d o u ble -mas ke d, ra n d o mize d, ve hicle -c o ntr olle d st u d y of V V N 4 6 1 
O p ht hal mic S ol uti o n i n treati n g p ost -o perati ve oc ular i nfla m mati o n i n s u bj ects 
u n der g oi n g r o uti ne u nilateral cataract s ur ger y  
P h ase:  
2  
Desi g n/ C o n d uct:  
T his is a m ultice nter, d o u ble -mas ke d, ra n d o mize d, ve hicle -c o ntr olle d, parallel -
c o m paris o n st u d y c o n d ucte d at sites i n t he U nite d States ( U S) i n s u bj ects 
u n der g oi n g r o uti ne u nilateral cataract e xtracti o n a n d le ns re place me nt ( C E L R) 
s ur ger y via p hac oe m ulsificati o n 
O bjecti ves:  
P ri m ar y:  
E val uate t he oc ular efficac y of 2 differe nt d oses of V V N 4 6 1 O p ht hal mic 
S ol uti o n i n treati n g p ost -o p erati ve oc ular i nfla m mati o n ass ociate d 
wit h 
cataract s ur ger y c o m pare d wit h t he oc ular efficac y of a matc hi n g V e hicle  
Sec o n d ar y:  
E val uate t he safet y of  V V N 4 6 1  
E n d p oi nts:  
P ri m ar y E n d p oi nt : 
 
P r o p orti o n of s u bj ects wit h a nteri or c ha m ber cell ( A C C) Gra de 0 i n 
the st u d y e ye at Visit 6 ( Da y 1 4)  
Sec o n d ar y E n d p oi nt s: 
 
Pr o p orti o n of s u bj ects wit h A C C Gra de 0  i n t he st u d y e ye at Visit 5 
( Da y 7) 
 
Pr o p orti o n of s u bj ects wit h a nteri or c ha m ber flare ( A C F) Gr a de 0 i n 
t he st u d y e ye at Visit 6 ( Da y 1 4) 
 
Pr o p orti o n of s u bj ects wit h A C F  Gra de 0 i n t he st u d y e ye at Visit 5 
( Da y 7) 
 
P r o p orti o n of s u bj ects re q uiri n g resc ue me dicati o n bef ore Visit 6 
( Da y 1 4) 
E x pl or at or y E n d p o i nts: 
 
M ea n c ha n ge fr o m baseli ne ( C F B) i n A C C Gra de i n t he st u d y e ye at 
eac h visit  
 
Mea n C F B i n A C F Gra de i n t he st u d y e ye at eac h visit  
 
Pr o p orti o n of s u bj ects wit h n o p ost -o perati ve oc ular pai n i n t he st u d y 
e ye at Visit 6 ( Da y 1 4)  
 
Pr o p orti o n of s u bj ects w it h n o p ost-o perati ve oc ular pai n i n t he st u d y 
e ye at Visit 5 ( Da y 7)  
P o p ul ati o n St u die d:  
A p pr o xi matel y 9 0 c o m plete d s u bj ects ( 3 0 per gr o u p)  w h o ha ve u n der g o ne 
ro uti ne u nilateral C E L R s ur ger y via p hac oe m ulsificati o n wit h o ut s ur gical 
c o m plicati o n.  
S u bj ects w h o meet all i ncl usi o n criteria will be eli gi ble f or st u d y  partici pati o n.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3  of 5 9  
I ncl usi o n Criteri a:  
1.  ≥2 1 years of a ge a n d i n g o o d ge neral healt h at Visit 1 ( Scree ni n g)  
2.  Willi n g a n d a ble t o pr o vi de i nf or me d c o nse nt a n d pr o vi de rele va nt 
pri vac y a ut h orizati o n(s)  
3.  Willi n g a n d a ble t o c o m pl y wit h st u d y re q uire me nts a n d visit sc he d ule  
4.  Clear oc ular me dia ( ot her t ha n cataract) i n t he st u d y e ye  
5.  P la n ni n g t o 
u n der g o r o uti ne 
u nilateral 
C E L R 
s ur ger y 
via 
p hac oe m ulsificati o n e xtracti o n a n d i m pla ntati o n of a n i ntra o c ular 
le ns. All o w e d i n t he st u d y e ye at Visit 2 ( Da y of S ur ger y): 
a. 
Li m bal rela xi n g i ncisi o ns (las er -assiste d a n d n o n -laser) 
b.  I ntraca meral i nj ecti o ns 
a n d i ntraca meral 
me dicati o ns, 
e xcl u di n g t h ose i de ntifie d i n E xcl usi o n Criteri o n # 2  
6.  A t Visit 1 ( Scree ni n g), has t he p ote ntial, i n t he o pi ni o n of t he 
I n vesti gat or, for p ost o perati ve best c orrecte d vis ual ac uit y ( B C V A ) 
≤0 . 2 L o garit h m of t he Mi ni m u m A n gle of Res ol uti o n ( L o g M A R) 
(i.e., 2 0/ 3 2 S nelle n or better) i n t he st u d y e ye as assesse d usi n g Earl y 
Treat me nt Di a betic Reti n o pat h y St u d y ( E T D R S)  
7.  A t Visit 1 ( Scree ni n g), has B C V A ≤1. 0 L o g M A R (i.e., 2 0/ 2 0 0 
S nelle n) i n t he n o n -st u d y e ye d ue t o pat h ol o g y ot her t ha n cataract  as 
assesse d usi n g E T D R S  
8.  A ble t o self -a d mi nister e ye dr o ps  
9.  At Visit 3 ( Baseli ne/ Ra n d o mi zati o n; Da y  1), has A C C  Gra de  ≥2 i n 
t he st u d y e ye 
S u bj ects w h o meet a n y of t he f oll o wi n g e xcl usi o n criteria will n ot be eli gi ble 
f or st u d y partici pati o n.  
E xcl usi o n Criteri a : 
O p ht h al mic ( Eit her E ye)  
1.  A n y oc ular pai n at Visit 1 ( Scree ni n g)  
2.  Use d wit hi n 1 wee k bef ore Visit 2 ( Da y of S ur ger y), or be pla n ni n g 
t o use d uri n g t he st u d y, cortic oster oi ds, oral or t o pical n o n -ster oi dal 
a nti -i nfla m mat or y dr u gs ( N S AI Ds), or  O mi dria ®  (i.e., p he n yle p hri ne 
a n d ket or olac i nj ecti o n) .  
N o te: L o w-d ose acet ylsalic yli c aci d (i.e., ba b y a s piri n or si milar) is 
all o we d  
3.  M o derate t o se vere li d, c o nj u ncti val, or c or neal fi n di n gs at Visit 1 
( Scree ni n g) 
4.  C or neal a b n or malit y (e. g., str o mal, e pit helial, 
or e n d ot helial 
d ystr o p hies, i ncl u di n g e pit heli al base me nt me m bra ne d ystr o p h y)  
5.  Hist or y of c hr o nic/ rec urre nt i nfla m mat or y e ye disease (e. g., scleritis, 
a n y u veitis, her pes keratitis)  
6.  A n y si g ns of i ntra oc ular i nfla m mati o n (cell/flare) at 
Visit 1 
( Scree ni n g)  
7.  I ntra oc ular press ure (I O P) ≥2 4 m m H g at Visit 1 ( Scree ni n g)  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4  of 5 9  
O p ht h al mic ( St u d y E ye)  
8.  Usi n g  or u n willi n g t o f or g o c o ntact le ns use wit hi n defi ne d wi n d o ws 
bef ore Visit 2 ( Da y of S ur ger y) a n d f or t he d urati o n of t he st u d y  
a. 
P ol y met h yl met hacr ylate c o ntact le nses ( 6 m o nt hs bef ore 
s ur ger y a n d t hr o u g h o ut st u d y) 
b.  Gas per mea ble ri gi d le nses ( 1 m o nt h bef or e s ur ger y a n d 
t hr o u g h o ut st u d y)  
c. 
E xte n de d wear or dail y s oft le nses ( 7 da ys bef ore s ur ger y a n d 
t hr o u g h o ut st u d y)  
9.  K n o w n pat h ol o g y t hat ma y affect vis ual ac uit y, partic ularl y reti nal 
c ha n ges t hat affect visi o n (e. g., 
mac ular de ge nerati o n, c yst oi d 
mac ular e de ma, pr oliferati ve dia betic reti n o pat h y)  
1 0.  Ca ps ule or z o n ular a b n or malities wit h pre -o perati ve cr ystalli ne le ns 
tilt or dece ntrati o n (e. g., Marfa n’s s y n dr o me) or a b n or malities t hat 
ma y affect p ost -o perati ve ce ntrati o n or tilt of t he cr ystalli ne l e ns (e. g.,  
pse u d oe xf oliati o n s y n dr o me)  
1 1.  Hist or y of m o derate t o se vere oc ular tra u ma wit h t he p ossi bilit y of 
pre vi o us z o n ule de hisce nce  
1 2.  O c ular or peri oc ular s ur gical i nter ve nti o ns wit hi n defi ne d wi n d o ws  
bef ore Vi sit 1 ( Scree ni n g) 
a. 
Micr oi n vasi ve gla uc o ma s ur ger y, a n y i n cisi o nal oc ular 
s ur ger y, or i ntraca meral dr u g de p ot t o l o wer I O P (a n y 
hist or y)  
b.  I ntra oc ular s ur ger y ( 6 m o nt hs) 
c. 
Laser s ur ger y, li m bal rela xi n g i ncisi o n pr oce d ure, e yeli d 
s ur ger y ( 3 m o nt hs) 
1 3.  P u pil a b n or malities (e. g., n o n -reacti ve, t o nic p u pils, a b n or mall y 
s hape d p u pils, p u pils t hat d o n ot dilate at least 3. 5 m m u n der 
mes o pic/sc ot o pic c o n diti o ns)  
1 4.  Kerat oc o n us or si g nifica nt irre g ular asti g matis m o n pre -o perati ve 
oc ular t o p o gra p h y  
1 5.  Ha ve a c o n diti o n, or be i n a sit uati o n, t hat ma y p ut t he s u bj ect at 
si g nifica nt risk of c o m ple x s ur ger y a n d s ur gical c o m plicati o ns t hat 
w o ul d lea d t o wit h dra wal fr o m t he st u d y  
O p ht h al mic ( N o n -st u d y E ye) 
1 6.  U n der we nt c ataract s ur ger y < 1 4 da ys bef ore Visit 1 ( Scree ni n g) or, 
d uri n g t he st u d y, will re q uire cataract s ur ger y < 1 da y after Visit 2 
( Da y of S ur ger y) 
Ge ner a l 
1 7.  W it hi n 3 0 da ys bef ore 
Visit 1 ( Scree ni n g), partici pate d in a n 
i n vesti gati o nal dr u g or de vice st u d y, or ha ve use d a n i n vesti gati o nal 
dr u g or de vic e 
1 8.  A ller g y or h y perse nsiti vit y t o t he i n vesti gati o nal pr o d uct (I P) or its 
e xci pie nts  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5  of 5 9  
1 9.  S ig nifica nt s yste mic disease (e. g., u nc o ntr olle d dia betes ; m yast he nia 
gra vis ; he patic, re nal, car di o vasc ular , or e n d ocri ne dis or ders)  
2 0.  U nc o ntr olle d s yste mic disease, defi ne d as, wit hi n 3 0 da ys  bef ore V isit 
1 ( Scree ni n g), a c ha n ge i n disease stat us or me dicati o ns t hat ma y p ut 
t he s u bj ect at i ncrease d ris k or c o nf o u n d i nter pretati o n of st u d y res ults 
2 1.  C ha n ges wit hi n 3 0 da ys  bef ore V isit 1 ( Scree ni n g), or a ntici pate d 
c ha n ges d uri n g t he st u d y, t o t he d osa ge of s yste mic me dicati o n t hat 
c o ul d ha ve a s u bsta ntial effect  o n I O P  
2 2.  K n o w n blee di n g te n de ncies  
2 3.  Ac ute or c hr o nic disease or ill ness t hat w o ul d p ut t he s u bj ect at 
i ncrease d ris k or c o nf o u n d i nter pretati o n of st u d y res ults (e. g., 
a ut oi m m u ne disease, c o n necti ve tiss ue disease, i m m u n o deficie nc y, 
s us pecte d gla uc o ma, gla uco mat o us c ha n ges i n t he f u n d us or vis ual 
fiel d, oc ular i nfla m mati o n, etc.) 
2 4.  R e q uires,  is li kel y t o re q uire, or is u n willi n g t o disc o nti n ue t he use of 
pr o hi bite d me dicati o ns  
2 5.  P re g na nt, n ursi n g, or pla n ni n g a pre g na nc y d uri n g t he st u d y 
2 6.  U n willi n g or u na ble t o us e a n acce pta ble met h o d of c o ntr ace pti o n 
t hr o u g h o ut t he st u d y if a w o ma n of c hil d beari n g p ote ntial ( W O C B P) 
2 7.  U n willi n g or u na ble t o use a n acce pta ble met h o d of c o ntr ace pti o n 
t hr o u g h o ut t he st u d y if a male se x ual part ner of a W O C B P 
I n vesti g ati o n al Pr o d ucts:  
 
V V N 4 6 1, 1. 0 %  
 
V V N 4 6 1, 0. 5 %  
 
Ve hicle  
D osi n g Re gi me n:  
A p pr o xi matel y 9 0 c o m plete d s u bj ects will be ra n d o mize d i n a 1: 1: 1 rati o t o 
V V N 4 6 1, 1. 0 %, V V N 4 6 1, 0. 5 %, or a matc hi n g Ve hicle t hat d oes n ot c o ntai n 
t he acti ve p har mace utical i n gre die nt ( A PI). S u bj ects will a d mi nister 1 e ye dr o p 
i n t he st u d y e ye f o ur ti mes a d a y ( QI D) f or 1 4 da ys. 
Assess me nts/ E v al u ati o ns:  
E ffic ac y: 
 
Oc ular i nfla m mati o n ( Sta n dar dizati o n of 
U veitis 
N o me nclat ure 
[ S U N] Scale) 
 
P ost -o perati ve oc ular pai n ( N u meric P ai n Rati n g Scale [ N P R S])  
S afet y:  
 
A d verse e ve nt ( A E) m o nit ori n g ( oc ular a n d n o n -oc ular)  
 
Cli nicall y rele va nt c ha n ges fr o m baseli ne i n t he f oll o wi n g:  
o  
B C V A  
o  
Slit la m p bi o micr osc o p y  
o  
I O P 
o  
Dilate d o p ht hal m osc o p y  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 6  of 5 9  
D ur ati o n of St u d y:  
S u bj ects will be assesse d at 7 visits o ver a p pr o xi matel y 8 wee k s. 
Visits 
will i ncl u de a scree ni n g visit, t he da y of cat aract s ur ger y, a 
baseli ne/ra n d o mizati o n visit, a n d efficac y a n d safet y e val uati o n visits after 3, 
7, a n d 1 4 da ys of QI D d osi n g wit h I P i n t he st u d y e ye. T he st u d y will c o ncl u de 
wit h a safet y f oll o w -u p v isit a p pr o xi matel y 1 wee k after t he e n d of t he pla n ne d 
d osi n g peri o d.  
St atistic al M et h o ds:  
A  sa m ple size of a p pr o xi matel y 9 0 c o m plete d s u bj ects will be ra n d o mize d i n 
a 1: 1: 1 rati o t o V V N 4 6 1, 1. 0 %, V V N 4 6 1, 0. 5 %, a n d a mat c hi n g Ve hicle t hat 
d oes n ot c o ntai n  t he A PI. Wit h a sa m ple size i n eac h gr o u p of 3 0, t he st u d y 
will ha ve 8 0 % p o wer t o detect a differe nce of 3 5 %, ass u mi n g a res p o nse rate 
of 3 0 % i n t he Ve hicle gr o u p, a n d a t w o -si de d 0. 0 5 si g nifi ca nce le vel f or a 
P ears o n c hi -s q uare test. A dr o p-o ut rate of 1 0 % is ass u me d, res ulti n g i n a t otal 
sa m ple size of a p pr o xi matel y 1 0 2 s u bj ects. 
T he F ull A nal ysis Set ( F A S) will c o nsist of all s u bj ects w h o are ra n d o mize d. 
S u bj ects will be a nal yze d i n t he gr o u p t o w hic h t he y are ra n d o mize d. T his set 
will b e use d f or t he a nal ysis of all efficac y e n d p oi nts as t he pri mar y a nal ysis.  
T he P er Pr ot oc ol ( P P) A nal ysis Set is a s u bset of t he F A S a n d will i ncl u de all 
s u bj ects i n t he F A S w h o c o m plete st u d y-re q uire d treat me nt a n d w h o f oll o w 
t he pr ot oc ol wit h o ut si g nifica nt de viati o ns. T he deter mi nati o n of si g nifica nt 
pr ot oc ol de viati o ns will be ma de bef ore data b ase l oc k a n d u n mas ki n g.  
T he S afet y A nal ysis Set ( S A F) will i ncl u de all s u bj ects w h o recei ve at least 
o ne d ose of I P, as i n dicate d o n t he d osi n g rec or d. S u bj ects will be a nal yze d  i n 
t he gr o u p acc or di n g t o t he treat me nt recei ve d. All safet y varia bles will be 
a nal yze d usi n g t he S A F, a n d o nl y o bser ve d data will be i ncl u de d (i.e., missi n g 
data will re mai n missi n g f or t he safet y a nal ysis).  
Pri m ar y Esti m a n d : T he pri mar y esti ma n d is treat me nt differe nce bet wee n 
V V N 4 6 1 ( 1. 0 % or 0. 5 %) a n d t he Ve hicle i n t he pr o p orti o n of s u bj ects wit h 
A C C  Gra de 0  at Visit 6 ( Da y 1 4) i n t he st u d y e ye usi n g t he F A S.  
T ar g et P o p ul ati o n : S u bj ects u n der g oi n g r o uti ne cataract s ur ger y w h o m eet 
t he st u d y e ntr y criteria. 
E n d p oi nt : Pr o p orti o n of s u bjects wit h A C C Gra de 0  i n t he st u d y e ye at Visit 
6 ( Da y 1 4).  
Tre at me nt 
C o n diti o n(s) : Treat me nt c o n diti o n is base d o n ra n d o mize d 
treat me nt. 
P o p ul ati o n -le vel S u m m ar y: T he differe nce i n pr o p orti o ns i n s u bj ects wit h 
A C C  Gra de 0  i n t he st u d y e ye at Visit 6 ( Da y 1 4) a n d t he c orres p o n di n g  
p -val ue.  
T he pr o p ose d pr oce d ures t o ha n dle missi n g data a n d i nterc urre nt e ve nts are as 
f oll o ws: 
 
Disc o nti n uati o n of st u d y t her a p y wit h c o nti n ue d partici pati o n i n t he 
st u d y wit h o ut recei pt of resc ue t hera p y 
o  
Treat me nt P olic y A p pr oac h –  n o i m p utati o n; use o bser ve d 
data  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 7  of 5 9  
 
Recei pt of resc ue t hera p y (t o pical c ortic oster oi d) i n t he st u d y e ye  
o  
C o m p osite A p pr oac h –  s u bj ects w h o recei ve resc ue t hera p y 
at or bef ore t he assess me nt visit will be ass u me d t o ha ve 
faile d t he pri mar y e n d p oi nt 
 
Missi n g data wit h or wit h o ut wit h dra wal, re gar dless of reas o n  
o  
H y p ot hetical A p pr oac h –  n o i m p utati o n; a nal ysis will be 
base d o n s u bj ects w h o ha ve a n e val ua ble a nteri or c ha m ber  
in t he st u d y e ye at Visit 6 ( Da y 1 4)  
P ears o n’s c hi -s q uare will be use d t o test t he pri mar y e n d p oi nt bet wee n t he 2 
differe nt d oses of V V N 4 6 1 v ers us t he Ve hicle. T he pri mar y a nal ysis will als o 
be perf or me d o n t he P P A nal ysis Set.  
T he sec o n dar y efficac y e n d p oi nts will i ncl u de t he pr o p orti o n of s u bj ects wit h 
A C C  G ra de 0, t he pr o p orti o n of s u bj ects wit h A C F Gra de 0, a n d t he pr o p orti o n 
of s u bj ects re q uiri n g resc ue me dicati o n. T hese e n d p oi nts will be a nal yze d 
re gar dless of t he si g nifica nce of t he pri mar y e n d p oi nt a nal ysis. 
E x pl orat or y e n d p oi nts will be a nal yze d i n a ma n ner si milar t o t he sec o n dar y 
e n d p oi nts. Mea n C F B  i n A C C Gra de a n d A C F Gra de will be a nal yze d usi n g 
mi xe d m o del re peate d meas ur es. T he m o del will i ncl u de treat me nt, visit, a n d 
treat me nt b y visit i nteracti o n as fi xe d effects a n d a c o variate f or baseli ne 
meas ure me nt ( w here a p pr o priate) 
wit h a ra n d o m effect f or site. 
A n 
u nstr uct ure d c o varia nce a m o n g re peate d meas ure me nts will be ass u me d. O nl y 
data fr o m bef ore t he use of resc ue me dicati o n will be i ncl u de d i n t hese 
anal yses. T he pr o p orti o n of s u bj ects wit h n o p ost -o perati ve oc ular pai n i n t he 
st u d y e ye at Visit 5 ( Da y 7) a n d Visit 6 ( Da y 1 4) will als o be a nal yze d.  
Safet y a nal yses will be perf or me d o n all s u bj ects i n t he S A F. T he assess me nt 
of safet y will be base d o n t he s u m mar y of oc ular a n d n o n -oc ular A Es, B C V A, 
a n d o p ht hal mic e xa mi nati o ns  usi n g slit la m p bi o micr os c o p y a n d dilate d 
o p ht hal m osc o p y. S u m maries will be pr o vi de d b y treat me nt gr o u p a n d, f or 
oc ular assess me nts, se paratel y b y e ye.  
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 8  of 5 9  
T a bl e of C o nt e nts  
1  
I ntr o d ucti o n ......................................................................................................................... 1 2  
1. 1  Bac k gr o u n d  ....................................................................................................................... 1 2  
1. 2  St u d y R ati o nale  ................................................................................................................. 1 3  
1. 3  Ris k/ Be nefit Assess me nt  .................................................................................................. 1 3  
1. 3. 1  K n o w n P ote ntial Ris ks  .............................................................................................. 1 3  
1. 3. 2  K n o w n P ote ntial Be nefits  ......................................................................................... 1 3  
1. 3. 3  Assess me nt of Be nefits a n d Ris ks  ............................................................................ 1 4  
2  
St u d y O bjecti ves a n d E n d p oi nts ........................................................................................ 1 5  
3  
St u d y Desi g n  ........................................................................................................................ 1 6  
3. 1  O verall Desi g n of t he St u d y  .............................................................................................. 1 6  
3. 2  Rati o nale f or t he St u d y Desi g n  ......................................................................................... 1 7  
3. 3  D ose J ustificati o n  .............................................................................................................. 1 7  
3. 4  E n d of St u d y Defi niti o n  .................................................................................................... 1 8  
4  
St u d y P o p ul ati o n  ................................................................................................................. 1 9  
4. 1  I n cl usi o n Criteria .............................................................................................................. 1 9  
4. 2  E x cl usi o n Criteria  ............................................................................................................. 1 9  
4. 3  Scree n Fail ures  .................................................................................................................. 2 1  
5  
St u d y Tre at me nt(s) or I nter ve nti o n(s)  .............................................................................. 2 2  
5. 1  I n v esti gati o nal Pr o d ucts .................................................................................................... 2 2  
5. 1. 1  Descri pti o n  ................................................................................................................ 2 2  
5. 1. 2  D osa ge a n d A d mi nistrati o n ....................................................................................... 2 2  
5. 2  Pre parati o n/ St ora ge/ H a n dli n g/ Acc o u nt a bilit y  .................................................................. 2 3  
5. 2. 1  Ac q uisiti o n a n d Acc o u nt a bilit y  ................................................................................ 2 3  
5. 2. 2  Pr o d uct F or m ulati o n, A p peara n ce, Pac ka gi n g, a n d La b eli n g  ................................... 2 3  
5. 2. 3  Pr o d uct St ora ge a n d Sta bilit y .................................................................................... 2 3  
5. 3  Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Mas ki n g  .............................................. 2 4  
5. 4  D osi n g A d h ere n ce a n d D osi n g Diar y  ............................................................................... 2 4  
5. 4. 1  D osi n g A d h ere n ce  ..................................................................................................... 2 4  
5. 4. 2  D osi n g Diar y  ............................................................................................................. 2 4  
5. 5  Pri or a n d C o nc o mita nt T hera p y  ........................................................................................ 2 4  
5. 5. 1  Pr o hi bite d Me dicati o ns a n d Pr oce d ures  .................................................................... 2 5  
5. 5. 2  Resc ue Me dic ati o n  .................................................................................................... 2 6  
6  
St u d y Disc o nti n u ati o n/ S u bject Wit h dr a w al  ..................................................................... 2 7  
6. 1  Disc o nti n uati o n of I n v esti gati o nal Pr o d uct  ...................................................................... 2 7  
6. 2  S u bject Disc o nti n uati o n/ Wit h dra wal fr o m t he St u d y  ....................................................... 2 7  
6. 3  L ost t o F oll o w -U p  ............................................................................................................. 2 7  
7  
St u d y Pr oce d ures  ................................................................................................................ 2 9  
7. 1  Visit Descri pti o ns .............................................................................................................. 2 9  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 9  of 5 9  
7. 1. 1  Visit 1 ( Scree ni n g; Da y -3 0 t o Da y -1)  ..................................................................... 2 9  
7. 1. 2  Visit 2 ( Da y of S ur ger y; Da y 0)  ................................................................................ 2 9  
7. 1. 3  Visit 3 ( Baseli ne/ Ra n d o mizati o n; Da y 1)  ................................................................. 3 0  
7. 1. 4  Visit 4 ( Da y 3 ± 1)  .................................................................................................... 3 0  
7. 1. 5  Visit 5 ( Da y 7 ± 1)  .................................................................................................... 3 1  
7. 1. 6  Visit 6 ( E n d of Treat me nt; Da y 1 4 ± 2)  .................................................................... 3 1  
7. 1. 7  Visit 7 ( E n d of St u d y; Earl y T er mi nati o n; Da y 2 1 ± 2)  ........................................... 3 2  
7. 1. 8  U nsc he d ule d Visits  ................................................................................................... 3 2  
7. 1. 9  Earl y Ter mi nati o n  ..................................................................................................... 3 2  
8  
St u d y Assess me nts  .............................................................................................................. 3 3  
8. 1  Efficac y E val uati o ns  ......................................................................................................... 3 3  
8. 2  Safet y E val uati o ns  ............................................................................................................ 3 3  
8. 2. 1  A d verse E v e nts a n d Seri o us A d verse E v e nts  ........................................................... 3 3  
8. 2. 2  Heart Rate, Bl o o d Press ure, a n d Ot her Safet y E v al uati o ns  ...................................... 3 7  
9  
St atistic al C o nsi der ati o ns  ................................................................................................... 3 8  
9. 1  Statistical H y p ot hesis  ........................................................................................................ 3 8  
9. 2  Sa m ple Siz e Deter mi nati o n ............................................................................................... 3 8  
9. 3  A nal ysis P o p ulati o ns  ......................................................................................................... 3 9  
9. 4  Statistical A nal yses  ........................................................................................................... 3 9  
9. 4. 1  Baseli ne Descri pti ve A nal yses  .................................................................................. 3 9  
9. 4. 2  Efficac y A nal yses  ..................................................................................................... 4 0  
9. 4. 3  Safet y A nal yses  ......................................................................................................... 4 1  
9. 5  I nteri m A nal ysis ................................................................................................................ 4 2  
9. 6  S u b gr o u p A n al ys es  ........................................................................................................... 4 2  
9. 7  E x pl orat or y A nal yses  ........................................................................................................ 4 2  
9. 8  Missi n g, U n use d, or S p uri o us Data  .................................................................................. 4 2  
9. 9  Ta b ulati o n of I n di vi d ual S u bject Data  .............................................................................. 4 2  
1 0  S u p p orti n g D oc u me nt ati o n a n d O per ati o n al C o nsi der ati o ns  ........................................ 4 3  
1 0. 1  
Re g ulat or y Iss ues, Et hical C o ncer ns, a n d St u d y O versi g ht  .......................................... 4 3  
1 0. 1. 1  
I nf or me d C o nse nt Pr ocess .................................................................................... 4 3  
1 0. 1. 2  
St u d y Disc o nti n uati o n a n d Cl os ure  ...................................................................... 4 4  
1 0. 1. 3  
C o nfi de ntialit y a n d Pri vac y  .................................................................................. 4 4  
1 0. 1. 4  
Ke y R oles a n d St u d y G o ver na nce  ........................................................................ 4 5  
1 0. 1. 5  
Cli nical M o nit ori n g  ............................................................................................... 4 5  
1 0 . 1. 6 
Q ualit y Ass ura nce a n d Q ualit y C o ntr ol  ................................................................ 4 5  
1 0. 1. 7  
Data Ha n dli n g a n d Rec or d Kee pi n g  ..................................................................... 4 6  
1 0. 1. 8  
Pr ot oc ol De viati o ns  ............................................................................................... 4 7  
1 0. 1. 9  
P u blicati o n a n d Data S hari n g P olic y  .................................................................... 4 7  
1 0. 1. 1 0  C o nflict of I nt erest P olic y  ..................................................................................... 4 7  
1 1  Refere nces  ............................................................................................................................ 4 8  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 0  of 5 9  
1 2  A p pe n dices  ........................................................................................................................... 4 9  
1 2. 1  
A p pe n di x 1: Sc he d ule of Pr oce d ures a n d Assess m e nts  ................................................ 5 0  
1 2. 2  
A p pe n di x 2: W o ma n of C hil d beari n g P ote ntial ( W O C B P)  .......................................... 5 1  
1 2. 3  
A p pe n di x 3: Slit La m p Bi o micr osc o p y  ........................................................................ 5 2  
1 2. 4  
A p pe n di x 4: N u meric Pai n Rati n g Scale ( N P R S) ......................................................... 5 4  
1 2. 5  
A p pe n di x 5: Best C orrecte d Vis ual Ac uit y ( B C V A)  .................................................... 5 5  
1 2. 6  
A p pe n di x 6: I ntra oc ul ar Press ure (I O P)  ....................................................................... 5 6  
1 2. 7  
A p pe n di x 7: Dilate d O p ht hal m osc o p y .......................................................................... 5 7  
1 2. 8  
A p pe n di x 8: C o m plia nce State me nt  ............................................................................. 5 8  
1 2. 9  
A p pe n di x 9: I n vesti gat or A gree me nt  ............................................................................ 5 9  
 
List of Ta bl es  
Ta ble 1  Pr o hi bite d Me dicati o ns a n d Pr oce d ures  ........................................................................ 2 6  
Ta ble 2  St u d y A d mi nistrati ve Str uct ure ..................................................................................... 4 5  
Ta ble 3  Slit La m p Tiss ue/ Str uct ure Assess me nts  ...................................................................... 5 2  
Ta ble 4  S U N W or ki n g Gr o u p Gra di n g Scale f or t h e A nteri or C ha m ber ................................... 5 3  
 
L ist of Fi g u res 
Fi g ure 1  Cli nical St u d y Dia gra m ................................................................................................. 1 7  
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 1  of 5 9  
A b b re vi ati o ns a n d D efi niti o n of Te r ms  
A C C  
a nteri or c h a m ber cell  
A C F  
a nteri or c h a m ber flare  
A E  
a d verse e ve nt  
A PI  
acti ve p har m ace utical i n gre die nt  
B C V A  
b est correcte d v is ual ac uit y 
C E L R  
cataract e xtracti o n a n d le ns re place me nt  
C F B  
c ha n ge fr o m baseli ne  
C F R  
C o de of Fe d eral Re g ul ati o ns  
e C R F 
electr o nic case re p ort f or m  
E T D R S  
Earl y Treat me nt Dia betic Reti n o pat h y St u d y  
F A S  
F ull A nal ysis Set  
F D A  
U nite d States F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d Cli nical Practice  
G L P  
G o o d La b orat or y Practice  
G M P  
G o o d Ma n ufact uri n g Practice  
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n  
I N D 
I n v esti gati o nal Ne w Dr u g 
I O P 
i ntra oc ular press ure 
I P 
i n vesti gati o nal pr o d u ct 
I R B 
I nstit uti o nal Re vie w B oar d  
J A K 
J a n us ki nase 
J A K-S T A T  
J a n us ki nase-si g nal tra ns d ucer a n d acti vat or of tra nscri pti o n 
L o g M A R  
L o garit h m of t he Mi ni m u m A n gle of Res ol uti o n  
Me d D R A  
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
N P R S  
N u meric Pai n Rati n g Scale  
N S AI D  
n o n -ster oi dal a nti-i nfla m mat or y dr u g 
P P  
Per Pr ot oc ol  
QI D  
q u ater i n die  (f o ur ti mes a da y) 
S A E  
seri o us a d verse e v e nt  
S A F  
Safet y A nal ysis Set  
S A P  
Statistical A nal ysis Pla n  
S U N  
Sta n dar dizati o n of U veitis N o me nclat ure  
T E A E  
treat me nt e mer ge nt a d verse e ve nt  
T Y K 2  
t yr osi ne ki nas e 2  
U S  
U nite d States  
V A  
vis ual ac uit y  
W H O Dr u g  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
W O C B P  
w o ma n of c hil d beari n g p ote ntial  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 2  of 5 9  
1  Intr o d ucti o n  
1. 1  
B ac k gr o u n d  
Intr a oc ular i nfla m mati o n is a n a ntici pate d se q uela of i ntra oc ul ar s ur ger y, s uc h as cataract 
e xtracti o n a n d le ns re pla ce me nt ( C E L R) s ur ger y , a n d is ma nifest e d pri nci pall y as c o nj u ncti val 
i njecti o n, c or neal e de m a, ciliar y fl us h, a n d a q ue o us cells a n d fl are. In ge neral, tra u ma t o t he 
i nter nal str uct ures of t h e e ye is acc o m p a nie d b y t he pr o d ucti o n of pr osta gla n di ns a n d ot her 
vas oacti ve m oieties,  t he releas e of pr o-i nfla m mat or y c yt o ki n es, a n i ncreas e i n bl o o d fl o w t o t he 
affecte d area, a n d e xtra vasati o n of pr otei n a n d cell ular bl o o d ele m e nts . U ntreate d i nfla m mati o n 
ma y l ea d t o c o m plicati o ns , s uc h as c yst oi d mac ular e de ma a n d c or neal scarri n g. T h us, ma na gi n g 
a n d treati n g p ost -o perati ve i nfla m mati o n is a n i m p orta nt g o al f oll o wi n g cataract s ur ger y ( Ki m et 
al., 2 0 1 9). 
C urre nt p ost -o perati ve m e dicati o n re gi me ns c o m m o nl y i ncl u de t o pical c ortic oster oi ds. Treat me nt 
wit h c or tic oster oi ds is e m pl o ye d t o re d u ce pai n a n d disc o mf ort, a n d t o facilitate rec o ver y of t he 
bl o o d -a q ue o us barri er. W he n a d mi nistere d at t he ti me of s ur ger y a n d d uri n g t he i m me diate p ost -
o perati ve peri o d, c ortic oster oi ds ca n re verse t he cli nical ma nifest ati o n s of i nfla m mati o n. I n t he 
U nite d States ( U S), t o pi cal c ortic oster oi ds are r o uti nel y prescri be d wit h u p t o f o ur ti mes dail y 
( QI D) d osi n g f or at least 2 wee ks f oll o wi n g cataract s ur ger y (Ki m et al., 2 0 1 9 ). 
T he J a n us ki nase (J A K) p at h wa y pla ys a ke y r ole i n i nfla m mat or y cell re g ul ati o n , cyt o ki ne 
pr o d ucti o n, a n d pr o -i nfl a m mat or y si g nal tra ns d ucti o n. D ysre g ulati o n of t he J A K pat h wa y is 
ass ociate d wit h t he pat h o ge n esis of vari o us i nfla m mat or y a n d a ut oi m m u ne dis or ders. T heref ore, 
J A K i nhi bit ors ha ve t he p ote ntial t o alle viate t he i nfla m mat or y pr ocess. T he J a n us ki nase-si g nal 
tra ns d ucer a n d acti vat or of tra nscri pti o n (J A K-S T A T) pat h wa y is k n o w n t o be i m p orta nt f or 
i nfla m mat or y cell re g ul ati o n, c yt o ki ne pr o d ucti o n, a n d pr o-i nfla m mat or y si gnal tra ns d ucti o n 
(We n et al., 2 0 2 1 ). 
V V N 4 6 1 is a hi g hl y acti ve J A K i n hi bit or wit h p ote nt i n hi biti o n of J A K 1 a n d t yr osi n e ki nase 2 
( T Y K 2), a n d m o d erate i n hi biti o n o n J A K 2. T h us, t his m olec ule is u n d er de vel o p me nt i n b ot h 
C hi na a n d t he  U S f or a nti -i nfla m mat or y acti vit y b y oral ( Q Y 2 0 1), t o pical der mal ( Q Y 2 1 1), a n d 
oc ular ( V V N 4 6 1) r o utes.  Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  ( Vi va Visi o n; S p o ns or) is 
c o n d ucti n g cli nical st u di es i n C hi na o n V V N 4 6 1 O p ht hal mic S ol uti o n f or t he treat me nt of n o n -
i nfecti o us a nteri or u veitis u n der a C hi nese I n vesti gati o nal Ne w Dr u g (I N D) a p plicati o n. The 
d osi n g re gi me ns i n t hese st u dies differ fr o m t h ose c urre ntl y i nte n de d f or t he o pe ni n g st u d y f or t he 
U S I N D  a p plicati o n , w hic h is t o pical oc ular treat me nt of p ost-o perati ve i nfla m mati o n a n d pai n 
f oll o wi n g i ntra o c ular s ur ger y. 
V V N 4 6 1 O p ht hal mic S ol uti o n is a preser ve d m ulti d ose pr o d uct, i nte n de d f or t o pical oc ular 
i nstillati o n. As a ne w c he mical e ntit y, the i nte n de d re g ulat or y r o ute is 5 0 5( b)( 1) . 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 3  of 5 9  
See t he I n vesti gat or’s Br oc h ure f or a d diti o nal i nf or mati o n.  
1. 2  
S t u d y R ati o n a le 
V V N 4 6 1 is a hi g hl y acti ve J A K i n hi bit or wit h str o n g i n hi biti o n o n J A K 1/ T Y K 2, a n d m o derate 
i n hi biti o n o n J A K 2. T he J A K-S T A T pat h wa y is a gr o u p of si g nali n g p at h wa ys c o m p ose d of 
rece pt ors, J A K pr otei ns, a n d si g nal tr a ns d ucers a n d tra nscri pti o n acti vat ors. Ma n y c yt o ki ne s 
d eli ver si g nals t hr o u g h t he J A K-S T A T pat h w a y. T heref ore, b ei n g cl osel y ass ociate d wit h t he 
h e mat ol o gic al s yste m a n d i m m u ne s yste m, t his si g nali n g pat h wa y pl a ys a n i m p orta nt r ole i n 
i m m u ne-me diate d i nfla m mat i o n (O’ S hea et al., 2 0 1 5 ; Star k & Dar nell, Jr., 2 0 1 2 ; Villari n o et al., 
2 0 1 5 ). 
O c ular i nfla m mati o n is k n o w n a n d e x pecte d t o occ ur after r o uti ne cataract s ur ger y. As a str o n g 
J A K i n hi bit or, it is t he orize d t hat V V N 4 6 1 ma y ha ve t hera p e utic be nefits f or  t he treat me nt of post -
o pera ti ve oc ul ar i nfla m m ati o n i n s u bjects u n der g oi n g r o uti ne cataract s ur ger y. 
1. 3  
R is k/ Be nefit Assess me nt 
T his secti o n pr o vi des hi g h -le vel i nf or mati o n re gar di n g k n o w n p ote ntial ris ks a n d be nefits. M ore 
detaile d i nf or mati o n ca n be f o u n d i n t he  I n vesti gat or’s Br oc h ure. 
1. 3. 1  
K n o w n P ote nti al Ris k s 
T here are k n o w n ris ks a n d c o m plicati o ns of r o uti n e cat aract s ur ger y, i ncl u di n g b ut n ot li mite d t o  
oc ular i nfla m mati o n, o c ular disc o mf ort, br uisi n g a n d s welli n g ar o u n d t h e s ur gical site, c ha n ges i n 
i ntra oc ular press ure (I O P), a n d op p ort u nistic i nfecti o n. I n rare  i nsta nces, lo n ger ter m 
c o m plicati o ns (e. g., p ost eri or ca ps ular o pacifi cati o n , cyst oi d mac ular e de ma ) ma y o cc ur. T h e se 
ris ks are n ot attri b uta ble t o t he i n vesti gati o nal pr o d uct (I P) b ut are i n here nt t o t he disease state 
bei n g  i n vesti gated . 
A  p hase 1 st u d y was c o n d ucte d i n  3 0 h ealt h y a d ult s u bjects t o e val uate t he safet y, t olera bilit y, a n d 
p har mac o ki netics of  V V N 4 6 1  (f or m ulati o n stre n gt hs 1. 0 % , 0. 5 %, a n d 0. 2 5 % ). The p h ase 1 st u d y 
re p orte d a relati vel y l o w i nci de nce of tr eat me nt e mer ge nt a d verse e v e nts ( T E A Es), wit h t he m ost 
c o m m o n a d verse e ve nts ( A Es) bei n g  i ntra oc ular press ure test a b n or mal ( 2/ 30; 6. 7 %), H er pes 
z oster ( 1/ 3 0; 3. 3 %) , a n d c or neal e pit heli u m d efect ( 1/ 3 0; 3. 3 %). I ntr a oc ular press ur e test 
a b n or malities were tra nsie nt, relate d t o I P , a n d res ol ve d wit h o ut i nter ve nti o n. T he i nci de nce of 
Her pes z oster was relate d t o I P  a n d res ol ve d wit h treat me nt.  T he i nci de n ce of c or neal e pit heli u m 
defect  w as n ot relat e d t o I P . 
1. 3. 2  
K n o w n P ote nti al Be nefit s 
T his is t he first st u d y of V V N 4 6 1 i n s u bjects u n d er g oi n g r o uti ne cataract s ur ger y. T h eref ore, t here 
are n o k n o w n o c ular h ealt h be nefits f or t his p o p ulati o n.   

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 4  of 5 9  
P re-cli nical st u dies i n D utc h ra b bits f o u n d t hat V V N 4 6 1 was c o m para ble t o a c ortic oster oi d 
c o m m o nl y use d i n cli nical practice, de x a m et has o ne o p ht hal mic s ol uti o n, 0. 1 %, at c o ntr olli n g  
oc ular i nfla m mati o n, re d uci n g t he e x u dati o n of a nteri or c ha m ber cells ( A C C s), a n d res ol vi n g 
i nfla m mat or y lesi o ns i n n o n-i nfecti o us u veitis. It is t he orize d t hat V V N 4 6 1 ma y ha v e t hera p e utic 
be nefits f or t he  tr eat me nt of p ost-o perati ve o c ular i nfla m mati o n after r o uti n e cataract s ur ger y.  
1. 3. 3  
Assess me nt of Be nefits a n d Ris ks  
It is t he j u d g me nt of Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d. t hat t here is a fa v ora ble be n efit-ris k 
rati o f or t he use of V V N 4 6 1  i n su bjects e x per i e nci n g p ost-o perati ve oc ular i nfla m mati o n aft er 
u n der g oi n g r o uti ne cataract s ur ger y. Pre -cli nical st u dies i n D utc h ra b bits f o u n d t hat V V N 4 6 1 
perf or me d c o m p ara bl y t o de x a met has o ne o p ht hal mic s ol uti o n, 0. 1 %, at c o ntr olli n g o c ular 
i nfla m mati o n, a n d V V N 4 6 1 may h a ve t he a d va nta ge of a v oi di n g si de effects, s uc h as cataract a n d 
i ncreas e d I O P, t hat are ass ociate d wit h l o n g-ter m use of de x a met has o n e o p ht hal mic s ol uti o n, 
0. 1 % . 
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 5  of 5 9  
2  St u d y  O bjecti ves a n d E n d p oi nts  
O bjecti ves  
E n d p oi nts  
Pri m ar y O bjecti ve:  
E val uate t he  o c ular efficac y of 2 differe nt 
d oses of V V N 4 6 1 O p ht hal mic S ol uti o n i n 
treati n g p ost-o perati ve oc ular i nfla m mati o n 
ass ociate d 
wit h cataract s ur ger y c o m pare d 
wit h t he oc ular efficac y of a matc hi n g Ve hi cle  
Sec o n d ar y O bjecti ve:  
E val uate t he safet y of V V N 4 6 1  
P ri m ar y E n d p oi nt:  
 Pr o p orti o n of s u bjects wit h A C C Gra de 0 
i n t he st u d y e ye at Visit 6 ( Da y 1 4) 
Sec o n d ar y E n d p oi nts:  
 Pr o p orti o n of s u bjects wit h A C C Gra de 0 
i n t he st u d y e ye at Visit 5 ( Da y 7) 
 Pr o p orti o n 
of 
s u bjects 
wit h 
a nteri or 
c ha m ber flare ( A C F) Gra de 0 i n t he st u d y 
e ye at Visit 6 ( Da y 1 4)  
 Pr o p orti o n of s u bjects wit h A C F Gra de 0 
i n t he st u d y e ye at Visit 5 ( Da y 7) 
 Pr o p orti o n of s u bjects re q uiri n g resc ue 
me dicati o n bef ore Visit 6 ( Da y 1 4)  
E x pl or at or y E n d p oi nts:  
 Mea n c ha n ge fr o m baseli ne ( C F B) i n A C C 
Gra de i n t he st u d y e ye at eac h visit 
 Mea n C F B i n A C F Gra d e i n t he st u d y e ye 
at eac h visit  
 Pr o p orti o n of s u bjects 
wit h n o p ost -
o perati ve oc ular pai n i n t he st u d y e ye at 
Visit 6 ( Da y 1 4)  
 Pr o p orti o n of s u bjects 
wit h n o p ost -
o perati ve oc ular pai n i n t he st u d y e ye at  
Visit 5 ( Da y 7)  
 
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 6  of 5 9  
3  St u d y  Desi g n  
3. 1  
O ver all Desi g n of t he St u d y  
T his is a  p hase 2, 
m ultice nter, d o u ble -mas k e d, ra n d o mize d, ve hicle -c o ntr olle d, parallel -
c o m paris o n st u d y c o n d ucte d at  sites in t he U S assessi n g t he safet y a n d oc ular efficac y of V V N 4 6 1 
f or treati n g p ost-o perati ve oc ular i nfla m mati o n  i n su bjects  w h o u n d er g o r o uti ne u nilateral C E L R 
s ur ger y via p h ac oe m ulsificati o n wit h o ut s ur gical c o m plicati o n. A p pr o xi matel y 9 0 c o m plete d 
s u bjects ( 3 0 per gr o u p) will be ra n d o mize d i n a 1: 1: 1 rati o. S u bjects wil l a d mi nister 1 e ye dr o p i n 
t he st u d y e ye f o ur ti mes a da y ( QI D) f or 1 4 da ys. The I P i n t he st u d y will b e: 
 V V N 4 6 1, 1. 0 %  
 V V N 4 6 1, 0. 5 %  
 Ve hicl e  
T here will be a t otal of 7 visits o ver a p pr o xi matel y 8 wee ks f or eac h s u bject. A  det aile d Sc he d ul e 
o f Pr oce d ures a n d Ass ess me nts i s pr o vi de d i n A p pe n di x 1 : Sc he d ule of Pr oce d ures a n d 
Assess me nt , a n d t he ge n eral fl o w of t h e st u d y is o utli ne d i n Fi g ure 1 .  
V isits will i ncl u de a scree ni n g visit, the d a y of cataract s ur ger y, a b aseli n e/ ra n d o mizati o n visit, 
a n d effic ac y a n d safet y e val uati o n visits after 3, 7, a n d 1 4 da ys of QI D d osi n g wit h I P i n t he st u d y 
e ye. T he st u d y will c o ncl u de wit h a safet y f oll o w -u p visit a p pr o xi matel y 1 wee k after t he e n d of 
t he pla n ne d d osi n g p eri o d. 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 7  of 5 9  
Fi g ure 1  
Cli nic al St u d y Di a gr a m  
 
A b bre viati o ns : I P =i n vesti gati o nal pr o d uct; QI D = q u ater i n die  (f o ur ti mes a da y) 
3. 2  
R ati o n ale f or t he St u d y  Desi g n  
P re-cli nical st u dies i n D utc h ra b bits f o u n d t hat V V N 4 6 1 was c o m para ble t o de x a met has o ne 
o p ht hal mic s ol uti o n, 0. 1 %, at c o ntr olli n g oc ular  i nfla m mati o n, re d uci n g t he e x u dati o n of A C C, 
a n d res ol vi n g i nfla m mat or y lesi o ns i n n o n -i nfecti o us u veitis. It is t he orize d t hat V V N 4 6 1 m a y 
ha ve t hera p e utic be nefits f or t he treat me nt of p ost -o perati ve oc ular i nfl a m mati o n after r o uti ne 
cataract s ur ger y. T he us e of Ve hicle as a c o ntr ol is sta n dar d practice i n o p ht hal m ol o g y  res earch.  
See t he I n vesti gat or’s Br oc h ure f or a d diti o nal i nf or mati o n.  
3. 3  
D ose J ustific ati o n  
T he I P f or m ulati o n stre n gt hs  (1. 0 % a n d 0. 5 % ) pr o p ose d f or t he st u d y were selecte d bas e d o n t heir 
pre vi o us use i n a p hase 1 st u d y i n healt h y a d ult h u ma n s u bjects a n d are furt her s u p p orte d b y 
e xte nsi ve n o n -cli nical a n d pre -cli nic al testi n g i n a ni mal m o dels.  
See t he I n vesti gat or’s Br oc h ure f or a d diti o nal i nf or mati o n.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 8  of 5 9  
3. 4  
E n d of St u d y  Defi niti o n  
A  s u bject is c o nsi dere d t o ha ve c o m plete d t he st u d y if t he s u bject has c o m plete d t he last visit or 
t he last sc he d ule d pr oce d ure s h o w n i n t he Sc he d ule of Pr oce d ures a n d Assess me nts ( A p pe n di x 1 : 
Sc he d ule of Pr oce d ures a n d Assess me nt ). The e n d of t he st u d y is defi ne d as c o m ple ti o n of t he last 
visit or pr oce d ure s h o w n i n t he sc he d ule i n t he st u d y gl o ball y.  
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 1 9  of 5 9  
4  St u d y  P o p ul ati o n  
T he st u d y p o p ulati o n will c o nsist of s u bjects w h o h a ve u n der g o ne r o uti ne u nilateral C E L R s ur ger y 
via p hac oe m ulsific ati o n wit h o ut s ur gical c o m plicati o n.  
4. 1  
I ncl usi o n Criteri a 
S u bjects 
w h o 
meet 
all i ncl usi o n 
criteria  at 
Visit 
1 ( Scree ni n g) 
a n d/ or 
Visit 
3 
(Bas eli ne/ Ra n d o mizati o n ) will be eli gi ble f or st u d y partici pati o n . 
1.  ≥2 1 years of a ge a n d i n g o o d ge n eral h ealt h at Visit 1 ( Scree ni n g)  
2.  Willi n g a n d a ble t o pr o vi de i nf or me d c o nse nt a n d pr o vi de rel e va nt pri v ac y a ut h orizati o n(s)  
3.  Willi n g a n d a ble t o c o m pl y wit h st u d y re q uire m e nts a n d visit sc he d ule  
4.  Clear oc ular m e dia ( ot her t ha n cataract) i n t he st u d y e ye  
5.  Pla n ni n g t o u n der g o r o uti ne u nilateral C E L R s ur ger y via p h ac oe m ulsificati o n e xtracti o n 
a n d i m pla ntati o n of a n i ntra oc ular l e ns. All o w e d  i n t he st u d y e ye at Visit 2 ( Da y of 
S ur ger y):  
a. Li m bal r ela xi n g i ncisi o ns (laser -assiste d a n d n o n -l aser) 
b.  I ntr aca meral i njecti o ns a n d i ntraca m eral me dicati o ns, e x cl u di n g t h ose i de ntifie d i n 
E x cl usi o n Criteri o n # 2  
6.  At Visit 1 ( Scree ni n g), has t he p ote ntial, i n t he o pi ni o n of t he I n v esti gat or , for p ost o perati ve 
best c orrect e d vis ual ac uit y ( B C V A ) ≤0 . 2 L o garit h m of t he Mi ni m u m A n gle of Res ol uti o n 
( L o g M A R) (i.e., 2 0/ 3 2 S nelle n or b etter) i n t he st u d y e ye as ass esse d usi n g Earl y Treat me nt 
Dia betic Reti n o pat h y St u d y ( E T D R S)  
7.  A t Visit 1 ( Scree ni n g), h as B C V A ≤1. 0 L o g M A R (i.e., 2 0/ 2 0 0 S nelle n) i n t he n o n -st u d y 
e ye d ue t o pat h ol o g y ot h er t ha n cataract as ass esse d usi n g E T D R S  
8.  A ble t o self -a d mi ni ster e ye dr o ps 
9.  At Visit 3 ( Baseli ne/ Ra n d o mizati o n; Da y 1), has A C C Gra de  ≥2 i n t he st u d y e ye  
4. 2  
E xcl usi o n Criteri a  
S u bjects w h o meet a n y of t he f oll o wi n g e x cl usi o n criteria will n ot be eli gi ble f or st u d y 
partici pati o n.  
O p ht h al mic  ( Eit her E ye) 
1.  A n y o c ular pai n at Visit 1 ( Scree ni n g)  
2.  Use d wit hi n 1 wee k bef ore Visit 2 ( Da y of S ur ger y), or be pla n ni n g t o use d uri n g t he st u d y, 
c ortic oster oi ds, oral or t o pical n o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds), or 
O mi dria ®  (i.e., p h e n yle p hri ne a n d ket or ol ac i njecti o n).  
N ote : L o w-d os e acet yls alic ylic aci d (i.e., ba b y as piri n or si milar) is all o we d  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 0  of 5 9  
3.  M o derate t o se v ere li d, c o nj u ncti val, or c or neal fi n di n gs at Visit 1 ( Scree ni n g)  
4.  C or neal a b n or malit y (e. g., str o mal, e pit helial, or e n d ot helial d ystr o p hies, i ncl u di n g 
e pit helial  base me nt me m bra ne d ystr o p h y)  
5.  Hist or y of c hr o nic/r ec urre nt i nfla m mat or y e ye dis ease (e. g., scleritis, a n y u veitis, her pes 
keratitis)  
6.  A n y si g ns of i ntra o c ular i nfla m mati o n (cell/flare) at Visit 1 ( Scree ni n g)  
7.  I O P ≥2 4 m m H g at Visit 1 ( Scree ni n g)  
O p ht h al mic ( S t u d y E ye) 
8.  Usi n g or u n willi n g t o f or g o c o ntact le ns use wit hi n defi ne d wi n d o ws bef ore Visit 2 ( Da y 
of S ur ger y) a n d f or t he d urati o n of t he st u d y  
a. P ol y m et h yl met hacr yl ate c o ntact l e nses ( 6 m o nt hs bef ore s ur ger y a n d t hr o u g h o ut 
st u d y) 
b.  Gas per mea ble ri gi d le ns es  ( 1 m o nt h bef ore s ur ger y a n d t hr o u g h o ut st u d y) 
c. E xte n de d wear or d ail y s oft le nses ( 7 da ys b ef ore s ur ger y a n d t hr o u g h o ut st u d y)  
9.  K n o w n pat h ol o g y t hat ma y affect vis ual ac uit y, partic ularl y reti nal c ha n ges t hat affect 
visi o n (e. g., 
mac ular de ge nerati o n, c yst o i d 
mac ular e d e ma, pr oliferati ve dia betic 
reti n o pat h y) 
1 0.  Ca ps ule or z o n ular a b n or malities wit h pre -o p erati ve cr ystalli ne l e ns tilt or dece ntrati o n 
(e. g., Marfa n’s s y n dr o me) or a b n or malities t hat ma y affect p ost-o perati ve ce ntrati o n or tilt 
of t he cr ystalli ne le ns (e. g., pse u d o e xf oliati o n s y n dr o me) 
1 1.  Hist or y of m o derate t o se vere oc ular tra u ma wit h t he p ossi bilit y of pre vi o us z o n ule 
de hisce nce  
1 2.  Oc ular or p eri oc ular s ur gic al i nter ve nti o ns wit hi n defi ne d wi n d o ws bef ore Visit 1 
( Scree ni n g) 
a. Micr oi n vasi ve gl a uc o ma s ur g er y, a n y i ncisi o nal oc ular s ur ger y, or i ntraca meral 
dr u g d e p ot t o l o wer I O P (a n y hist or y)  
b.  I ntr a oc ular s ur ger y ( 6 m o nt hs) 
c. Las er s ur ger y, li m bal rel a xi n g i ncisi o n pr oce d ure, e yeli d s ur ger y ( 3 m o nt hs)  
1 3.  P u pil a b n or malities (e. g., n o n -reacti ve, t o nic p u pils, a b n or mall y s h a pe d p u pils, p u pils t hat 
d o n ot dilate at least 3. 5 m m u n der mes o pic/sc ot o pic c o n diti o ns)  
1 4.  Kerat oc o n us or si g nifica nt irre g ular asti g matis m o n pre -o perati ve oc ul ar t o p o gra p h y  
1 5.  Ha ve a c o n diti o n, or be i n a sit uati o n, t hat ma y p ut t he s u bject at s i g nifica nt ris k of c o m ple x 
s ur ger y a n d s ur gical c o m plicati o ns t hat w o ul d lea d t o wit h dra wal fr o m t he st u d y 
O p ht h al mic ( N o n -st u d y E ye) 
1 6.  U n der we nt cataract s ur ger y  < 1 4 da ys b ef ore Visit 1 ( Scree ni n g) or, d uri n g t he st u d y, will 
re q uire cataract s ur ger y < 1 da y aft er Visit 2 ( Da y of S ur ger y)  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 1  of 5 9  
Ge ner al  
1 7.  Wit hi n 3 0 da ys b ef ore Visit 1 ( Scree ni n g), p artici p ate d i n a n i n vesti gati o nal dr u g or de vice 
st u d y, or ha v e use d a n i n vesti gati o nal dr u g or de vice 
1 8.  Aller g y or h y perse nsiti vit y t o t he I P or its e xci pie nts  
1 9.  Si g nifica nt s yste mic dise ase (e. g., u n c o ntr olle d dia betes; m yast he nia gra vis; he patic, re n al, 
car di o vas c ular, or e n d ocri ne dis or ders)  
2 0.  U nc o ntr olle d s yste mic disease, d efi ne d as, wit hi n 3 0 da ys bef ore Visit 1 ( Scree ni n g), a 
c ha n ge i n dise ase stat us or me dicati o ns t hat m a y p ut t he s u bject at i ncrease d ris k or 
c o nf o u n d i nter pretati o n of st u d y res ults  
2 1.  C ha n ges wit hi n 3 0 da ys bef ore Visit 1 ( Scree ni n g), or a ntici pate d c ha n ges d uri n g t he st u d y, 
t o t he d osa ge of s yste mic me dicati o n t hat c o ul d ha ve a s u bsta ntial effect o n I O P 
2 2.  K n o w n blee di n g te n de n cies  
2 3.  Ac ute or c hr o ni c disease or ill ness t hat w o ul d p ut t he s u bject at i ncreas e d ris k or c o nf o u n d 
i nter pretati o n of st u d y res ults (e. g., a ut oi m m u ne disease, c o n necti ve tiss ue disease, 
i m m u n o deficie nc y, s us p ecte d gla uc o ma, gla uc o mat o us c ha n ges i n t he f u n d us or vis ual 
fiel d, oc ular i nfla m mati o n, etc.) 
2 4.  Re q uires, is li kel y t o re q uire, or is u n willi n g t o disc o nti n ue t he use of pr o hi bite d 
me dicati o ns  
2 5.  Pre g n a nt, n ursi n g, or pla n ni n g a pre g na n c y d uri n g t he st u d y  
2 6.  U n willi n g or u na ble t o use a n acce p ta bl e met h o d of c o ntrace pti o n t hr o u g h o ut t he st u d y if 
a w o ma n of c hil d beari n g p ote ntial ( W O C B P ; A p pe n di x 2 : 
W o ma n of C hil d beari n g 
P ote ntial ( W O C B P) ) 
2 7.  U n willi n g or u na ble t o use a n acce pta bl e met h o d of c o ntrace pti o n t hr o u g h o ut t he st u d y if 
a male se x ual part ner of a W O C B P  
4. 3  
Scree n F ail ure s 
S cree n fail ures are defi n e d as s u bjects w h o c o ns e nt t o partici pate i n t he st u d y b ut w h o are n ot 
s u bse q ue ntl y ra n d o ml y assi g ne d t o I P a n d ent ere d i n t he st u d y. A  mi ni mal set of scree n fail ure 
i nf or mati o n is re q uir e d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure s u bjects, t o meet t he 
C o ns oli date d Sta n dar ds of Re p orti n g Trials p u blis hi n g re q uir e me nts , a n d t o res p o n d t o q ueries 
fr o m re g ulat or y a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, scree n fail ure details, 
eli gi bilit y criteria, a n d a n y seri o us a d verse e v e nt  ( S A E), or n o n-seri o us A Es.  
P r os pecti ve s u bjects wh o d o n ot meet t he criteria f or st u d y partici pati o n  (scree n fail ure) b eca us e 
of tra nsie nt c o n diti o ns t hat are e x pecte d t o c h a n ge, i ncl u di n g b ut n ot li mite d t o scree n fail ures f or 
hi g h I O P, m a y b e rescree ne d a t I n v esti gat or discreti o n ( ma xi m u m of 1 rescree n p er pr os pecti ve 
s u bject). Rescree n e d s u bjects s h o ul d be assi g ne d a ne w s u bj ect  i de ntificati o n n u m ber , an d t he 
ori gi nal s u bject i de ntificati o n n u m ber s h o ul d be rec or de d as a scree n fail ure. 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 2  of 5 9  
5  St u d y  Tre at me nt (s) or I nter ve nti o n(s) 
5. 1  
I n vesti g ati o n al Pr o d ucts 
T hree ( 3) I Ps will be a d mi nistere d d uri n g t he st u d y: 
 V V N 4 6 1, 1. 0 %  
 V V N 4 6 1, 0. 5 %  
 Ve hicle  
T he matc hi n g V e hicle will be i de ntical t o  t he acti ve d oses of I P, ex ce pt Ve hicle will n ot c o ntai n 
t he acti ve p h ar mace utical i n gre die nt ( A PI). All I P will be a d mi nistere d t o picall y t o t h e st u d y e ye 
as e ye dr o ps. 
5. 1. 1  
Descri pti o n  
B ot h f or m ulati o ns of V V N 4 6 1 a n d t he m atc hi n g Ve hicle are c ol orless t o li g ht yell o w sterile 
s ol uti o ns pac ka ge d i n 5 m L m ulti d ose l o w -de nsit y p ol yet h yle ne e ye dr o p b ottles. T he I P  will be 
pr o vi de d i n i d e ntical pri mar y pac ka gi n g . IP will be s u p plie d t o sites i n cart o ns. Eac h cart o n will 
c o ntai n 1 l o w -de nsit y p ol yet h yle n e e ye dr o p b ottl e. 
5. 1. 2  
D os a ge a n d A d mi nistr ati o n  
S u bjects will be ra n d o mize d t o 1 of 3 p ossi ble gr o u ps i n a 1: 1: 1 rati o. St u d y pers o n nel will pr o vi de 
trai ni n g t o s u bjects o n pr o per e ye dr o p a d mi nistrati o n, p r o per I P st ora ge w he n n ot i n use, a n d 
pr o per use of t he d osi n g diar y . 
A ll s u bjects, irres pecti ve of gr o u p, will a d mi nister 1 e ye dr o p i n t he st u d y e ye QI D f or a peri o d of 
1 4 da ys.  If t h e s u bject misses t heir e ye w hile a d mi nisteri n g a n e ye dr o p, a sec o n d e ye dr o p ma y 
be a d mi nistere d. If t he s u bject misses t heir e ye w hile a d mi nisteri n g a s ec o n d e ye dr o p, a t hir d e ye 
dr o p ma y n ot be a d mi nistere d. T h e misse d d ose s h o ul d be rec or de d i n t he d osi n g diar y.  
If a s u bject f or gets or misses a sc h e d ule d d ose of I P, t he s u bject s h o ul d a d mi nister  t he misse d d ose 
as s o o n as p ossi ble . Th e misse d d ose s h o ul d be rec or de d i n t h e d osi n g diar y. T he  QI D d osi n g 
sc he d ule s h o ul d t he n be res u me d. S u bjects w ill a d mi nister  t heir first d ose of I P a n d ma ke t heir 
first d osi n g diar y e ntr y i n t he c li nic u n der t he s u pervisi o n of st u d y p ers o n nel t o e ns ure pr o per 
d osi n g tec h ni q ue  a n d d osi n g diar y us e.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 3  of 5 9  
5. 2  
Pre p ar ati o n/ St or a ge/ H a n dli n g/ Acc o u nt a bilit y  
5. 2. 1  
Ac q uisiti o n a n d Acc o u nt a bilit y  
IP will be pr o vi de d t o eac h site. O nce t he I P has bee n deli vere d t o t he site, it will be st ore d i n a 
li mite d-access area o nl y accessi ble t o trai ne d st u d y pers o n nel . Use d a n d u n use d I P will be 
mai ntai ne d at t he site f or acc o u nta bilit y b y t he cli nical st u d y m o nit or.  
W he n a ut h orize d b y t h e S p o ns or , a n d after t he cli nical st u d y 
m o nit or has v erifie d dr u g 
acc o u nta bilit y is c o m plete a n d acc urate, use d a n d u n use d I P  eit her will be r et ur ne d t o t he S p o ns or 
or desi g nee , or will be dis p ose d/ destr o ye d b y t h e sites i n acc or da nce wit h t he re q uire me nts of 
a p plica ble l o cal a ut h orities a n d re g ul at or y b o dies t o e ns ure dis p osal of I P d oes n ot e x p ose h u ma n 
bei n gs t o ris ks fr o m t he dr u g.  
5. 2. 2  
Pr o d uct F or m ul ati o n, A p pe ar a nce, P ac k a gi n g, a n d L a beli n g  
IP will be  d eli vere d t o sites i n i de ntical pac ka gi n g a n d l a bele d i n acc or da n ce wit h fe d eral 
re g ulati o ns f or i n vesti gati o nal ne w dr u gs. La bels will i ncl u de ver bati m t he f oll o wi n g state m e nt: 
“ Ca uti o n: N e w Dr u g –  Li mite d b y Fe deral la w t o i n vesti gati o nal us e. ”  
T he f or m ulati o n i ncl u d es p ol yet h yle n e gl yc ol (a c os ol ve nt), h y dr o x y pr o p yl bet a -c ycl o de xtri n (a 
s ol u bilizer), citric aci d (a p H b uffer), s o di u m citrate (a p H b uffer), s o di u m c hl ori de (a t o nicit y 
a ge nt), a n d a preser vati v e, be nzal k o ni u m c hl ori de 0. 0 2 % ( w/ v). Water f or i njecti o n is use d as t he 
fi nal dil ue nt f or t his pr o d uct. T here are n o n o v el e x ci pie nts use d i n t he f or m ulati o n. T he pr o d uct 
is ma n ufact ur e d ase pticall y a n d is i nte n de d t o be use d as a sterile pr o d uct as Ve hi cle ( 0 . 0 % 
V V N 4 6 1), 0. 5 % V V N 4 6 1, a n d 1. 0 % V V N 4 6 1 . 
A d diti o nal details ma y als o be i ncl u de d o n t he la bel, pr o vi de d t hat t hese details d o n ot p ose a ris k 
t o st u d y mas ki n g. T his ma y i n cl u de b ut is n ot li mite d t o t he pr ot oc ol n u m ber, I P v ol u me per 
c o ntai ner, st ora ge re q uire me nts, ma n ufact ur er, a n d l ot n u m ber.  
5. 2. 3  
Pr o d uct St o r a ge a n d St a bilit y  
IP will be st ore d at a m bi e nt r o o m  te m perat ur e ( 1 5° C t o 2 5° C [ 5 9° F t o 7 7° F]) a n d pr otecte d fr o m 
li g ht i n a li mite d-access area accessi ble o nl y t o trai ne d st u d y pers o n nel.  O ne -d a y te m perat ure 
e x c ursi o ns d uri n g ha n dli n g, ware h o usi n g, a n d s hi p pi n g o perati o ns are per mitte d u p t o 4 0 ° C 
(1 0 4° F ), b ase d o n sta bilit y dat a.  
O pe ne d a n d u n o p e ne d  b ottles of I P will be m ai ntai ne d at t h e site f or acc o u nta bilit y b y t he cli nical 
st u d y m o nit or. 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 4  of 5 9  
5. 3  
Me as ures t o Mi ni miz e Bi as: R a n d o miz ati o n a n d M as ki n g  
E li gi ble s u bjects will be ra n d o mize d in a 1: 1: 1 rati o i n t he electr o nic data ca pt ure syst e m . The I P 
will be dis pe nse d to s u bjects b y trai ne d st u d y pers o n nel  o nl y . 
T he ra n d o mizati o n sc he d ule will be c o m p uter -ge n erate d i n t he electr o nic data ca pt ur e s yste m , a n d 
all I P will be mas ke d t o t he S p o ns or, st u d y pers o n nel,  a n d st u d y s u bjects t hr o u g h o ut t he st u d y u ntil 
after t h e fi nal d ata base has bee n l oc ke d. A p pr o priate preca uti o ns m ust be ta ke n t o pre ve nt 
u na ut h orize d access t o t he ra n d o mizati o n sc he me. U nless t he s u bject’s safet y re q uir es ot her wise , 
a n d if ti me per mits, t he decisi o n t o u n mas k a treat me nt assi g n me nt is t o be ma de j oi ntl y b y t h e 
I n v esti gat or a n d t he M e dical M o nit or  after c o ns ultati o n wit h t he S p o ns or.  
If u n mas ki n g is re q uir e d d uri n g t he st u d y, t he i nte grit y of t h e st u d y assess m e nts a n d c ollect e d data 
will b e mai ntai ne d b y li miti n g access t o t he u n mas ke d data.  
5. 4  
D osi n g A d here nce a n d D osi n g Di ar y  
5. 4. 1  
D osi n g A d here nce  
S t u d y pers o n n el will pr o vi de trai ni n g t o s u bjects o n pr o per e ye dr o p a d mi nistrati o n , pr o per I P 
st ora ge w h e n n ot i n use, a n d pr o per use of t he d osi n g diar y. S u bjects will als o recei ve writte n 
i nstr ucti o ns. S u bjects will recei ve a n e w s u p pl y of I P, as a p plica ble, as i n dicate d i n A p pe n di x 1 : 
Sc he d ule of Pr oce d ures a n d Assess me nt . St u d y p erso n nel will re vie w s u bject d osi n g a d h ere n ce, 
as rec or de d i n t he d osi n g diar y, at eac h pl a n ne d visit a n d will pr o vi de re mi n ders a n d i nstr ucti o n 
a b o ut t he QI D d osi n g sc h e d ule a n d d osi n g a d here n ce, as nee de d.  
5. 4. 2  
D osi n g Di ar y  
S u bjects will be as ke d t o rec or d t hei r dail y use of I P i n a d osi n g diar y t hat will be c ollecte d a n d 
re vie we d wit h t he m d uri n g eac h pla n ne d visit. S u bjects will recei ve ver bal a n d writte n i nstr ucti o n 
o n t he pr o per us e of t he d osi n g diar y at Visit 3 ( Baseli ne/ Ra n d o mizati o n ), as well as v er bal an d 
writte n i nstr ucti o n o n pr o per e ye dr o p a d mi nistrati o n  a n d pr o per I P st ora ge w he n n ot i n use f or 
d osi n g.  
E m pt y fiel d e ntries i n t he d osi n g diar y will be c o u nte d as misse d d oses, o nce verifie d wit h t he 
s u bject, f or t he p ur p ose of meas uri n g d osi n g a d here nce. St u d y pers o n nel will re vie w s u bj ect 
d osi n g a d here nce, as rec or de d i n t he d osi n g diar y, at eac h pla n ne d visit a n d will pr o vi de re mi n ders 
a n d i nstr ucti o n a b o ut pr o per use of t he d osi n g diar y, as n ee de d.  
5. 5  
Pri o r a n d C o nc o mit a nt T her a p y  
F or t his pr ot oc ol, a prescri pti o n me dicati o n is defi ne d as a m e dicati o n t hat ca n be prescri be d o nl y 
b y a pr o perl y a ut h orize d/lice nse d cli nicia n . M e di cati o ns t o be re p orte d i n t he  electr o nic cas e re p ort 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 5  of 5 9  
f or m (eC R F ) are c o nc o mita nt 
prescri pti o n 
me dicati o ns, 
o ver-t he-c o u nter 
me dicati o ns , 
su p ple me nts , a n d me dicati o ns pr o vi de d at Visit 2 ( Da y of S ur ger y) as part of site’s sta n dar d 
practice d uri n g r o uti ne cataract s ur ger y . (N ote:  C ortic oster oi ds, oral or  t o pical N S AI Ds [e x cl u di n g 
lo w -d ose acet ylsalic ylic aci d ], a n d Omi dri a ®  [i.e., p he n yle p hri ne a n d k et or olac i njecti o n] are 
pr o hi bite d .) 
A ll me dicati o ns t hat t he s u bject has ta ke n wit hi n 3 0 da ys bef ore Visit 1 ( Scree ni n g) a n d t hr o u g h 
Visit 7 ( Da y 2 1; E n d of St u d y) or e xit fr o m t he st u d y will be rec or de d i n t he e C R F a n d t he s u bject’s 
s o urce d o c u me nts. S u bjects will be as ke d f or details a b o ut a n y c h a n ges i n d o c u me nte d me dicati o ns 
at all visits. T h e ge neric n a me of t he dr u g, d ose, r o ute of a d mi nistrati o n, d urati o n of treat me nt 
(i ncl u di n g start a n d st o p dates), fre q ue nc y, i n dicatio n, a n d w het her or n ot t he me dicati o n was ta ke n 
d ue t o a n A E or as resc ue will be rec or de d f or eac h me dicati o n. Pri or a n d c o n c o mita nt me dicati o ns 
will be c o de d usi n g t h e W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y ( W H O Dr u g).  
5. 5. 1  
Pr o hi bite d Me dic ati o ns a n d Pr oce d ures  
M e dicati o ns t hat are n ot e x plicitl y pr o hi bite d b y t he pr ot oc ol ma y b e use d, as n ee de d, t hr o u g h o ut 
t he st u d y a n d rec or de d as c o nc o mita nt me di cati o ns. All me dicati o ns t a ke n b y a s u bject d uri n g t he 
st u d y, w h et her all o we d or pr o hi bite d, s h o ul d b e rec or de d as c o nc o mita nt m e dicati o ns . Ta ble 1  lists 
t he pr o hi bite d me dicati o ns a n d pr oce d ures f or t he p ur p oses of t he st u d y, as well as t h e mi ni m u m 
ti mefra mes f or dis c o nti n uati o n nee de d f or st u d y eli gi bility .  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 6  of 5 9  
T a ble 1  
Pr o hi bite d Me dic ati o ns a n d Pr oce d ures  
M e dic ati o ns a n d Pr o ce d ures N ot Per mitte d  
Ti mefr a me  
O p ht h al mic ( St u d y E ye) 
Micr oi n vasi ve gla uc o ma s ur ger y, a n y i ncisi o nal oc ular 
s ur ger y, or i ntraca meral dr u g de p ot t o l o wer I O P  
A n y hist or y a n d t hr o u g h o ut st u d y  
I ntra o c ular s ur ger y 
6 
m o nt hs 
bef ore s ur ger y a n d t hr o u g h o ut st u d y 
(e xcl u di n g pla n ne d cataract s ur ger y) 
Laser s ur ger y, li m bal rela xi n g i ncisi o n pr oce d ure, e yeli d 
s ur ger y 
N ote: Li m bal rela xi n g i ncisi o ns (laser -assiste d a n d n o n -
laser) are all o we d i n t he st u d y e ye at Visit 2 ( Da y of 
S ur ger y)  
3 m o nt hs bef ore s ur ger y a n d t hr o u g h o ut st u d y  
C o ntact le nses  
T hr o u g h o ut st u d y a n d wit hi n defi ne d wi n d o ws bef ore 
Visit 2 ( Da y of S ur ger y)  
a. 
P ol y met h yl met hacr ylate c o nt act le nses  
b.  Gas p er mea ble ri gi d le nses  
c. 
E xte n de d wear or dail y s oft le nses  
a. 
6 m o nt hs bef ore s ur ger y  
b.  1 m o nt h bef ore s ur ger y  
c. 
7 da ys bef ore s ur ger y  
O p ht h al mic ( N o n-st u d y E ye) 
Cataract s ur ger y  
1 4 da ys bef ore Visit 1 ( Scree ni n g) or will re q uire 
cataract s ur ger y < 1 da y after Visit 2 ( Da y of S ur ger y)  
Ge ner al  
Ot her i n vesti gati o nal dr u g or de vice  
3 0 da ys bef ore Visit 1 ( Scree ni n g) a n d t hr o u g h o ut st u d y  
C ha n ges t o s yste mic 
me dic ati o n t hat c o ul d ha ve a 
s u bsta ntial effect o n I O P 
3 0 da ys bef ore Visit 1 ( Scree ni n g) a n d t hr o u g h o ut st u d y  
C ortic oster oi ds, oral or t o pical N S AI Ds, or O mi dria ®  
(i.e., p he n yle p hri ne a n d ket or olac i nj ecti o n) 
N ote : Lo w -d ose acet ylsalic yli c aci d (i.e., ba b y as piri n 
or si milar) is all o we d  
1 wee k bef ore Visit 2 ( Da y of S ur ger y)  a n d t hr o u g h o ut 
st u d y 
A b bre viati o ns: I O P=i ntra o c ul ar press ure; N S AI D = n o nster oi dal a nti -i nfla m mat or y dr u g 
5. 5. 2  
Resc ue Me dic ati o n  
S u bjects are eli gi ble t o be resc ue d at a n y ti me at t he I n vesti gat or’s dis creti o n a n d place d o n 
a p pr o priate treat me nt or t hera p y. Alt h o u g h t h e use of resc ue me dicati o n is all o wa ble at a n y ti me , 
a d va nce c o ns ultati o n wit h t he Me dical M o nit or is preferre d , if possi ble . If a dela y i n resc u e w o ul d 
place t he s u bject at u n necessar y ris k, t he I n vesti gat or s h o ul d pr ocee d wit h resc ue i m me diatel y .  
T he date  of r esc u e me di cati o n a d mi nistrati o n, as well as t he na me of t he resc ue  me dicati o n a n d 
d osa ge re gi me n, m ust be rec o r de d as c o nc o mita nt me dicati o ns i n t he e C R F, wit h a n ote i n dicati n g 
t hat t he me dicati o n was use d f or resc u e. S u bjects w h o re q uire resc ue will be c o u nte d as treat me nt 
fail ures a n d u n d er g o f oll o w-u p safet y assess me nts a n d pr oce d ures. E ver y atte m pt s h o ul d be ma de 
t o ha ve s u bjects c o nti n ue i n t he st u d y f or safet y e val uati o ns, e ve n if s u bjects disc o nti n ue I P. T he 
nee d f or resc u e me dicati o n itself will n ot be c o nsi dere d a n A E.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 7  of 5 9  
6  St u d y Disc o nti n u ati o n /S u bject  Wit h dr a w al  
6. 1  
Disc o nti n u ati o n of I n vesti g ati o n al Pr o d uct 
A  s u bject ma y b e disc o nti n ue d fr o m I P at a n y ti m e if t he s u bject, t he I n vesti gat or, or t he S p o ns or 
feels t hat it is n ot i n t he s u bject’s best i nterest t o c o nti n ue. S u bjects ma y h a ve I P wit h dra w n b y t he 
I n v esti gat or d ue t o a n A E or d ue t o t he nee d f or resc ue. S u bjects w h o ha v e I P wit h dr a w n d ue t o 
a n A E s h o ul d be f oll o we d f or at least 1 w ee k f or safet y m o nit ori n g, or u ntil t he A E has res ol v e d.  
6. 2  
S u bject  Disc o nti n u ati o n /Wit h dr a w al fr o m t he St u d y  
S u bjects  are free t o wit h dra w fr o m p artici pati o n i n t he st u d y at a n y  ti me u p o n re q uest. A n 
I n v esti gat or ma y disc o nti n ue or wit h dra w a s u bject fr o m t he st u d y f or a n y reas o n, i ncl u di n g b ut 
n ot li mite d t o t he f oll o wi n g:  
 A d verse e ve nt  
 Fail ure t o meet ra n d o mizati o n criteria  
 L ost t o f oll o w -u p  
 I n v esti gat or decisi o n  
 Pre g n a nc y  
 Pr ot oc ol de viati o n  
 Wit h dra wal of c o nse nt   
T he r eas o n f or s u bject disc o nti n uati o n or wit h dra wal fr o m t he st u d y will be rec or de d  i n t he e C R F. 
S u bject s w h o si g n t he i nf or me d c o nse nt f or m a n d are r a n d o mize d b ut  d o n ot recei ve I P ma y b e 
re place d. S u bjects w h o  si g n t h e i nf or me d c o ns e nt f or m, are ra n d o mize d, recei ve at least 1 d ose of 
I P, an d s u bse q u e ntl y wit h dra w or are wit h dra w n /disc o nti n ue d fr o m t he st u d y  m a y n ot b e r e place d.  
6. 3  
L ost t o F oll o w -U p  
A  s u bject will be c o nsi d ere d l ost t o f oll o w -u p if t hey fail t o ret ur n f or a s c he d ule d v isit a n d are 
u na ble t o be c o nta cte d b y st u d y pers o n nel. 
T he f oll o wi n g acti o ns m ust be ta ke n if a s u bject fails t o ret ur n t o a site f or a re q uir e d visit: 
 T he site will atte m pt t o c o ntact t he s u bject a n d resc he d ule t he misse d visit . The site will  
c o u nsel t he s u bject o n t he i m p orta nce of mai ntai ni n g t he assi g n e d visit sc he d ule a n d 
ascert ai n if t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he st u d y . 
 B ef ore a s u bject is dee m e d l ost t o f oll o w-u p, t he I n vesti gat or or desi g n ee will ma ke e ver y 
eff ort t o re gai n c o ntact wit h t he s u bject ( w h ere p ossi ble, 3 tele p h o ne calls a n d, if necessar y, 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 8  of 5 9  
a certifie d letter t o t he s u bject’s last k n o w n m aili n g a d dress or l ocal e q ui vale nt met h o ds). 
T hese c o nta ct atte m pts s h o ul d be d oc u me nte d i n t he s u bject’s me dical rec or d or st u d y fil e. 
 S h o ul d t he s u bject c o nti n ue t o be u nreac ha ble, t he s u bject will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y wit h a pri mar y reas o n of l ost t o f oll o w -u p . 
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 2 9  of 5 9  
7  St u d y  Pr oce d ure s 
W ritte n i nf or me d c o nse nt a n d rele v a nt pri vac y a ut h orizati o n(s) will be o btai ne d fr o m all s u bjects 
bef ore  a n y pr oce d ures relate d t o t he st u d y are perf or me d. T he Sc he d ul e of Pr oce d ures a n d 
Assess me nts  (A p p e n di x 1 : Sc he d ule of Pr oce d ures a n d Assess me nt) lists the pr oce d ures t hat 
s h o ul d occ ur at e ac h st u d y visit.  
7. 1  
V isit Descri pti o ns 
P r oce d ures s h o ul d be perf or me d i n t he or der liste d; pr oce d ures f oll o we d b y a n “ *” ma y occ ur at 
ot her ti mes d uri n g t he visit, if nee de d, t o  acc o m m o date site o perati o ns a n d/ or s u bject b o dil y 
f u ncti o ns, pr o vi de d t he pr oce d ure is c o m plete d bef ore i n-cli nic a d mi nistrati o n of I P. 
7. 1. 1  
Visit 1 ( Scree ni n g ; D a y -3 0 t o D a y -1 )  
T he f oll o wi n g pr oce d ures will be perf or me d at Visit 1 ( Scree ni n g; Da y -3 0 t o Da y -1 ): 
 E x plai n t he p ur p ose a n d c o n d uct of t he st u d y t o t h e s u bject, a ns wer su bject q uesti o ns, a n d 
o btai n writte n i nf or me d c o nse nt a n d  pri vac y a ut h orizati o n(s)  
 O btai n i nf or mati o n , i ncl u di n g: de m o gra p hics, c o nc o mita nt me dicati o ns, a n d oc ular a n d 
s yste mic me dical a n d me dicati o n hist or y a n d s ur gical hist or y  
 Heart rate a n d bl o o d pr ess ure  
 S u bject a d mi nistrati o n of test e ye dr op  
 Pai n sc ore trai ni n g  
 B C V A  
 Slit la m p bi o micr osc o p y  
 I O P 
 Dilate d o p ht hal m osc o p y  
 Uri ne pre g n a nc y test ( o nl y f or W O C B P) *  
 A b bre viate d p h ysic al e x a mi nati o n *  
 Deter mi ne st u d y eli gi bilit y base d o n I ncl usi o n/ E x cl usi o n criteria  
7. 1. 2  
Visit 2 ( D a y of S ur ger y; D a y 0)  
A t Visit 2 ( Da y of S ur ger y; 
D a y 0) , s u bjects 
will u n der g o r o uti ne C E L R s ur ger y via 
p hac oe m ulsificati o n e xtracti o n a n d i m pla ntati o n of a n i ntra oc ular le ns. I n vesti gat ors s h o ul d use 
t heir sta n dar d pr o ce d ure f or r o uti ne cataract s ur gery.  
Li m bal rela xi n g i ncisi o ns (laser -assiste d a n d n o n -laser) a n d i ntraca meral i njecti o ns a n d 
me dicati o ns are all o we d d uri n g t he s ur ger y. ( N ote:  C ortic oster oi ds , oral or  t o pical N SAI Ds  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 0  of 5 9  
[e x cl u di n g l o w -d ose acet ylsalic ylic aci d ], a n d O mi dria®  [i.e., p he n yl e p hri ne a n d ket or olac 
i njecti o n] are pr o hi bite d.) 
A ll me dicati o ns gi ve n t o s u bjects as part of t he cataract s ur ger y pr oce d ure, i ncl u di n g b ut n ot 
li mite d t o se dati ves, l ocal a nest hetics, a n d to pical a nti bi otics, s h o ul d be rec or de d i n t he e C R F as 
c o nc o mita nt me dicati o ns . 
A fter t he cataract s ur ger y, s u bjects s h o ul d n ot be pr o vi de d wit h a n y prescri pti o n or o ver-t he-
c o u nter pai n me dicati o n , or me dicati o n s i nte n de d t o mi ni mize oc ular i nfla m mati o n. S u bjects will 
be assesse d f or safet y a n d ra n d o mize d at Visit 3 ( Baseli ne/ Ra n d o mizati o n; Da y 1) . 
T he f oll o wi n g pr oce d ures will be perf or me d at Visit 2 ( Da y of S ur ger y):  
 A E m o nit ori n g  
 C o nc o mita nt me dicati o n  u p date  
 Uri ne pre g n a nc y test ( o nl y f or W O C B P) * 
 Cataract s ur ger y  
7. 1. 3  
Visit 3 ( B aseli ne/ R a n d o miz ati o n; D a y 1)  
T he f oll o wi n g pr oce d ures will be perf or me d  at Visit 3 ( Baseli ne/ Ra n d o mizati o n; Da y 1):  
 A E m o nit ori n g  
 C o nc o mita nt me dicati o n  u p date  
 Pai n sc ore trai ni n g  
 N u meric Pai n Rati n g Sca le (N P R S ) 
 B C V A  
 Slit la m p bi o micr osc o p y  
 I O P 
o  N ote : T he I O P pr oce d ure re q uires t he a d mi nistrati o n of pr o paracai n e 0. 5 % t o t he 
e ye b ef ore testi n g ; t here s h o ul d al wa ys b e ≥3 0 mi n utes bet wee n t he a d mi nistrati o n  
of t o pical a nest hetic a n d I P.  
 Deter mi ne st u d y eli gi bilit y base d o n I ncl usi o n/ E x cl usi o n criteria  
 Ra n d o mizati o n  
 Dis pe nse I P  
 Pr o vi de i nstr ucti o ns f or I P use, d osi n g a d here n ce, a n d d osi n g diar y e ntries  
 S u per vise d first d ose of I P  
 Sc he d ule  or c o nfir m n e xt visit a n d re mi n d s u bject t o ret ur n wit h d osi n g diar y  
7. 1. 4  
Visit 4 ( D a y 3 ± 1)  
T he f oll o wi n g pr oce d ures will be perf or me d at Visit 4 ( Da y 3 ± 1):  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 1  of 5 9  
 A E m o nit ori n g  
 C o nc o mita nt me dicati o n  u p date  
 N P R S  
 B C V A  
 Slit la m p bi o micr osc o p y  
 I O P 
 Re vie w d osi n g a d here nce a n d dair y e ntries  
 Sc he d ule or c o nfir m ne xt visit a n d re mi n d s u bject t o ret ur n wit h I P a n d d osi n g diar y 
7. 1. 5  
Visit 5 ( D a y 7 ± 1)  
T he f oll o wi n g pr oce d ures will be perf or me d at Visit 5 ( Da y 7 ± 1):  
 A E m o nit ori n g  
 C o nc o mita nt me dicati o n  u p date  
 N P R S  
 B C V A  
 Slit la m p bi o micr osc o p y  
 I O P 
 C ollect u n use d I P  
 Re vie w d osi n g a d here nce a n d dair y e ntries  
 Dis pe nse I P  
 Sc he d ule or c o nfir m ne xt visit a n d re mi n d s u bject t o ret ur n wit h I P a n d d osi n g diar y 
7. 1. 6  
Visit 6 ( E n d of Tre at me nt ; D a y 1 4 ± 2)  
T he f oll o wi n g pr oce d ures will be perf or me d at Visit 6 ( E n d of Treat me nt; Da y 1 4 ± 2) : 
 A E m o nit ori n g  
 C o nc o mita nt me dicati o n  u p date  
 N P R S  
 B C V A  
 Slit la m p bi o micr osc o p y  
 I O P 
 C ollect u n use d I P  
 Re vie w d osi n g a d here nce a n d dair y e ntries  
 Uri ne pre g n a nc y test ( o nl y f or W O C B P) *  
 Sc he d ule or c o nfir m ne xt visit  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 2  of 5 9  
7. 1. 7  
Visit 7 ( E n d of St u d y; E arl y Ter mi n ati o n; D a y 2 1 ± 2)  
T he f oll o wi n g pr oce d ures will be perf or me d at Visit 7 ( E n d of St u d y; E arl y Ter mi nati o n; Da y 2 1 
± 2):  
 A E m o nit ori n g  
 C o nc o mita nt me dicati o n  u p date  
 B C V A  
 Slit la m p bi o micr osc o p y  
 I O P 
 Dilate d o p ht hal m osc o p y  
 Uri ne pre g n a nc y test ( o nl y f or W O C B P) *  
 Release s u bject  fr o m st u d y 
7. 1. 8  
U nsc he d ule d Visits  
S afet y pr oce d ures a n d efficac y assess me nts c o n d ucte d at u ns c he d ule d visit s are at t he discreti o n 
of t he I n vesti gat or. I nf or mati o n will be c ollecte d d uri n g u nsc h e d ule d visits a b o ut c ha n ges t o 
c o nc o mita nt me dicati o ns a n d a n y A E s e x perie n ce d si nce t he last visit. 
If a s u bject re p orts t heir s u p pl y of I P t o be l ost, destr o ye d, or u n usa ble d ue t o u nacce pta ble 
te m perat ur e e x c ursi o ns, a ne w s u p pl y of I P ma y b e dis pe nse d t o t he s u bject. 
7. 1. 9  
E arl y Ter mi n ati o n  
In t he e ve nt t hat a s u bject wit h dra ws or is ter mi nate d fr o m t he st u d y  b ef ore t he e n d of t he st u d y, 
ever y atte m pt will be ma de t o ens ure t hat t he s u bject ret ur ns t o t he site as s o o n as p ossi ble a n d 
c o m pletes t he Visit 7 ( E n d of St u d y; Earl y T er mi nati o n) assess me nts bef ore bei n g disc har ge d fr o m 
t he st u d y. A n y u n use d I P s h o ul d be c ollecte d d uri n g a n earl y ter mi nati o n visit.  
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 3  of 5 9  
8  St u d y Assess me nt s 
T he Sc he d ule of Pr oce d ures a n d Assess me nts ( A p pe n di x 1 : Sc he d ule of Pr oce d ures a n d 
Assess me nt ) pr o vi des a list of st u d y assess me nts a n d e v al uati o ns t o be perf or me d a n d t he ti mi n g 
of eac h . 
8. 1  
Effic ac y E v al u ati o ns  
E fficac y ass ess me nts will be c o n d u cte d at t he ti me p oi nts i n dicate d o n t he Sche d ule of Pr oce d ures 
a n d Assess me nts ( A p pe n di x 1 : Sc he d ule of Pr oce d ures a n d Ass ess me nt) a n d as detaile d i n t he 
c orres p o n di n g a p pe n dic es. T he effic ac y assess me nts selecte d f or t he st u d y are c o m m o n t o ols 
wit hi n t he fiel d of o p ht hal m ol o g y a n d are ge nerall y rec o g nize d as relia ble, acc urate, a n d rele va nt  
i n assessi n g t he healt h a n d f u ncti o n of h u ma n e yes. Efficac y assess me nts i n t he st u d y i ncl u de: 
 S lit la m p bi o micr osc o p y (A p pe n di x 3 : Slit La m p Bi o micr osc o p)  
o  O c ular i nfla m mati o n ( Sta n dar dizati o n of U veitis N o me nclat ure [ S U N] Scale)  
 N u meric Pai n Rati n g Scale  (A p pe n di x 4 : N u meric Pai n Rati n g Scale ( N P R S)) 
8. 2  
S afet y E v al u ati o ns  
S afet y ass ess me nts will be perf or me d at t he ti me p oi nts i n dicate d o n t he S c he d ule of Pr oce d ures 
a n d Assess me nts ( A p pe n di x 1 : Sc he d ule of Pr oce d ures a n d Ass ess me nt) a n d as detaile d i n t he 
c orres p o n di n g a p pe n di ces. T he s afet y assess me nts selecte d f or t he st u d y are all c o m m o n t o ols 
wit hi n t he fiel d of o p ht hal m ol o g y a n d are ge nerall y rec o g nize d as relia ble, acc urate, a n d rele va nt 
i n assessi n g t he h ealt h a n d f u ncti o n of h u ma n e yes. Safet y assess me nts i n t he st u d y i ncl u de: 
 A E m o nit ori n g ( oc ul ar a n d n o n -oc ular ) 
 P re g n a nc y test ( uri ne; o nl y f or W O C B P as defi ne d i n A p pe n di x 2 : W o ma n of C hil d beari n g 
P ote ntial ( W O C B P) ) 
 Best correcte d v is ual ac uit y (A p pe n di x 5 : Best C orrect e d Vis ual Ac uit y ( B C V A) 
 Slit la m p bi o micr osc o p y ( A p pe n di x 3 : Slit La m p Bi o micr osc o p) 
 I ntr a oc ular press ure (A p pe n di x 6 : I ntr a oc ular Press ure (I O P)) 
 D ilate d o p ht hal m osc o p y (A p pe n di x 7 : Dilate d O p ht hal m osc o p) 
8. 2. 1  
A d verse E ve nt s an d Seri o us A d verse E ve nt s 
A Es  will be m o nit ore d t hr o u g h o ut t he st u d y. S u bject s will be e nc o ura ge d t o re p ort a n y a d v erse 
fi n di n gs d uri n g t he st u d y, w het her or n ot t he y are relate d t o I P. T hese ca n be c ollecte d eit her i n a n 
u ns olicite d fas hi o n wit h o ut a n y pr o m pti n g or i n res p o nse t o a ge neral q uesti o n s uc h as: “ Ha v e y o u 
n otice d a n yt hi n g differe nt si nce y o u starte d t he st u d y; be ga n t he I P, etc .? ” 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 4  of 5 9  
A ll AEs will be ca pt ure d o n t he a p pr o priate  s o urce d oc u me nts a n d rec or de d i n t he e C R F. 
Inf or mati o n t o be c ollecte d at mi ni m u m i ncl u des e ve nt des cri pti o n, o nset, assess me nt of s e verit y, 
relati o ns hi p t o I P, a n d outc o me . 
T he I n vesti gat or will rec or d all A Es wit h s tart dates occ urri n g a n y ti me aft er i nf or me d c o nse nt is 
o btai ne d u ntil 7 (f or n o nseri o us A Es) or 3 0 da ys (f or  S A Es) a fter t he last da y of st u d y partici pati o n. 
At eac h visit, t he I n vesti gat or will i n q uire a b o ut t he occ urre n ce of A E s/ S A Es si nce t he last visit. 
S A Es will be f oll o we d f or o utc o me i nf or mati o n u ntil res ol uti o n or sta bilizati o n . 
A n y me dical c o n diti o n t hat is prese nt at t he ti me t hat t he s u bject is scree ne d will be c o nsi dere d as 
baseli ne a n d n ot re p ort e d as a n A E. H o we v er, if t he s u bject’s c o n diti o n deteri orat es at a n y ti me 
d uri n g t he st u d y, it will be rec or de d as a n A E . 
8. 2. 1. 1  Defi niti o n s 
A n A E i s a n y u nt o war d me dical occ urre nce i n a s u bject te m p orall y ass ociate d wit h t he use of I P, 
w het her or n ot c o nsi dere d relate d t o t he I P. An A E ca n t heref ore b e a n y u n fa 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), s y m pt o m, or disease ( ne w or 
e x acer bate d) te m p orall y ass ociate d wit h t he use of I P wit h o ut a n y j u dg m e nt o n ca usalit y.  
A n A E is c o nsi dere d “seri o us” if it: 
 Res ults i n d eat h  
 Is a life-t hr eate ni n g A E 
N ote:  A n A E is “life -t hr eate ni n g” if, i n t he vie w of t he I n v esti gat or or S p o ns or, its 
occ urre nce pla ces t h e s u bject at i m me diate ris k of deat h. It d oes n ot i ncl u de a n A E 
t hat, ha d it occ urre d i n a m ore se vere f or m, mi g ht ha ve ca use d death  
 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 p ersiste nt or si g nifica nt i nca p acit y or s u bsta ntial disr u pti o n of t he a bilit y t o 
c o n d uct n or mal life f u ncti o ns  
 Is a co n ge nital a n o mal y  or birt h defect  
Im p ort a 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 b e c o nsi dere d seri o us 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 s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve n t o n e of t hese o utc o mes . 
8. 2. 1. 2  Cl assific ati o n of A d verse E ve nts  
Se verit y of A d verse E ve nt s 
T he se verit y of a ll A Es will be assesse d b y t he I n vesti gat or a n d gra d e d as f oll o ws:  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 5  of 5 9  
 M il d: R e q uires mi ni mal or n o treat me nt a n d d o es n ot i nterfere wit h t he s u bject’s dail y 
acti vities 
 M o der ate:  R es ults i n a l o w le vel of i nc o n ve nie nce or c o ncer n a n d ma y ca use s o me 
i nterfere nce wit h f u ncti o ni n g 
 S e vere:  Interr u pts a s u bj ect’s us ual d ail y acti vit y a n d ma y re q uire s yst e mic dr u g t hera p y 
or ot her treat me nt. Se vere e ve nts are us uall y p ote ntiall y life -t hreate ni n g or i nca pacitati n g. 
T he ter m “se v ere” d oes n ot necessaril y e q u ate t o “seri o us .”  
Rel ati o ns hi p of A d verse E ve nts  
A ll A Es m ust ha ve t heir relati o ns hi p t o I P assesse d b y t h e I n v esti gat or w h o e x a mi nes a n d e val uates 
t he s u bject b as e d o n t e m p oral relati o ns hi p a n d  t h eir cli nical j u d g me nt. In a cli nical st u d y, t h e I P 
m ust al wa ys b e s us pect.  
T he rel ati o ns hi p of a n A E t o t he I P will be deter mi ne d usi n g t he b el o w cat e g ories. Fi nal 
deter mi nati o n of A E attri b uti o n a n d e x pecte d ness will be d eter mi ne d b y t h e S p o ns or i n 
c o ns ultati o n wit h t he Me dical M o nit or.  
 U nrel ate d:  T he A E is c o m pletel y i n d e pe n de nt of I P a d mi nistrati o n, a n d/ or e vi de nce e xists 
t hat t he e ve nt is defi nitel y relate d t o a n ot her eti ol o g y. T h ere m ust be a n alter nati ve, 
defi niti ve e ti ol o g y d oc u me nte d b y t h e I n vesti gat or. 
 U nli kel y:  A  cli nical e ve nt, i ncl u di n g a n a b n or m al la b orat or y test res ult, w h ose te m p oral 
relati o ns hi p t o I P ad mi nistrati o n ma kes a ca usal relati o ns hi p i m pr o ba ble (e. g., t he e v e nt 
di d n ot occ ur wit hi n a reas o na ble ti m e after a d mi nistrati o n of I P) a n d i n w hi c h ot her dr u gs 
or c he micals or u n derl yi n g diseas e pr o vi des pla usi ble e x pla nati o ns (e. g., t he s u bject’s 
cli nical c o n diti o n, ot her c o nc o mita nt treat me nts).  
 P ossi bl y: S o me e vi de nce t o s u g gest a ca usal relati o ns hi p (e. g. , t he e ve nt occ urre d wit hi n 
a reas o n a ble ti me after a d mi nistrati o n of I P). H o we ver, ot her fact ors ma y ha ve c o ntri b ute d 
t o t he e ve nt (e. g., t he s u bject’s cli nical c o n diti o n, ot her c o nc o mita nt e v e nts). 
 P r o b a bl y: E vi de n ce t o s u g gest a ca us al relati o ns hi p, a n d  t he i nfl ue nce of ot her fact ors is 
u nli kel y. T he cli nical e v e nt, i ncl u di n g a n a b n or m al la b orat or y test res ult, occ urs wit hi n a 
reas o na bl e ti me after a d mi nistrati o n of t he I P, is u nli kel y t o be attri b ute d t o c o nc urre nt 
disease or ot h er dr u gs or c he micals, a n d f oll o ws a cli nicall y reas o na ble res p o nse o n 
wit h dra wal.  
 D efi nitel y:  C lear e vi de n ce t o s u g gest a ca usal rel ati o ns hi p, a n d ot her p ossi ble c o ntri b uti n g 
fact ors ca n be r ule d o ut. T he cli nical e ve nt, i ncl u di n g a n a b n or mal la b orat or y test res ult, 
occ urs i n a pla usi ble ti me relati o ns hi p t o I P a d mi nistrati o n a n d ca n n ot be e x plai ne d b y 
c o nc urre nt dise ase or ot h er dr u gs or c h e micals. T he res p o nse t o wit h dra wal of t h e st u d y 
i nter ve nti o n ( dec h alle n ge) s h o ul d 
be cli nicall y 
pla usi ble. 
T he e v e nt 
m ust 
be 
p har mac ol o gic al l y or p h e n o me n ol o gicall y defi niti ve, wit h use of a satisfact or y rec h alle n ge 
pr oce d ure if necessar y.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 6  of 5 9  
E x pecte d ness  
A n A E or s us pecte d a d verse reacti o n is c o nsi dere d “ u ne x pecte d” if it is n ot liste d i n t he 
I n v esti gat or’s Br oc h ure, pac ka ge i nsert, or de vi ce la beli n g, if it is n ot liste d at t he s pecificit y or 
se verit y t hat has bee n o bser ve d, or if it is n ot co nsiste nt wit h t he ris k i nf or mati o n descri be d i n t he 
pr ot oc ol, as a me n de d. “ U ne x pecte d,” as use d i n t his defi niti o n, als o refers t o A Es or s us pecte d 
a d verse reacti o ns t hat are me nti o ne d i n t he I n vesti gat or’s Br oc h ure, pac ka ge i nsert, or de vice 
la beli n g as o cc urri n g wit h a cl ass of dr u gs  ( or ot her me dical pr o d ucts) or as a ntici pate d fr o m t he 
p har mac ol o gic al pr o perti es or ot her c haract eristics of t he I P, b ut are n ot s pecificall y m e nti o ne d as 
occ urri n g wit h t he p artic ular I P u n d er i n vesti gati o n.  
T he I n v esti gat or a n d c o ntract researc h or ga nizati o n, i n c o nj u ncti o n wit h t h e Me dical M o nit or a n d 
t he S p o ns or, will be res p o nsi ble f or det er mi ni n g w het her a n A E is u ne x pecte d (i.e., if t he nat ure, 
se verit y, or fre q u e nc y of t he e ve nt is n ot c o nsiste nt wit h t he ris k i nf or mati o n pre vi o usl y descri be d 
f or t he I P). 
8. 2. 1. 3  A d verse E ve nt Re p orti n g  Re q uire me nts  
A cc or di n g t o fe deral re g ulati o ns, a n I n vesti gat or m ust i m me diatel y re p ort  t o t he S p o ns or a n y S A E, 
w het her or n ot c o nsi dere d dr u g -relate d, i ncl u di n g t h ose liste d i n t he pr ot oc ol or I n v esti gat or’s 
Br oc h ure  a n d m ust i ncl u de a n assess me nt of w het her t here is a reas o n a ble p ossi bilit y t hat t he dr u g 
ca use d t he e ve nt.  
A cc or di n g t o fe deral  re g ulati o ns, t he S p o ns or m ust n otif y t he U S F o o d a n d Dr u g A d mi nistrati o n 
( F D A) an d all partici pati n g I n vesti gat ors as s o o n as p ossi ble, b ut i n n o case later t ha n 1 5 cale n dar 
da ys after t he S p o ns or det er mi nes t hat a p ote ntial s eri o us ris k arisi n g fr o m a cli nical st u d y q u alifies 
f or re p orti n g. S p o ns or m ust re p ort a n y s us pect e d a d verse reacti o n t hat is b ot h seri o us a n d 
u ne x pecte d. T he S p o ns or m ust re p ort a n A E as a s us pecte d a d verse reacti o n o nl y if t here is 
e vi de nce t o s u g gest a ca usal relati o ns hi p bet wee n t he dr u g a n d t he A E  ( See 2 1 C o de of Fe deral 
Re g ulati o ns [ C F R ] 3 1 2. 3 2 [c][1 ]). 
F urt her m ore, t he S p o ns or m ust als o n otif y F D A of a n y u ne x pecte d fatal or life -t hreate ni n g 
s us pecte d a d v erse reacti o n as s o o n as p ossi ble b ut i n n o case l ater t ha n 7 cale n dar da ys after t he 
S p o ns or ’s i nitial recei pt of t he i nf or mati o n ( See 2 1 C F R 3 1 2. 3 2[c][2 ]). 
8. 2. 1. 4  Pre g n a nc y  
In di vi d uals w h o are pre g na nt are n ot p er mitte d t o partici pate i n t he st u d y. A ll pre g na n cies are t o 
be re p orte d fr o m t he ti me i nf or me d c o nse nt is si g n e d u ntil t he e n d of t he st u d y ( Visit 7). S u bjects 
w h o re p ort b ec o mi n g pre g n a nt or h a vi n g a se x ual part ner ( W O C B P) w h o has bec o m e pre g n a nt 
will ha ve I P wit h dr a w n , will res u me sta n dar d of care treat me nt f or t heir c o n diti o n, a n d will 
u n der g o safet y f oll o w -u p visits a n d asse ss me nts. 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 7  of 5 9  
A n y re p ort of pre g n a nc y fr o m a s u bject m ust be re p orte d wit hi n 2 4 h o urs t o t he S p o ns or or its 
dele gate usi n g t he Pre g n a nc y Re p ort F or m . 
E ver y eff ort s h o ul d be m a de t o gat her i nf or mati o n re gar di n g t he pre g n a nc y o utc o me a n d c o n diti o n 
of t he i nfa nt. It is t he res p o nsi bilit y of t h e I n vesti gat or t o o btai n t his i nf or mati o n wit hi n 
a p pr o xi matel y 3 0 cale n d ar da ys after t he i nitial n otificati o n a n d a p pr o xi matel y 3 0 cale n dar da ys 
after deli ver y, if a p plica ble. 
P re g n a nc y c o m plicati o ns s uc h as s p o nta ne o us a b orti o n/ miscarria ge or c o n ge nital a b n or malit y are 
c o nsi dere d S A Es a n d m ust be re p orte d t o t he S p o ns or usi n g t he Seri o us A d verse E ve nt F or m. 
Electi ve a b orti o ns are n ot c o nsi dere d a n S A E . 
8. 2. 2  
He art R ate, Bl o o d Press ure, a n d O t her S afet y E v al u ati o ns 
S afet y e v al uati o ns will b e assess e d at t he ti me p oi nts i n dicate d o n t he Sc he d ule of Pr oce d ures a n d 
Assess me nts ( A p pe n di x 1 : Sc he d ule of Pr oce d ures a n d Ass ess me nt). A n a b bre vi ate d p h ysical 
e x a mi nati o n will be c o m plete d at Visit 1 ( Scree ni n g), a n d heart rate a n d bl o o d press ure will be 
c hec k e d . 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 8  of 5 9  
9  St atistic al C o nsi der ati o n s 
A  se parate Statistical A n al ysis Pla n ( S A P) will be pre pare d bef ore t he data base is l oc ke d a n d t he 
st u d y is u n mas ke d a n d will i nc l u de a m ore tec h nical a n d detaile d d escri pti o n of t he statistical 
a nal ys es descri be d i n t his secti o n. T his secti o n is a s u m mar y of t he pla n ne d statistical a nal ys es.  
C o nti n u o us meas ures will be s u m marize d descri pti vel y b y t he mea n, sta n dar d de viati o n, me dia n, 
a n d mi ni m u m  a n d ma xi m u m val ues. Cate g orical meas ures will be s u m marize d b y t h e fre q u e nc y 
a n d perce nta ge of s u bjects.  
9. 1  
St atistic al H y p ot hesi s 
T he pri mar y effic ac y e n d p oi nt is t he pr o p orti o n of s u bjects wit h A C C Gra de 0 i n t he st u d y e ye at 
Visit 6 ( Da y 1 4 ). 
T he N ull H y p ot hesis : At p ost-o perati ve Da y 1 4, t here is n o differe nce i n pr o p orti o n of s u bjects 
wit h A C C Gra de 0 i n t he st u d y e y e bet wee n a n acti ve tr eat me nt gr o u p  (V V N 4 6 1, 1. 0 % , or 
V V N 4 6 1, 0. 5 % ) a n d t he Ve hicle gr o u p . 
A lter n ati ve H y p ot hesis: At p ost -o perati ve Da y 1 4, t here is a differe nce i n pr o p orti o n of s u bjects 
wit h  A C C Gra de 0 i n t he st u d y e y e  bet wee n a n acti ve tr eat me nt gr o u p (V V N 4 6 1, 1. 0 % , or 
V V N 4 6 1, 0. 5 % ) a n d t he Ve hicle gr o u p . 
T he pri mar y h y p ot h esis f or t he st u d y is t h at at least o ne d ose re gi me n of V V N 4 6 1 is s u peri or t o 
Ve hicle wit h res pect t o t he pr o p orti o n of s u bjects wit h  A C C Gra de 0 i n t he st u d y e y e at Visit 6 
( Da y 1 4). 
F or t h e pri mar y e n d p oi nt , a se q ue ntial testi n g pr oce d ure will be e m pl o ye d t o c o ntr ol t h e o verall 
T y pe I err or rat e at t w o-si de d 5% wit h res pect t o m ulti ple c o m paris o ns f or t he f oll o wi n g 
h y p ot hes es: V V N 4 6 1, 1. 0 % , t o Ve hicle ( H1) a n d V V N 4 6 1, 0. 5 %, t o Ve hicle ( H2). T he testi n g 
pr oce d ure will b e d o ne i n a hierarc hical or der as H 1 a n d H 2. If H 1 is not si g nifica nt , t he n H 2 will 
n ot be teste d.  
9. 2  
S a m ple Size D eter mi n ati o n  
A sa m ple siz e of a p pr o xi matel y 9 0 c o m plete d s u bjects will be ra n d o mize d i n a 1: 1: 1 rati o t o 
V V N 4 6 1, 1. 0 %, V V N 4 6 1, 0. 5 %, a n d a matc hi n g Ve hicle t hat d oes n ot c o ntai n t he A PI. Wit h a 
sa m ple siz e i n eac h gr o u p of 3 0, t he st u d y will h a ve 8 0 % p o wer t o detect a differe nce of 3 5 %, 
ass u mi n g a res p o nse rate of 3 0 % i n t he Ve hicle gr o u p, a n d a t w o -si de d 0. 0 5 si g nifica nce le vel f or 
a Pears o n c hi -s q u are test. 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 3 9  of 5 9  
A dr o p -o ut rate of 1 0 % is ass u me d, res ulti n g i n a t otal sa m ple size of a p pr o xi matel y 1 0 2 s u bject s 
(3 4 f or V V N 4 6 1 , 1. 0 %, 3 4 f or V V N 4 6 1, 0. 5 %, a n d 3 4 f or Ve hicl e). 
9. 3  
A n al ysis P o p ul ati o n s 
T he F ull A nal ysis Set ( F A S) will c o nsist of all s u bjects w h o are ra n d o mize d. S u bjects will be 
a nal yze d i n t he gr o u p  t o w hic h t he y are ra n d o mize d. T his set will be use d f or t he a nal ysis of all 
effic ac y e n d p oi nts as t he pri mar y a nal ysis.  
T he Per Pr ot oc ol ( P P) A nal ysis Set is a s u bset of t he F A S a n d will i ncl u de all s u bjects i n t he F A S 
w h o c o m plete st u d y -re q uire d treat me nt a n d 
w h o f oll o w t he pr ot oc ol 
wit h o ut si g nifica nt 
de viati o ns. T he deter mi nati o n of si g nifica nt pr ot o c ol de viati o ns will be ma de bef ore dat a base l o c k 
a n d u n mas ki n g.  
T he Safet y A nal ysis Set ( S A F) will i ncl u de all s u bjects w h o recei v e at least o ne d ose of I P,  as 
i n dicate d o n t he d osi n g rec or d. S u bjects will be a nal yze d i n t he gr o u p acc or di n g t o t he treat me nt 
recei v e d. All safet y vari a bles will be a n al yze d usi n g t he S A F, a n d o nl y o bser ve d d ata will be 
i ncl u de d (i.e., missi n g data will re mai n missi n g f or t he safet y a nal ysis).  
9. 4  
St atistic al A n al yses  
T he statistical a nal yses of t he st u d y will be perf or m e d o n t he dat a t hr o u g h Da y 2 1, after all s u bjects 
ha ve eit her c o m plete d t h e Da y 2 1 visit or disc o nti n ue d earl y fr o m t he st u d y , a n d after t he st u d y 
data base h as bee n cl ea n e d, verifi e d, a n d l oc ke d. It is pla n ne d t hat t he d ata fr o m all sites t hat 
partici pate i n t he st u d y will be c o m bi ne d s o t hat t he tar get sa m ple siz e will be a v aila ble f or 
a nal ysis.  
9. 4. 1  
B aseli ne Descri pti ve A n al yse s 
D e m o gra p hic c h aracteristics , i ncl u di n g a ge (years), se x, race, et h nicit y, a n d ot her b aseli ne 
c haracteristics , will be s u m marize d descri pti vel y b y treat me nt gr o u p a n d o v erall. Me dical hist or y 
(c o de d usi n g the 
M e di cal Dicti o nar y f or Re g ulat or y Acti vities [ Me d D R A]) a n d pri or a n d 
c o nc o mita nt me dicati o ns  (c o de d usi n g W H O Dr u g ) will be s u m marize d b y treat me nt a n d o verall.  
T he n u m bers of s u bjects w h o were e nr olle d a n d c o m plete d eac h visit of t he st u d y will be pr o vi de d, 
as well as t h e reas o ns f or all e nr oll me nt disc o nti n uati o ns, gr o u pe d b y maj or reas o ns ( e. g., l ost t o 
f oll o w-u p). A list of dis c o nti n ue d s u bjects, pr ot o c ol de viati o ns, a n d s u bjects e x cl u de d fr o m t he 
a nal ysis s ets will be pr o vi de d as well . 
E x p os ure t o I P a n d a d h ere nce t o t he d osi n g sc h e d ule will be s u m marize d b y treat me nt a n d o verall.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 0  of 5 9  
9. 4. 2  
Effic ac y A n al yses  
S u m mar y d escri pti ve st atistics will be prese nt e d f or all st u d y visits at w hic h efficac y data are 
c ollecte d. Effi cac y a n al yses will be prese nte d f or t he st u d y e ye a n d will o nl y i ncl u de data  fr o m 
bef ore t he earliest o bs er ve d i nsta nce of resc u e t hera p y. I n ot her w or ds, d at a t hat occ urs after t he 
earliest o bser ve d res c ue t hera p y will be set t o missi n g . 
Efficac y a nal yses will be c o n d ucte d usi n g t he F A S , i n ge neral, a n d se nsiti vit y a nal ys es f or pri mar y 
a n d sec o n dar y e n d p oi nts will be c o n d ucte d usi n g t he P P A nal ysis Set . 
9. 4. 2. 1  Pri m ar y Effic ac y A n al yses  
Pri mar y Esti ma n d : T he pri mar y esti ma n d is tr eat me nt differe nce bet wee n V V N 4 6 1 ( 1. 0 % or 
0. 5 %) a n d t he Ve hicle i n t he pr o p orti o n of s u bjects wit h A C C Gra de 0 at Visit 6 ( Da y 1 4) i n t he 
st u d y e ye usi n g t he F A S. 
Tar ge t P o p ulati o n: S u bjects u n der g oi n g r o uti ne cataract s ur ger y w h o meet t he st u d y e ntr y criteria .  
E n d p oi nt : Pr o p orti o n of s u bjects wit h A C C Gra de 0 i n t he st u d y e ye at Visit 6 ( Da y 1 4) . 
Treat me nt C o n diti o n : Treat me nt c o n diti o n is base d o n ra n d o mize d treat me nt. 
P o p ulati o n -Le v el S u m mar y : T h e differe nce i n pr o p orti o ns i n s u bjects wit h A C C Gra de 0 i n t he 
st u d y e ye at Visit 6 ( Da y 1 4) a n d t he c orres p o n di n g p-v al ue . 
I nterc urre nt E ve nts a n d Strate gies t o A d dress I nterc urre nt E v e nts 
 Disc o nti n uati o n of st u d y t hera p y wit h c o nti n ue d p artici pati o n i n t he st u d y wit h o ut recei pt 
of resc u e t hera p y  
o  Treat me nt P olic y A p pr oac h –  n o i m p utati o n; use o bser ve d dat a  
 Recei pt of res c ue t hera p y (t o pical c ortic oster oi d) i n t he st u d y e ye  
o  C o m p osite A p pr oac h –  s u bjects w h o recei ve resc ue t hera p y at or bef ore t he 
assess me nt visit will be ass u me d t o ha ve faile d t he pri mar y e n d p oi nt  
 Missi n g data wit h or wit h o ut wit h dra wal, re gar dl ess of reas o n  
o  H y p ot hetic al A p pr oac h –  n o i m p utati o n; a nal ysis will be base d o n s u bjects w h o 
ha ve a n e val ua ble  a nteri or c ha m ber i n t he st u d y e ye at Visit 6 ( Da y 1 4)  
Pears o n’s c hi -s q uare will be use d t o test t he pri mar y e n d p oi nt b et wee n t he 2 differe nt d oses of 
V V N 4 6 1 vs t he Ve hi cle. T he pri mar y a n al ysis will als o be perf or me d o n t h e P P A nal ysis Set.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 1  of 5 9  
9. 4. 2. 2  Sec o n d ar y Effi c ac y A n al yses  
T he sec o n dar y efficac y e n d p oi nts will i ncl u de t he pr o p orti o n of s u bjects wit h A C C Gra de 0, t he 
pr o p orti o n of s u bjects wit h A C F Gra de 0, a n d t he pr o p orti o n of s u bjects re q uiri n g resc u e 
me dicati o n. T hes e e n d p oi nts will be a n al yze d re gar dl ess of  t he si g nifi ca nce of t he pri mar y 
e n d p oi nt a nal ysis.  
9. 4. 3  
S afet y A n al yses  
S afet y a n al yses will be perf or me d o n all s u bjects i n t he S A F. T he assess me nt of safet y will be 
base d o n t he s u m mar y of oc ular a n d n o n -o c ular A Es, B C V A, a n d o p ht hal mic e x a mi nati o ns usi n g 
slit la m p bi o micr osc o p y a n d dilate d o p ht hal m osc o p y. S u m maries will be pr o vi de d b y treat me nt 
gr o u p a n d, f or oc ular assess me nts, se paratel y b y e ye.  
9. 4. 3. 1  A d verse E ve nt s 
A Es will be c o de d usi n g Me d D R A  a n d c ate g orize d b y s yste m or ga n class usi n g preferre d ter ms. 
Se parate s u m maries of A Es relate d t o treat me nt (as re p orte d b y t he I n vesti gat or) a n d b y se v erit y 
will be prese nte d. T he n u m ber of deat hs a n d S A Es will als o be prese nte d, a n d e ve nts lea di n g t o 
disc o nti n uati o n fr o m t he st u d y will be liste d a n d t a b ulate d.   
9. 4. 3. 2  Cl i nic al L a b or at or y Tests 
T here will n ot be a n y a nal ysis of c li nical la b orat or y dat a. Uri ne pre g na n c y tests will be c o n d ucte d 
at Visit 1 ( Scree ni n g), Visit 2 ( Da y of S ur ger y; D a y 0), Visit 6 ( Da y 1 4), a n d Visit 7 ( Da y 2 1) f or 
W O C B P . Res ults of uri ne pre g na n cy tests  will be prese nte d i n a listi n g.  
9. 4. 3. 3  Ot her S afet y E v al u ati o ns  
S u m mar y statistics f or o bser ve d a n d C F B  f or B C V A a n d I O P w ill be pres e nte d. A b n or malities i n 
slit la m p bi o micr osc o p y a n d dilate d o p ht hal m osc o p y will be s u m marize d b y fre q ue nc y a n d 
perce nt a ge.  T he fre q ue n c y a n d pr o p orti o n of s u bjects treate d wit h resc u e me dicati o ns will be 
s u m marize d. 
He art R ate a n d Bl o o d Press ure  
H eart rate a n d bl o o d press ure  will be a ssesse d d uri n g scree ni n g. T hes e meas ure me nts will be 
prese nte d i n a listi n g. 
P h ysic al E x a mi n ati o ns  
A n a b bre viate d p h ysical e x a mi nati o n  w ill be c o n d ucte d d uri n g scree ni n g . The res ults will be 
s h o w n i n a listi n g. 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 2  of 5 9  
9. 5  
I nteri m A n al ysis 
N o i nteri m a nal ysis is pla n ne d f or t he st u d y. 
9. 6  
S u b gr o u p A n al yses  
S u b gr o u p  a nal ys es ma y b e c o n d ucte d base d o n  bas eli ne s u bject c haracteristi cs  o n a p ost h oc basis.  
9. 7  
E x pl or at or y A n al yses  
E x pl orat or y e n d p oi nts will be a nal yze d i n a ma n ner si milar t o t he sec o n dar y e n d p oi nts. Mea n C F B 
i n A C C Gra de a n d A C F Gra de will be a nal yz e d usi n g mi x e d m o del re peate d meas ures. T he m o del 
will i ncl u de treat me nt, visit, a n d treat me nt b y visit i nteracti o n as fi x e d effects a n d a c o variate f or 
baseli ne meas ur e me nt ( w here a p pr o priat e) wit h a ra n d o m effect f or site. A n u nstr uct ure d 
c o varia n ce a m o n g re p eate d meas ur e me nts will be ass u me d. O n l y d ata fr o m bef ore t he use of 
resc ue me dicati o n will be i ncl u de d i n t hese a nal ys es. T he pr o p orti o n of s u bjects wit h n o p ost-
o perati ve oc ular pai n i n t he st u d y e ye at Visit 5 ( Da y 7) a n d Visit 6 ( Da y 1 4) will als o be a nal yze d.  
9. 8  
Missi n g, U n use d, or S p uri o us D at a  
M issi n g data f or c o nti n u o us e n d p oi nts will be c o nsi dere d missi n g at ra n d o m wit h t he a n al ysis 
usi n g mi x e d m o del re peate d meas ures . Ot her wise, o bser ve d dat a will be a n al yze d at eac h visit. 
9. 9  
T a b ul ati o n of I n di vi d u al S u bject D at a  
All data c ollecte d i n t he st u d y will be pres e nte d i n i n di vi d ual s u bject data listi n gs f or all s u bjects.  
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 3  of 5 9  
1 0  S u p p orti n g D oc u me nt ati o n a n d O per ati o n al C o nsi der ati o ns  
1 0. 1  Re g ul at or y Iss ues, Et hic al C o ncer ns, a n d St u d y O versi g ht  
1 0. 1. 1  
I nf or me d C o nse nt Pr ocess 
1 0. 1. 1. 1  C o nse nt/ Asse nt D oc u me nt s 
C o nse nt f or ms descri bi n g i n detail t he st u d y i nter ve nti o n, st u d y pr oce d ures, a n d ris ks will be gi ve n 
t o t he s u bject, a n d writte n d oc u me ntati o n of i nf or me d c o nse nt a n d pri vac y a ut h orizati o n will be 
re q uire d b ef ore starti n g i nter ve nti o n/a d mi nisteri n g I P. T h e writte n c o ns e nt d oc u me nt will e m b o d y 
t he ele me nts of i nf or me d c o nse nt as descri be d b y t h e I nter n ati o nal C o u ncil f or Har m o nisati o n 
(I C H) a n d will als o c o m pl y wit h l ocal r e g ulati o ns. 
If a p pr o priate a n d re q uir e d b y t he l ocal I nstit uti o nal Re vie w B o ar d (I R B), asse nt fr o m t he s u bject 
will als o be o btai ne d. If a s u bject is u na ble t o si g n t he i nf or me d c o nse nt f or m, a le gal re prese nt ati ve 
ma y si g n f or t he m.  
1 0. 1. 1. 2  C o nse nt Pr oce d ures a n d D oc u me nt ati o n  
Inf or me d c o nse nt is a pr ocess t hat is i nitiate d bef ore a pr os pecti ve s u bject a gr ees t o p artici pate i n  
a cli nical st u d y, a n d t his pr ocess c o nti n ues t hr o u g h o ut s t u d y p artici pati o n. I nf or me d co nse nt f or ms 
will be a p pr o ve d b y t he I R B, a n d t h e s u bject w ill be as ke d t o rea d a n d re vie w t he d o c u me nt. T h e 
I n v esti gat or will e x plai n t he res earc h st u d y t o t h e s u bject a n d a ns wer a n y q u esti o ns t hat ma y arise. 
A ver bal e x pla nati o n will be pr o vi de d i n ter ms s uite d t o t he s u bject’s c o m pre he nsi o n of t he 
p ur p oses, pr o ce d ures, a n d p ote ntial ris ks of t he st u d y a n d of  t h eir ri g hts as a res earc h s u bject. T h e 
su bject  will ha ve t he o p p ort u nit y t o caref ull y re vi e w t he writte n c o nse nt f or m a n d as k q uesti o ns 
bef ore s i g ni n g. T he s u bject sh o ul d ha ve t he o p p ort u nit y t o disc uss t he  st u d y wit h t heir fa mil y or 
s urr o gates or t hi n k a b o ut it bef ore a greei n g t o partici pate  i n t he st u d y. T he s u bject will si g n a n d 
date t he i nf or me d c o ns e nt f or m bef ore an y pr oce d ures are do ne s pecificall y f or t he st u d y.  T h e 
su bject  m ust be i nf or me d t hat part ici pati o n is v ol u ntar y a n d t hat t he y ma y wit h dra w fr o m t he st u d y 
at a n y ti me, wit h o ut prej u dice. A c o p y of t he si g ne d a n d dat e d i nf or m e d c o nse nt f or m will be gi ve n 
t o t he s u bject f or t heir rec or ds. T he i nf or me d c o nse nt pr ocess will be c o n d ucte d a n d d oc u me nte d 
i n t he s o urce d oc u me nt (i ncl u di n g t he date), a n d t he f or m si g ne d a n d date d, bef ore t he s u bject 
u n der g oes a n y st u d y -s p ecific pr oce d ures. T h e ri g hts a n d welfare of t he s u bject will be pr otect e d 
b y e m p hasizi n g t o t he m t hat t he q ualit y of t heir m e dical car e will n ot be a d versel y affecte d if t he y 
decli ne t o partici pat e i n t he st u d y.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 4  of 5 9  
1 0. 1. 2  
St u d y Disc o nti n u ati o n a n d Cl os ur e 
T he  st u d y ma y b e te m p oraril y s us pe n de d or pre mat urel y ter mi nate d if t here is s ufficie nt reas o n a ble 
ca use. Writte n n otificati o n, d oc u me nti n g t he reas o n f or st u d y s us p e nsi o n or ter mi nati o n, will b e 
pr o vi de d b y t h e s us pe n di n g or ter mi nati n g part y t o  s u bjects, I nv esti gat ors, f u n di n g a ge nc y  (if 
a p plica ble), t he S p o ns or , a n d re g ulat or y a ut h orities . If t he st u d y is pre m at urel y ter mi nate d or 
s us pe n de d, t he I n v esti gat or will pr o m ptl y i nf or m s u bjects, t he I R B, a n d t he S p o ns or a n d will 
pr o vi de t he reas o n(s) f or t he ter mi nati o n or s us pe nsi o n. S u bject s will be c o ntacte d, as a p plica ble, 
a n d be i nf or me d of c ha n ges t o visit sc he d ule s. 
Circ u msta nces t hat ma y warra nt ter mi nati o n or s us pe nsi o n ma y i ncl u d e, b ut are n ot li mite d t o:  
 Deter mi nati o n of u ne x pecte d, si g nifi ca nt, or u nacce pta ble ris k t o s u bjects 
 I ns ufficie nt c o m plia n ce wit h pr ot oc ol re q uire me nts  
 Data t hat are n ot s uffici e ntl y c o m plete a n d/ or e val ua ble  
 Deter mi nati o n of f utilit y  
T he s t u d y ma y res u me o nce c o n cer ns a b o ut safet y, pr ot o c ol c o m plia nce, a n d data q ualit y are 
a d dresse d a n d satisf y t he S p o ns or, I R B , a n d/ or F D A . 
1 0. 1. 3  
C o nfi de nti alit y a n d Pri v ac y  
S u bject  c o nfi de ntialit y a n d pri vac y will be strictl y hel d i n tr ust b y t he partici pati n g I n vesti gat ors, 
st u d y pers o n n el, an d t he S p o ns or(s) a n d t heir i nter ve nti o ns. T his c o nfi de ntialit y will be e xte n de d 
t o c o ver cli nical i nf or mati o n relati n g t o s u bjects. T heref ore, t he st u d y pr ot oc ol, d oc u me ntati o n, 
data, a n d all ot her i nf or mati o n ge nerate d will be hel d i n strict c o nfi d e nce. N o i nf or m ati o n 
c o ncer ni n g t he st u d y or t he st u d y d ata w ill be release d t o a n y u n a ut h orize d t hir d part y wit h o ut 
a d va nce d w ritte n a p pr o val of t he S p o ns or.  
A ll researc h acti vities will be c o n d ucte d i n as pri v ate a setti n g as p ossi ble.  
T he St u d y M o nit or, ot her a ut h or iz e d re pres e ntati ves of t he S p o ns or, re prese ntati ves of t h e I R B, 
re g ulat or y a ge n cies, a n d t he p har mace utical c o m pa n y s u p pl yi n g I P will be a ble t o i ns pect all 
d oc u me nts a n d rec or ds re q uire d t o be mai ntai ne d b y t he I n vesti gat or, i ncl u di n g, b ut n ot li mite d t o , 
me dical rec or ds (i.e., offi ce, cli nic, or h os pital) a n d p har mac y rec or ds f or t h e s u bjects i n t he st u d y. 
Sites will per mit access t o s uc h rec or ds.  
T he st u d y s u bject’s c o nta ct i nf or mati o n will be sec urel y st or e d at eac h site f or i nter nal use d uri n g 
t he st ud y. At t he e n d of t he st u d y, all rec or ds will c o nti n ue t o be k e pt i n a sec ure l ocati o n f or as 
l o n g a p eri o d as dictat e d b y t he re vie wi n g I R B, I nstit uti o nal p olicies, or S p o ns or re q uire m e nts.  
S t u d y s u bj ect res earc h d ata, w hic h is f or p ur p oses of statistical a nal ysis a n d scie ntific re p orti n g, 
will be tra ns mitte d t o a n d st ore d i n a n electr o nic data ca pt ur e s yste m. T his will n ot i ncl u de t he 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 5  of 5 9  
s u bject’s c o nt act or i de ntif yi n g i nf or mati o n. Rat her, i n di vi d ual s u bjects a n d t heir res earc h d ata 
will be i de ntifie d b y a  u ni q ue st u d y i de ntificati o n n u m ber. T he st u d y data e ntr y a n d st u d y 
ma na ge me nt s yste ms use d b y sites a n d b y c o ntract researc h or ga nizati o n st u d y p ers o n nel will be 
sec ure d a n d pass w or d pr otecte d.  
1 0. 1. 4  
Ke y R ol es a n d St u d y G o ver n a nce  
T a ble 2  
St u d y A d mi nistr ati ve Str uct ure  
Title/ R ole  
C o nt act I nf or m ati o n  
S p o ns or:  
Vi va Visi o n Bi otec h ( H o n g K o n g) Li mite d  
 
 
 
 
 
C hief Me dic al Officer:  
 
 
 
 
 
Me dic al M o nit or:  
 
 
 
 
 
 
  
C o ntr act Rese a rc h Or g a niz ati o n:  
 
 
 
 
1 0. 1. 5  
Cli nic al M o nit ori n g  
L e xitas P har ma Ser vices, I nc., will c o n d uct t he cli nical m o nit ori n g f or t he st u d y. A cli nical 
m o nit ori n g pla n ma y b e use d a n d will descri be i n detail w h o will c o n d uct t he m o nit ori n g, at w hat 
fre q ue n c y m o nit ori n g will be d o ne, at w hat le vel of detail m o nit ori n g will be perf or me d, a n d t he 
distri b uti o n of m o nit ori n g re p orts.  
1 0. 1. 6  
Q u alit y Ass ur a nce a n d Q u alit y C o ntr ol  
E ac h site will perf or m i nter nal q ualit y ma na ge me nt of st u d y c o n d u ct, data , a n d d oc u me ntati o n a n d 
c o m pleti o n. A n i n di vi d ualize d q ualit y ma na ge m e nt pla n ma y be  de vel o p e d t o descri be a site’s 
q ualit y ma na ge me nt.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 6  of 5 9  
Q ualit y c o ntr ol  p r oce d ures will be i m ple me nte d be gi n ni n g wit h t he dat a e ntr y s yste m, a n d data 
q ualit y c o ntr ol c hec ks t hat will be r u n o n t he data base will be ge n erat e d. A n y missi n g data or d ata 
a n o malies will be c o m m u nicate d t o t he site(s) f or clarificati o n/res ol uti o n.  
F oll o wi n g writte n Sta n dar d O perati n g Pr oce d ures , the m o nit ors will verif y t hat t he cli nical st u d y 
is c o n d ucte d, a n d d ata are ge n erate d , d oc u me nt e d (rec or de d), a n d re p orte d i n c o m plia nce wit h t he 
pr ot oc ol, I C H Go o d Cli nical Practice  (G C P ), a n d a p plica ble re g ulat or y re q uire me nts (e. g., G o o d 
La b orat or y Practice [ G L P ], G o o d Ma n ufact uri n g Practice [G M P ]).  
T he site will pr o vi de direct access t o all st u d y-relat e d sites, s o urce dat a/ d oc u me nts, a n d re p orts f or 
t he p ur p ose of m o nit ori n g a n d a u diti n g b y t h e S p o ns or, a n d i ns pe cti o n b y l ocal a n d re g ulat or y 
a ut h orities.  
1 0. 1. 7  
D at a H a n dli n g a n d Rec or d Kee pi n g  
1 0. 1. 7. 1  D at a C ollecti o n a n d M a n a ge me nt Res p o nsi bilities  
D ata c ollecti o n is t he res p o nsi bilit y of st u d y pers o n nel at t he site u n der t he s u per visi o n of t he site’s 
I n v esti gat or. T he I n v esti gat or is res p o nsi ble f or e ns uri n g t he acc urac y, c o m plete ness, le gi bilit y, 
a n d ti meli ness of t he data re p orte d . 
All s o urce d oc u m e nts s h o ul d be c o m plete d i n a neat, l e gi ble ma n ner t o ens ure acc urate 
i nter pretati o n of dat a. 
C o pies of t he st u d y visit w or ks heets ma y be pr o vi de d f or use as s o urce d oc u me nt w or ks heets f or 
rec or di n g data f or eac h s u bject e nr olle d i n t he st u d y. Data rec or de d i n t h e e C R F d eri v e d fr o m 
s o urce d oc u m e nts s h o ul d be c o nsiste nt wit h t he data rec or de d o n t he s o urce d oc u me nts.  
C li nical data (i ncl u di n g A Es, c o nc o mita nt me dicati o ns, a n d e x pecte d a d v erse reacti o ns data) w ill 
be e ntere d i nt o  a n electr o nic data ca pt ure s y ste m pr o vi de d b y Le xitas P har ma Ser vices, I nc. T he 
electr o nic dat a ca pt ur e s yste m will be c o m plia nt wit h  2 1 C F R Part 1 1. T he data s yste m i ncl u des 
pass w or d pr otecti o n a n d i nter nal q ualit y c h ec ks, s uc h as a ut o matic ra n ge c hec ks, t o i d e ntif y data 
t hat a p pear i nc o nsiste nt, i nc o m plete, or i n acc urate. Cli nical data will be e ntere d directl y fr o m t h e 
s o urce d oc u m e nts. 
1 0. 1. 7. 2  St u d y Rec or ds Rete nti o n  
S t u d y d oc u me nts s h o ul d be ret ai ne d f or a mi ni m u m of 2 years after t he last a p pr o val of a mar keti n g 
a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o pe n di n g or c o nte m plate d mar keti n g a p plicati o ns 
i n a n I C H re gi o n or u ntil at least 2 years ha v e ela pse d si nce t he f or mal disc o nti n uati o n of cli nical 
de vel o p me nt of t he st u d y i nter ve nti o n. T hese d o c u me nts s h o ul d be retai n e d f or a l o n ger p eri o d, 
h o we ver, if re q uire d b y l ocal re g ulati o ns. N o rec or ds will be destr o ye d wit h o ut a d va nce w ritte n 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 7  of 5 9  
c o nse nt of t h e S p o ns or, if a p plica bl e. It is t he res p o nsi bilit y of t he S p o ns or t o i nf or m t he 
In v esti gat or w he n t hes e d oc u me nts n o l o n ger nee d t o be  retai ne d.  
1 0. 1. 8  
P r ot oc ol D e vi ati o ns  
A  pr ot oc ol de viati o n is a n y n o n -c o m plia nce wit h t he cli nical st u d y pr ot oc ol, I C H G C P, or Ma n ual 
of Pr oce d ures  re q uir e me nts. The n o n -c o m plia nce ma y be o n t he p art of t he s u bject, t he 
In v esti gat or, or t he st u d y pers o n nel. As a res ult of de viati o ns, c orrecti ve acti o ns are t o be 
de vel o pe d b y t he site a n d i m ple me nte d pr o m ptl y.  
T hese practices are c o nsiste nt wit h I C H G C P:  
 4. 5 C o m plia nce wit h Pr ot oc ol, secti o ns 4. 5. 1, 4. 5. 2, a n d 4. 5. 3  
 5. 1 Q ualit y Ass ura nce a n d Q ualit y C o ntr ol, se cti o n 5. 1. 1  
 5. 2 0 N o n -c o m plia nce, s ecti o ns 5. 2 0. 1, a n d 5. 2 0. 2.  
It is t he I n v esti gat or’s res p o nsi bilit y t o us e c o nti n u o us vi gila nce t o i d e ntif y a n d re p ort pr ot oc ol 
de viati o ns . All pr ot oc ol de viati o ns m ust be a d dresse d i n st u d y s o urce d oc u me nts  a n d re p ort e d t o 
t he S p o ns or a n d t he re vie wi n g I R B per t heir p olici es. The In vesti gat or is res p o nsi ble f or k n o wi n g 
a n d a d heri n g t o t he re vie wi n g I R B ’s re q uire me nts. 
1 0. 1. 9  
P u blic ati o n a n d D at a S h ari n g P olic y  
T he  st u d y will c o m pl y wit h t he C li nical Trials Re gistrati o n a n d Res ults I nf or mati o n S u b missi o n 
r ule. As s uc h, t he st u d y will be re gistere d at Cli nical Trials. g o v, a n d t he res ults fr o m t he st u d y will 
be s u b mitte d t o Cli nical Trials. g o v. I n a d diti o n, e ver y atte m pt will be ma de t o p u blis h res ults i n 
peer -re vie we d j o ur nals. 
T he i nstit uti o ns a n d I n vesti gat ors p artici pati n g i n t h e st u d y s hall h a ve n o ri g ht t o p u blis h or prese nt 
t he res ults of t he st u d y wit h o ut a d va nce writte n c o nse nt fr o m t he S p o ns or. 
1 0. 1. 1 0  C o nflict of I nterest P oli c y  
T he i n de pe n de n ce of t he st u d y fr o m a n y act ual or percei ve d i nfl ue nce, s uc h as b y t he 
p har mace utical i n d ustr y, is critical. T heref ore, a n y act ual c o nflict of i nterest of pers o ns w h o ha ve 
a r ole i n t he desi g n, c o n d uct, a nal ysis, p u blicati o n, or a n y as pect of t he st u d y will be discl ose d a n d 
ma na ge d. F urt h er m ore,  p ers o ns w h o ha v e a percei ve d c o nflict of i nterest will be re q uire d t o ha v e 
s uc h c o nflicts ma na ge d i n a wa y t hat is a p pr o priat e t o t heir partici pati o n i n t he desi g n a n d c o n d uct 
of t he st u d y.  

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 8  of 5 9  
1 1  R efere nces 
J a bs D A, N usse n blatt R B, & R ose n b a u m J T; Sta n dar dizati o n of U veitis N o me nclat ure ( S U N) 
W or ki n g Gr o u p. Sta n dar diz ati o n of u veitis n o me nclat ure f or re p orti n g cli nical data. Res ults of t he 
First I nter n ati o nal W or ks h o p. A meric a n J o ur n al of O p ht h al m ol o gy . 2 0 0 5; 1 4 0( 3): 5 0 9-5 1 6.  
Ki m T, Sall K, H olla n d EJ, Brazzell R K, C o ultas S, & G u pta P K. Safet y a n d efficac y of t wice 
dail y a d mi nistrati o n of K PI -1 2 1 1 % f or oc ular i nfl a m mati o n a n d pai n f oll o wi n g cataract s ur ger y. 
Cli nic al O p ht h al m ol o gy . 2 0 1 9; 1 3: 6 9-8 6.  
O’ S hea JJ, Sc h wartz D M, Villa ri n o A V, Ga di na M, McI n n es I B, & La ure nce A. T he J A K-S T A T 
pat h wa y: I m p act o n h u ma n disease a n d t hera pe utic i nter ve nti o n. A n n u al Revie w of Me dici ne . 
2 0 1 5; 6 6: 3 1 1 -3 2 8.  
Star k G R & Dar nell J E Jr. T he J A K -S T A T pat h w a y at t we nt y. I m m u nity. 2 0 1 2; 3 6( 4): 5 0 3-5 1 4.  
Vil lari n o A V, Ka n n o Y, Fer di na n d J R, & O’ S h ea JJ. Mec ha nis ms of Ja k/ S T A T si g nali n g i n 
i m m u nit y a n d disease. J o ur n al of I m m u n ol o gy . 2 0 1 5; 1 9 4( 1): 2 1-2 7.  
We n J, H u H, C he n M, Ya n g H, Z h a o Y, & Li u Y. R ole of J a n us ki nase (J A K) i n hi bit or i n 
a ut oi m m u ne oc ular i nfl a m mati o n: A s yst e matic re vi e w. 
J o ur n al of I m m u n ol o gy Res e arc h . 
2 0 2 1; 2 0 2 1: 2 3 2 4 4 0 0.  
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 4 9  of 5 9  
1 2  A p pe n di ces 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 0  of 5 9  
1 2. 1  A p pe n di x 1: Sc he d ule of Pr oce d ures a n d Assess me nt s 
St u d y Peri o d  
Scree ni n g  
C at ar act 
S ur ger y  
Tre at me nt Peri o d  
E n d of 
Tre at me nt  
E n d of 
St u d y  
Visit N o.  
1  
2  
3  
4  
5  
6  
7  
St u d y D a y  
D a y -3 0 t o -1  
D a y 0  
D a y 1  
D a y 3 ± 1  
D a y 7 ± 1  
D a y 1 4 ± 2  
D a y 2 1 ± 2  
I nf or me d c o nse nt/ Asse nt 
X  
 
 
 
 
 
 
I ncl usi o n/ E xcl usi o n criteria 
X  
 
X 1 
 
 
 
 
De m o gra p hics  
X  
 
 
 
 
 
 
Me dical/ Oc ular/ S ur gical hist or y  
X  
 
 
 
 
 
 
Heart rate a n d bl o o d press ure  
X  
 
 
 
 
 
 
A b bre viate d p h ysical e xa mi nati o n  
X  
 
 
 
 
 
 
Uri ne pre g na nc y test  
X  
X  
 
 
 
X  
X  
Pri or/ C o nc o mita nt me dicati o ns  
X  
X  
X  
X  
X  
X  
X  
S u bj ect a d mi nistrati o n of test e ye dr o p  
X  
 
 
 
 
 
 
Ra n d o mizati o n  
 
 
X  
 
 
 
 
Dis pe nse I P  
 
 
X  
 
X  
 
 
C ollect u n use d I P  
 
 
 
 
X  
X  
 
I n-cli nic a d mi nistrati o n of I P  
 
 
X  
 
 
 
 
P ai n sc ore trai ni n g  
X  
 
X  
 
 
 
 
N P R S  
 
 
X  
X  
X  
X  
 
D osi n g a d here nce  
 
 
 
X  
X  
X  
 
A E m o nit ori n g  
 
X  
X  
X  
X  
X  
X  
Slit la m p bi o micr osc o p y  
X  
 
X  
X  
X  
X  
X  
B C V A  
X  
 
X  
X  
X  
X  
X  
I O P 
X  
 
X  
X  
X  
X  
X  
Dilate d o p ht hal m osc o p y  
X  
 
 
 
 
 
X  
A b bre viati o ns: 
A C C =a nteri or c ha m ber cell; 
A E =a d verse e ve nt; B C V A = b est correcte d v is ual ac uit y; C E L R =cat aract e xtracti o n a n d le ns re place me nt; 
I O P =i ntra o c ular press ure; I P =i n vesti gati o nal pr o d uct; N P R S = N u meric P ai n Rati n g Scale  
1Incl usi o n a n d e xcl usi o n criteria will be assesse d at Visit 1 ( Scree ni n g) ; s u bj ects w h o meet eli gi bilit y re q uire me nts at Visit 1 ( Scree ni n g) will c o nti n ue t o be eli gi ble 
f or st u d y partici pati o n if t he y prese nt at Visit 3 ( Baseli ne/ Ra n d o mizati o n ) wit h  A C C i nfla m mati o n ≥2 i n t he st u d y e ye  after ha vi n g c o m plete d C E L R s ur ger y  
at Visit 2 ( Da y of S ur ger y) wit h o ut s ur gical c o m plicati o n s. 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 1  of 5 9  
1 2. 2  A p pe n di x 2: W o m a n of C hil d be ari n g P ote nti al ( W O C B P)  
P re g n a nc y or ref us al t o a d here t o c o ntrace pti o n re q uire ments is e x cl usi o nar y . 
Fe male s u bjects a n d fe m ale part ners of male s u bjects are c o nsi dere d of n o n -c hil d beari n g p ote ntial 
if t he y ha v e bee n i n me n o pa use f or at l east 1 year, ha ve h a d a t u bal li gati o n at least 1 year b ef ore 
Visit 1 ( Scree ni n g) , or h a ve ha d a t otal h ysterect o m y. C o ntrace pti o n is n ot re q uire d d uri n g t he 
st u d y f or t h ose of n o n-c hil d beari n g p ot e ntial.  
Se x uall y acti ve fe male s u bjects of c hil d beari n g p ote ntial wit h a part ner ca p a ble of fat heri n g 
c hil dre n m ust be willi n g t o use 1 or m ore of t he f oll o wi n g f or ms of c o ntrace pti o n fr o m t he ti me of 
si g ni n g t he i nf or me d c o nse nt f or m f or t he d urati o n of t he st u d y:  
 H or m o nal c o ntrace pti o n ( oral, i m pla nta ble, i nject a ble, tra ns der mal)  
 Mec ha nic al c o ntrace pti o n (s per mici de i n c o nj u ncti o n wit h a barrier met h o d s uc h  as a 
c o n d o m or dia p hra g m)  
 I ntr a uteri ne d e vice 
 Vasect o miz e d part ner(s) ( 6 m o nt hs mi ni m u m)  
 W he n i n kee pi n g wit h a s u bject’s us ual lifest yl e a n d prefere nces, a bsti ne nce ma y als o be 
re gar de d as a n a de q uate met h o d of birt h c o ntr ol, w here a bsti ne n ce i n t his c o nte xt is defi ne d 
as refrai ni n g fr o m a n y s e x ual acti vities or c o ntact t hat ma y res ult i n creati o n of a z y g ote.  
o  N ote:  If a s u bj ect w h o was a bsti ne nt u n der t his defi niti o n bec o mes se x uall y acti ve 
d uri n g t he st u d y, t he y m ust a gree t o us e acce pt a ble c o ntrace pti o n as defi n e d a b o ve 
f or t he re m ai n der of t h e st u d y. 
Se x uall y acti ve male s u bjects wit h part ners w h o are W O C B P m ust be willi n g t o use 1 or m ore of 
t he a b o ve f or ms of birt h c o ntr ol f or eit her t he ms el ves or t heir part ner, as a p pr o priate, fr o m t he 
ti me of si g nin g t he i nf or me d c o nse nt f or m f or t he d urati o n of t he st u d y.  
 M ale s u bjects w h o u n der we nt a v asect o m y at least 6 m o nt hs bef ore V isit 1 ( Scree ni n g) are 
n ot re q uire d t o use a n y ot her f or ms of c o ntrace pti o n d uri n g t he st u d y. 
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 2  of 5 9  
1 2. 3  A p pe n di x 3: Slit L a m p Bi o micr o s c o py  
T he slit la m p bi o micr osc o p y e x a mi nati o n will b e perf or me d wit h t he slit la m p usi n g a bea m wi dt h 
a n d i nte nsit y t hat pr o vi d es o pti mal e val uati o n of t he a nteri or se g me nt. T he slit la m p bi o micr osc o p y 
e x a mi nati o n d oes n ot re q uire fl u ores cei n d ye, alt h o u g h  fl u orescei n d ye ma y be use d at I n vesti gat or 
discreti o n.  
T he slit la m p bi o micr os c o p y e x a mi nati o n m ust be perf or me d bef ore a n y pr oce d ures t hat w o ul d 
re q uire c o nt act wit h t he e ye a n d bef ore t he a p plicati o n of a n y dilati n g or a n est hetic e ye dr o ps. T he 
I n v estigat or s h o ul d use t heir sta n dar d e x a mi nati o n tec h ni q ue. T his pr oce d ure s h o ul d be perf or me d 
i n t he sa me ma n ner f or all s u bjects. W he n p ossi ble, t he sa me I n v esti gat or s h o ul d c o n d uct all slit 
la m p bi o micr osc o p y e x a mi nati o ns at eac h visit f or a gi v e n s u bject t hr o u g h o ut t he st u d y t o e ns ure 
c o nsiste nt gra di n g.  
T he I n vesti gat or m ust e xa mi ne eac h e ye (ri g ht e ye first, t he n left e ye) a n d rec or d a gra de f or eac h 
tiss ue/str uct ure liste d i n Ta ble 3 . O bser vati o ns s h o ul d be rec or de d i n t he s o urce d oc u me nt a n d 
l o g ge d i n t he a p pr o priat e e C R F. 
A ll s u bjects will u n der g o r o uti ne cataract s ur ger y a n d  i m pla ntati o n of a n i ntra oc ular l e ns; 
theref ore, all s u bjects will c ha n ge fr o m pha kic t o pse u d o p ha kic. T his s h o ul d n ot be c o nsi dere d a n 
A E, as it is a pla n ne d part of t he st u d y desi g n.  
T a ble 3  
Slit L a m p Tiss ue/ Str uct ure Assess me nts  
Tiss ue/ Str uct ure  
Gr a de  
E yeli ds & A d ne x a  
0 = N or mal; n o s welli n g/a b n or malit y of t he e yeli d tiss ue 
1 = A b n or mal  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, Cli nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _ 
C o nj u ncti v a  
C o nj u ncti v al H y pere mi a  
E de m a ( C he m osis)  
C o nj u ncti v al Disc h ar g e/ E x u d ate  
0 = N o ne  
1 = Mil d  
2 = M o derate  
3 = Se vere  
C or ne a  
C or ne al E de m a  
0 = N o ne  
1 = Mil d  
2 = M o derate  
3 = Se vere  
Iris 
0 = N or mal  
1 = A b n or mal  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, Cli nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _ 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 3  of 5 9  
Tiss ue/ Str uct ure  
Gr a de  
P u pil  
0 = N or mal  
1 = A b n or mal  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, Cli nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _ 
Scler a  
0 = N or mal; wit h o ut a n y re d ness/a b n or malit y  
1 = A b n or mal  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, Cli nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _  
Cr yst alli ne Le ns St at us  
P ha kic  
Pse u d o p ha kic  
A p ha kic  
T he se verit y of o c ular i nfla m mati o n will be assesse d b y t he In vesti gat or usi n g a slit la m p a n d 
gra de d usi n g t he  S U N W or ki n g Gr o u p Gra di n g Scale f or t he A nteri or C ha m ber ( Ta ble 4 ). 
T a ble 4  
S U N W or ki n g Gr o u p Gr a di n g Sc ale f or t he A nteri or C h a m ber  
A nteri or C h a m ber Cells  
 
A nteri or C h a m ber Fl are  
Gr a de  
Cells i n Fiel d 1 
Gr a de  
Descri pti o n  
0  
0  
0  
N o ne  
0. 5 +  
1 – 5  
1 +  
6 – 1 5  
1 +  
Fai nt  
2 +  
1 6 – 2 5  
2 +  
M o derate (iris a n d le ns details clear)  
3 +  
2 6 – 5 0  
3 +  
Mar ke d (iris a n d le ns details haz y)  
4 +  
> 5 0  
4 +  
I nte nse (fi bri n or plastic a q ue o us) 
A b bre viati o ns: S U N = Sta n dar dizati o n of U veitis N o me nclat ure  
1Fiel d size is a 1 m m b y 1 m m slit bea m 
Refere nce: J a bs et al., 2 0 0 5  
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 4  of 5 9  
1 2. 4  A p pe n di x 4: N u meric P ai n R ati n g Sc ale ( N P R S)  
S u bjects will be as ke d at eac h p ost -o p erati ve visit , e x cl u di n g Visit 7 ( Da y 2 1), t o rate t heir oc ular 
pai n i n t he st u d y e ye usi n g a n 1 1 -p oi nt N P R S scale. S u bjects will be pr o vi de d wit h pai n sc ore 
trai ni n g t o hel p har m o nize s u bjecti ve re p orti n g acr oss s u bjects a n d acr oss sites. 
“ 0” will re prese nt n o oc ular pai n. “ 1 0” will re pres e nt t he w o rst oc ular p ai n i ma gi na ble.  
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 5  of 5 9  
1 2. 5  A p pe n di x 5: Best C orrecte d Vis u al Ac uit y ( B C V A ) 
B C V A testi n g s h o ul d prece de a n y e x a mi nati o n re q uiri n g c o ntact wit h t he e ye a n d s h o ul d prece de 
p u pil dilati o n or i nstillati o n of a nest hetic e ye dr o ps. B C V A testi n g will  b e perf or me d f oll o wi n g 
ma nifest refracti o n . S u bjects will be teste d i n t heir ri g ht e ye first, f oll o we d b y t he left e ye.  
B C V A will be e val uate d i n eac h e ye i n di vi d uall y usi n g E T D R S c harts at a dista nce of 4 meters  
a n d sc ore d o n a Lo g M A R scale . BC V A s h o ul d  be e val u ate d c o nsiste ntl y t hr o u g h o ut t he st u d y 
usi n g t he sa me m et h o d, e q ui p me nt, a n d li g hti n g c o n diti o ns at eac h site .  
S u bjects will be i nstr uct e d t o r ea d t he letters o n t he E T D R S c hart fr o m the t o p left -h a n d c or ner 
al o n g eac h r o w, o n e letter at a ti me , t h e n d o w n eac h r o w, o n e at a ti me. T h ere are n o n u m bers o n 
t he c hart, o nl y letters. If a s u bject rea ds a n u m ber, t he e x a mi ner s h o ul d re mi n d t he s u bject t hat the 
c hart c o nt ai ns n o n u m bers , a n d t he e x a mi ner s h o ul d t he n re q u est a letter i nstea d of a n u m ber  fr o m 
t he s u bject. S u bjects s h o ul d be e nc o ura ge d t o g uess if a letter a p pears u n clear. If a s u bject i de ntifies 
a letter as 1 of 2 p ossi ble letters, t he e x a mi ner s h o ul d as k t he s u bject t o pic k 1 letter o nl y.  
S u bjects will be i nstr ucte d t o rea d sl o wl y at a r at e of a b o ut 1 letter  per s ec o n d. If at a n y p oi nt t he 
s u bject rea ds t o o q uic kl y, t he e x a mi ner s h o ul d st o p t he s u bject a n d re mi n d t he s u bject t o rea d 
sl o wl y i n or der t o ac hie v e t he best i de ntificati o n of eac h letter. If a s u bject l oses t heir place me nt 
i n t he c hart, t he e x a mi ner s h o ul d as k t he s u bject t o g o bac k t o t he li ne w here t h e place was l ost. 
T he s u bject s h o ul d n ot pr ocee d t o t he ne xt letter u ntil t he y ha ve gi ve n a defi nite res p o nse. If a 
s u bject c ha n ges a res p o nse bef ore m o vi n g o n t o t he ne xt letter, t he e x a mi ner m ust acce pt t he 
c ha n ge. T h e e x a mi ner s h o ul d circle eac h c orrect letter o n t he V A  w or ks heet a n d dra w a si n gle li ne 
t hr o u g h eac h i nc orrect letter. 
At t he e n d of t he t est, t h e e x a mi ner will c o u nt t h e n u m ber of letters i n c orrectl y i de ntifie d , u p t o 
a n d i ncl u di n g t he last li ne rea d , a n d will rec or d t he res ults o n t he s o urce d oc u me nt. A V A letter 
sc ore will be calc ulate d a n d rec or de d i n t he s o urce d oc u me nts a n d in t he e C R F . 
Eac h letter has a sc ore val ue of 0. 0 2 l o g u nits. Si nce t here are 5 letters pe r li ne, t he t otal sc ore f or 
a li ne o n t he L o g M A R c hart re pres e nts a c ha n ge of 0. 1 l o g u nits. T he f or m ula use d i n calc ulati n g 
t he sc ore is: 
C alc ul ati o n : L o g M A R V A = Baseli ne val ue + ( n X 0. 0 2)  
w here : 
B aseli ne val ue is t he L o g M A R  n u m ber of t he last li ne rea d (at least 1 letter rea d 
c orrectl y i n t his li ne), a n d  
 
“ n” is t he t otal n u m ber of letters misse d , u p t o a n d i ncl u di n g t he last li ne rea d, a n d 
 
“ 0.0 2” is t he val ue f or eac h letter  
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 6  of 5 9  
1 2. 6  A p pe n di x 6: I ntr a oc ul ar Press ure (I O P)  
Int ra oc ular press ur e meas ure me nts ( 1 meas ure m e nt per e ye) sh o ul d be c o n d ucte d after t he slit 
la m p e x a mi nati o n is c o m plete d a n d bef ore p u pil dilati o n. T his met h o d re q uires t he a d mi nistrati o n 
of pr o paracai ne 0. 5 % t o t he e ye bef ore testi n g . T h ere s h o ul d al wa ys be ≥3 0 mi n utes bet wee n t h e 
a d mi nistrati o n  of t o pical a nest hetic a n d I P.  
IO P m eas ur e me nts s h o ul d be perf or me d usi n g a G ol d ma n n a p pla nati o n t o n o meter, ha n d h el d 
c o ntact t o n o meter, o r p n e u mat o n o meter  acc or di n g t o t he I n vesti gat or’s st a n dar d pr oce d ure. T h e 
sa me met h o d of meas uri n g I O P s h o ul d be use d o n t he sa me s u bject at all visits. N o n -c o ntact a n d 
re b o u n d met h o ds of testi n g I O P are n ot per mitte d.  
Meas ure me nts s h o ul d be ta ke n wit h t he s u bject seate d. All press ures s h o ul d be rec or de d i n m m H g, 
a n d meas ur e me nts s h o ul d be rec or de d i n t he e C R F .  
 
 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 7  of 5 9  
1 2. 7  A p pe n di x 7: Dil ate d O p ht h al m osc o p y  
A  dilate d f u n d us e x a mi nati o n will be p erf or me d after t he a p plicati o n of dilati n g dr o ps ( 1 % 
tr o pica mi de) a n d u p o n t h e I n vesti gat or c o nfir mi n g wit h a pe n li g ht t hat b ot h e yes are f ull y dilate d 
after w aiti n g 2 0 mi n utes. If t he p u pils are still res p o nsi ve t o li g ht, a n a d diti o nal dr o p will  be a d de d 
t o eac h e ye, a n d t he I n vesti gat or will  wait t o pr ocee d u ntil t he p u pils n o  l o n ger res p o n d t o t he pe n 
li g ht. Si nce dilati n g dr o ps are bei n g a p plie d, t h e f u n d us e x a mi nati o n m ust be perf or me d after 
vis ual ac uit y, I O P, a n d slit la m p e x a mi nati o n.  
T he e val u ati o n will i ncl u de assess me nt of t he vitre o us, reti na, m ac ula, c h or oi d, o ptic n er ve, a n d 
o ptic ner ve c u p -t o-disc rati o. After t he pr oce d ure, t he I n v esti gat or  will d eter mi ne if fi n di n gs are 
wit hi n n or mal li mits or are a b n or mal. O nl y s hifts fr o m N or mal t o A b n or mal , Cli nicall y 
Si g nifica nt , or fr o m A b n or mal , Not Cli nicall y Si g nifica nt , to A b n or m al , Cli nicall y Si g nifica nt, 
w ill be rec or de d as A Es. 
Vitre o us  
N or mal:  A bse nce of a n y o pacit y  
A b n or mal:  Prese nce of o pacit y  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, C li nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _ 
Reti n a  
N or mal:  A bse nce of acti ve i nfla m mati o n or si g nifica nt str uct ural c ha n ges  
A b n or mal:  Prese nce of acti ve i nfla m mat or y si g ns or si g nific a nt str uct ural c ha n ges  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, C li nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _  
M ac ul a  
N or mal:  A bse nce of acti ve i nfla m mati o n or si g nifica nt str uct ural c ha n ges  
A b n or mal:  Prese nce of acti ve i nfla m mat or y si g ns or si g nific a nt str uct ural c ha n ges  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, C li nicall y Sig nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _  
C h or oi d  
N or mal:  A bse nce of acti ve i nfla m mati o n or si g nifica nt str uct ural c ha n ges  
A b n or mal:  Prese nce of acti ve i nfla m mat or y si g ns or si g nific a nt str uct ural c ha n ges  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal , C li nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _ 
O ptic Ner ve  
N or mal:  A bse nce of a n y da ma ge  
A b n or mal:  Prese nce of a n y da ma ge  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, C li nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _ 
C u p -t o-Disc  R ati o  
V ertical O ptic Ner ve C u p -t o-Disc Rati o: _ _. _ _ _ _  
H oriz o ntal O ptic Ner ve C u p -t o-Disc Rati o: _ _. _ _ _ _  
Ot her  
I n dic ate a n y ot her dil ate d f u n d us o p ht h al m osc o p y fi n di n gs:  
N or mal  
A b n or mal  
N ot Cli nicall y Si g nifica nt  
Cli nicall y Si g nifica nt  
If A b n or mal, C li nicall y Si g nifica nt, s pecif y: _ _ _ _ _ _ _ _ _ _ _ _ 

Vi va Visi o n Bi otec h ( H o n g K o n g) Lt d.  
 
Cli nical St u d y Pr ot oc ol: V V N 4 6 1 -C S -2 0 1  
 
 
V V N 4 6 1  O p ht hal mic S ol uti o n  
C O N FI D E N TI A L  
P r ot oc ol, v4 . 0, 1 3 Fe b 2 0 2 4  
 
P a ge 5 9  of 5 9  
1 2. 9  A p pe n di x 9 : I n vesti g at or A gree me nt 
A p h as e 2, d o u bl e -m as k e d, r a n d o mi z e d, v e hi cl e -c o nt r oll e d st u d y of 
V V N 4 6 1 O p ht h al mi c S ol uti o n i n t r e ati n g p ost -o p e r ati v e o c ul a r 
i nfl a m m ati o n i n s u bj e cts u n d e r g oi n g r o uti n e u nil at e r al c at a r a ct 
s u r g e r y 
V e rsi o n N u m b e r : 4 . 0 
Iss u e D at e: 1 3  F e b r u a r y 2 0 2 4  
I ha ve rea d t he cli nical st u d y pr ot oc ol a n d u n derst a n d it. I a gree t o c o n d uct t he st u d y as o utli ne d 
i n t his d oc u me nt a n d i n acc or da n ce wit h G C P, a ll l ocal a n d fe d eral re q uire me nts a n d re g ulati o ns, 
a n d i n c o m plia nce wit h t h ose pre ce pts set f ort h i n t he Declarati o n of Helsi n ki wit h res pect t o t he 
use of h u ma n s u bjects i n cli nical st u dies a n d i n vesti gati o ns.  
T he In vesti gat or  will a ss ure t hat n o de viati o n fr o m, or c ha n ges t o, t he pr ot oc ol will ta ke place 
wit h o ut a d va nce a gree m e nt fr o m t he  S p o ns or a n d d oc u me nte d a p pr o val f r o m t he I R B, ex ce pt 
w here necessar y t o eli mi nate a n i m me diate hazar d(s) t o su bject s. All pers o n nel i n v ol ve d i n t he 
c o n d uct of t he st u d y ha v e c o m plete d H u ma n S u bj ects Pr otecti o n a n d I C H G C P Trai ni n g.  
T he pr ot oc ol, i nf or me d c o nse nt f or m(s), recr uit me nt materials, a n d all s u bject materials will be 
s u b mitte d t o t he I R B i n a d va nce f or re vie w a n d a p pr o val. A p pr o val of b ot h t he pr ot oc ol a n d t h e 
i nf or me d c o nse nt f or m m ust be o btai ne d bef ore a n y s u bject is e nr olle d. A n y a m e n d me nt t o t he 
pr ot oc ol will re q uire re vie w a n d a p pr o val b y t h e I R B bef ore t he c h a n ges are i m ple me nte d t o t he 
st u d y. All c ha n ges t o t he c o nse nt f or m will be a p pr o ve d b y t he I R B ; a deter mi nati o n will be ma de 
re gar di n g w het her a n e w c o nse nt n ee ds t o b e o btai ne d fr o m s u bjects w h o pr o vi de d i nf or me d 
c o nse nt  u si n g a pre vi o usl y a p pr o ve d versi o n of t he c o nse nt f or m.  
F urt her, I a gree t o mai ntai n t he c o nfi de ntialit y of all i nf or mati o n recei ve d or de vel o pe d i n 
c o n necti o n wit h t his pr ot oc ol.  
 
Si g n at ure of I n vesti g at or:  
 
 
 
Na me ( pri nte d)  
Si g nat ure  
Date