A Multi-Center, Randomized, Parallel-Group, Phase 2, Masked, Three-Arm Trial to Compare Safety, Tolerability, Efficacy, and Durability of Two Dose Levels of Suprachoroidal Sustained-Release OXU-001 (Dexamethasone Microspheres; DEXAspheres®) Using the Oxulumis® Illuminated Microcatheterization Device Compared With Intravitreal Dexamethasone Implant (OZURDEX®) in Subjects With Diabetic Macular Edema (OXEYE)
Phase: PHASE2
Conditions: Diabetic Macular Edema
Sponsor: Oxular Limited

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1  of  1 6 9  
 
 
 
O x ular Li mite d  
Cli nical Trial Pr ot oc ol  
Cli nical Trial Pr ot oc ol Title:  
A  M ulti -C e nt er,  R a n d o mi z e d, P ar all el -Gr o u p, P h as e 2, M as k e d, T hr e e -Ar m Tri al  
t o C o m p ar e S af et y, T ol er a bilit y, Effi c a c y, a n d D ur a bilit y of T w o D os e L e v els of 
S u prac h or oi dal S ustai ne d -Release  O X U -0 0 1 ( D e x a m et h as o n e Mi cr o s p h er e s; 
D E X As p h er e s ® ) Usi n g t h e O x ul u mis ®  Ill u mi n at e d Mi cr o c at h et eri z ati o n D e vi c e 
C o m p ar e d wit h I ntr a vitr e al D e x a m et h as o n e I m pl a nt ( O Z U R D E X
® ) i n S u bj e cts 
wit h Di a b eti c M a c ul ar E d e m a  ( O X E Y E). 
S p o ns or Pr ot oc ol #  
O X U C T -1 0 2  
Cli nical Trials. g o v I de ntifier:  
N C T 0 5 6 9 7 8 0 9  
E U  C T I de ntifier N o.:  
2 0 2 3 -5 0 3 4 9 6 -1 7 -0 0  
I n vesti gati o nal Pr o d uct Na me: 
S u prac h or oi dal S ustai ne d -Release  O X U -0 0 1 
c o m pare d t o I ntra vitreal Oz ur de x ®  i n t he Treat me nt 
of Dia betic Mac ular E d e ma  
C T Versi o n:  
U S 4. 0  ( U S-s pecific v ersi o n) 
Date:  
2 7  Oct o ber  2 0 2 3  
S p o ns or:  
 
O x ular Lt d.  
Ma g dale n Ce ntre  
1 R o bert R o bi ns o n Ave n ue  
O xf or d  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2  of  1 6 9  
O X 4 4 G A, U nite d Ki n g d o m  
E mail: O X U C T -1 0 2 @ o x ular.c o m   
Tele p h o ne: + 4 4 ( 0) 1 8 6 5 6 3 6 2 0 0  
F u n di n g S o urce:  
O x ular Lt d.  
A ut h or(s):  
P D Dr. me d. Frie dric h As m us, M D,  
C hief Me dical Officer  
O x ular Lt d.  
C o ntact I nf or mati o n f or Me dical 
O versi g ht:  
 
O x ular Me dical M o nit or - Cli nical De vel o p me nt  
O x ular Li mite d, Ma g dale n Ce ntre, 1 R o bert 
R o bi ns o n A ve n ue O xf or d O X 4 4 G A, U nite d 
Ki n g d o m  
O X U C T -1 0 2 -u n mas k e d @ o x ular.c o m  
 
C o nfi de nti alit y St ate me nt  
T his d oc u me nt i ncl u des c o nfi de ntial a n d pri vile ge d i nf or mati o n a n d dat a t hat c o ntai n tra de 
secrets t hat are t he pr o pert y of O x ular Li mite d. T his i nf or mati o n s hall n ot be ma de p u blic 
wit h o ut pri or writte n per missi o n of O x ular Li mite d. T his d oc u me nt ma y be d iscl ose d t o a n d 
use d b y t he staff t h at c o n d ucts t he cli nical trial at a cli nical trial site, w h o are u n der a 
c o nfi de ntialit y a gree me nt wit h O x ular Li mite d a n d/ or t he C o ntract Researc h Or ga nizati o n 
c o n d ucti n g t his cli nical trial.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 3  of  1 6 9  
Si g n at ures  
I here b y c o nfir m t hat I a p pr o ve of t his cli nical tri al pr ot oc ol a n d a gree t o c o m pl y wit h its 
ter ms as lai d o ut i n t his d oc u me nt.  
S p o ns or si g nat or y:  
P D Dr. me d. Frie dric h As m us , M D, 
C hief Me dical Officer  
 
 
N a me, F u ncti o n ( pri nt)  
Si g n at ure  
D ate  
I here b y c o nfir m t hat I a p pr o ve of t his cli nical tri al pr ot oc ol a n d a gree t o c o m pl y wit h its 
ter ms as lai d o ut i n t his d oc u me nt.  
C o or di nati n g Pri nci pal I n vesti gat or:  
 
 
N a me:  
F u ncti o n:  
Or g a niz ati o n:  
A d dress:  
Tele p h o ne:  
Si g n at ure  
D ate  
I here b y c o nfir m t hat I a p pr o ve of t his cli nical tri al pr ot oc ol a n d a gree t o c o m pl y wit h its 
ter ms as lai d o ut i n t his d oc u me nt.  
Pri nci pal I n vesti gat or:  
 
 
N a me:  
F u ncti o n:  
Or g a niz ati o n:  
A d dress:  
Tele p h o ne:  
Si g n at ure  
D ate  
 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 4  of  1 6 9  
Ta ble of C o nte nts  
 
Ta ble of C o nte nts ........................................................................................................................ 4  
List of Fi g ures  ............................................................................................................................ 7  
List of Ta bles  .............................................................................................................................. 7  
List of A b bre viati o ns  .................................................................................................................. 9  
1  
Pr ot oc ol S u m mar y  ............................................................................................................. 1 2  
1. 1  
S y n o psis  ............................................................................................................................. 1 2  
1. 2  
St u d y Sc he matic  ................................................................................................................ 3 5  
1. 3  
Sc he d ule of Acti vities ....................................................................................................... 3 6  
2  
I ntr o d ucti o n ....................................................................................................................... 4 6  
2. 1  
St u d y Rati o nale  ................................................................................................................. 4 6  
2. 2  
Bac k gr o u n d  ........................................................................................................................ 4 7  
2. 3  
N o ncli nical e x perie nces wit h D M A micr os p heres i n t he s u prac h or oi dal 
s pace ................................................................................................................................... 5 0  
2. 4  
Be nefit/ Ris k Assess me nt  .................................................................................................. 5 1  
3  
O bjecti ves, E n d p oi nts, a n d Esti ma n ds  .............................................................................. 5 5  
3. 1  
O bjecti ves a n d E n d p oi nts  ................................................................................................ 5 5  
3. 2  
Esti ma n ds  ........................................................................................................................... 5 8  
4  
St u d y Desi g n  ..................................................................................................................... 5 8  
4. 1  
O verall Desi g n  .................................................................................................................. 5 8  
4. 1. 1  
Scie ntific Rati o nale f or t he St u d y Desi g n  ................................................................... 6 5  
4. 2  
J ustificati o n of D ose ......................................................................................................... 6 7  
4. 3  
E n d -of -St u d y Defi niti o n  .................................................................................................. 6 8  
5  
St u d y P o p ulati o n  ............................................................................................................... 6 8  
5. 1  
I ncl usi o n Criteria .............................................................................................................. 6 8  
5. 2  
E xcl usi o n Criteria  ............................................................................................................. 6 9  
6  
St u d y I nter ve nti o ns A d mi nistere d  ..................................................................................... 7 4  
6. 1  
O X U -0 0 1 –  D E X As p heres A d mi nistere d wit h t he O x ul u mis ®  .................................. 7 7  
6. 1. 1  
De xa met has o n e A cetat e Micr os p heres ( D E X As p h eres ® ) ........................................... 7 7  
6. 1. 2  
O x ul u mis ®  S u prac h or oi dal O p ht hal mic A d mi nistrati o n De vice  ................................. 7 7  
6. 1. 2. 1  
De vice Ma n ufact uri n g Pr ocess  ....................................................................................... 7 8  
6. 1. 2. 2  
I nte n de d Perf or ma nce a n d C o ntrai n dicati o ns ............................................................... 7 8  
6. 1. 2. 3  
De vice D escri pti o n  ........................................................................................................... 7 9  
6. 1. 2. 4  
I nstr ucti o ns f or I nstallati o n a n d Use .............................................................................. 8 1  
6. 1. 2. 5  
S u m mar y of Necessar y Trai ni n g a n d E x peri e nce ......................................................... 8 1  
6. 1. 2. 6  
O x ul u mis ®  Acc o u nta bilit y  ............................................................................................... 8 1  
6. 2  
Oz ur de x ®  ............................................................................................................................ 8 2  
6. 3  
Lifest yle C o nsi derati o ns  .................................................................................................. 8 2  
6. 4  
Scree n Fail ures  .................................................................................................................. 8 2  
7  
St u d y I nter ve nti o n(s) a n d C o nc o mita nt T hera pies  ........................................................... 8 3  
7. 1  
Dr u g Pre parati o n, Ha n dli n g St ora ge, a n d Acc o u nt a bilit y  ........................................... 8 3  
7. 1. 1  
O X U -0 0 1  ..................................................................................................................... 8 3  
7. 1. 1. 1  
Pac ka gi n g a n d La b eli n g  ................................................................................................... 8 3  
7. 1. 1. 2  
St ora ge  ................................................................................................................................ 8 4  
7. 1. 1. 3  
Pre parati o n  ......................................................................................................................... 8 4  
7. 1. 1. 4  
A d mi nistrati o n  ................................................................................................................... 8 4  
7. 1. 2  
Oz ur de x ®  ..................................................................................................................... 8 5  
7. 2  
Assi g n me nt t o St u d y I nter ve nti o n  .................................................................................. 8 5  
7. 2. 1  
Part A  ........................................................................................................................... 8 5  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 5  of  1 6 9  
7. 2. 2  
Part B  ........................................................................................................................... 8 5  
7. 3  
Mas ki n g  .............................................................................................................................. 8 6  
7. 4  
St u d y I nter ve nti o n C o m plia nce  ...................................................................................... 8 9  
7. 5  
D ose M o dificati o n, F oll o w -o n Treat me nt, a n d Treat me nt of Dia betic 
Reti n o pat h y C o m plicati o ns  ............................................................................................. 9 0  
7. 5. 1  
D ose Le vel C o nfir mati o n i n Part B Treat me nt Ar m B 2  .............................................. 9 0  
7. 5. 2  
F oll o w -o n Treat me nt  ................................................................................................... 9 0  
7. 5. 3  
Treat me nt of Dia b etic Reti n o pat h y Pr o gressi o n a n d C o m plicati o ns  .......................... 9 1  
7. 6  
C o nti n ue d Access t o St u d y I nter ve nti o n aft er t he E n d of t he St u d y  .......................... 9 2  
7. 7  
Treat me nt of O ver d ose  ..................................................................................................... 9 2  
7. 8  
Pri or a n d C o nc o mita nt T hera p y  ...................................................................................... 9 2  
7. 8. 1  
Pr o hi bite d Me dicati o ns a n d/ or Treat me nts  .................................................................. 9 3  
7. 8. 2  
C o nc o mita nt Me dicati o ns  ............................................................................................ 9 7  
7. 9  
Criteria f or Te m p oraril y Dela yi n g Part(s) of t he St u d y  ............................................... 9 7  
7. 9. 1  
C O VI D -1 9 Relate d Preca uti o ns  .................................................................................. 9 7  
8  
Disc o nti n uati o n of St u d y I nter ve nti o n a n d S u bject Dis p ositi o n 
Disc o nti n uati o n/ Wit h dra wal  ............................................................................................ 9 8  
8. 1  
Disc o nti n uati o n of St u d y I nter ve nti o n  ........................................................................... 9 8  
8. 2  
S u bject Disc o nti n uati o n/ Wit h dra wal fr o m t he St u d y  ................................................. 9 8  
8. 3  
L ost t o F oll o w -U p ............................................................................................................. 9 9  
9  
St u d y Assess me nts a n d Pr oce d ures  ................................................................................. 1 0 0  
9. 1  
E val uati o ns Perf or me d D uri n g I n vesti gati o nal Visits  ................................................ 1 0 1  
9. 1. 1  
Baseli ne Visit V 2 A cti vities  ....................................................................................... 1 0 1  
9. 1. 2  
O pti o nal Safet y Visit Wee k 6 –  Part B  ...................................................................... 1 0 2  
9. 1. 3  
Earl y Ter mi nati o n Visit .............................................................................................. 1 0 2  
9. 1. 4  
U nsc he d ule d Visit  ...................................................................................................... 1 0 3  
9. 2  
A d mi nistrati ve a n d Ge neral/ Baseli ne Pr oce d ures  ...................................................... 1 0 3  
9. 2. 1  
C o nse nt F or m C o m pleti o n  ........................................................................................ 1 0 3  
9. 2. 2  
De m o gra p hic I nf or mati o n a n d Me dical Hist or y  ....................................................... 1 0 3  
9. 2. 3  
Eli gi bilit y Assess me nt  ............................................................................................... 1 0 3  
9. 2. 4  
Assess me nt of E x pect e d Pr oce d ural C o m ple xit y  ...................................................... 1 0 4  
9. 2. 5  
Pre g na nc y Test  ........................................................................................................... 1 0 4  
9. 2. 6  
A d verse E v e nt a n d A d verse De vice Effect C ollecti o n  .............................................. 1 0 4  
9. 2. 7  
C o nc o mita nt Me dicati o n Re vie w  .............................................................................. 1 0 4  
9. 2. 8  
P har mac o ki netic Bl o o d Sa m pli n g  ............................................................................. 1 0 5  
9. 2. 9  
St u d y I nter ve nti o n  ..................................................................................................... 1 0 5  
9. 2. 1 0  N EI V F Q -2 5  .............................................................................................................. 1 0 5  
9. 2. 1 1  D oc u me ntati o n a n d Assess me nt of t he A d mi nistrati o n Pr oce d ure ............................ 1 0 5  
9. 2. 1 2  Patie nt E x perie nce Assess me nt  ................................................................................. 1 0 6  
9. 2. 1 3  Dis p ositi o n of Sa m ples  .............................................................................................. 1 0 6  
9. 3  
Oc ular Assess me nts  ........................................................................................................ 1 0 6  
9. 3. 1  
A xial Le n gt h Meas ur e me nt  ....................................................................................... 1 0 6  
9. 3. 2  
I O P Meas ur e me nt ...................................................................................................... 1 0 7  
9. 3. 3  
Slit -La m p Bi o micr osc o p y  ......................................................................................... 1 0 7  
9. 3. 4  
Dilate d I n direct O p ht hal m osc o p y .............................................................................. 1 0 8  
9. 3. 5  
Best -C orrecte d Vis ual A c uit y  .................................................................................... 1 0 8  
9. 3. 6  
S pectral -D o mai n O ptical C o here nce To m o gra p h y  .................................................... 1 0 9  
9. 3. 7  
Peri p heral S we pt -S o urce O C T or Peri p heral E n ha n ce d De pt h I m a gi n g 
( E DI) O C T ............................................................................................................. 1 0 9  
9. 3. 8  
A nteri or Se g me nt O C T (i n Part A o nl y)  .................................................................... 1 1 0  
9. 3. 9  
C ol or F u n d us P h ot o gra p h y  ........................................................................................ 1 1 0  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 6  of  1 6 9  
9. 3. 1 0  Fl u orescei n A n gi o gra p h y ........................................................................................... 1 1 0  
9. 4  
Safet y Assess me nts  .......................................................................................................... 1 1 1  
9. 4. 1  
A d verse E v e nt a n d A d verse De vice Effect C ollecti o n  .............................................. 1 1 1  
9. 4. 2  
La b orat or y Testi n g  ..................................................................................................... 1 1 1  
9. 4. 3  
Vital Si g ns, Wei g ht, a n d Hei g ht  ................................................................................ 1 1 2  
9. 5  
Safet y Re p orti n g of A d v erse E ve nts a n d Seri o us A d verse E v e nts  ............................1 1 2  
9. 5. 1  
Ti me Peri o d a n d Fre q ue n c y of Safet y I nf or mati o n  ................................................... 1 1 3  
9. 5. 2  
Met h o d of Dete cti n g Safet y E ve nts  ........................................................................... 1 1 4  
9. 5. 3  
F oll o w -u p of Safet y E ve nts  ....................................................................................... 1 1 4  
9. 5. 4  
Re g ulat or y Re p orti n g Re q uire me nts of Seri o us Safet y E ve nts  ................................. 1 1 4  
9. 5. 5  
C o ntrace pti o n G ui da nce  ............................................................................................ 1 1 5  
9. 5. 6  
A d verse E v e nts of S peci al I nterest  ............................................................................ 1 1 6  
9. 5. 7  
Pre g na nc y  .................................................................................................................. 1 1 7  
9. 5. 8  
Disease -Rel ate d E ve nts a n d/ or O utc o mes n ot Q ualif yi n g as Safet y E ve nts  ............. 1 1 8  
9. 5. 9  
Me dical De vic e Deficie n cies  ..................................................................................... 1 1 8  
9. 6  
P har mac o ki netics  .............................................................................................................1 1 9  
1 0  Statistical C o nsi derati o ns  ................................................................................................ 1 2 0  
1 0. 1  
Statistical H y p ot hesis  ..................................................................................................... 1 2 0  
1 0. 2  
Sa m ple Size Deter mi nati o n  ........................................................................................... 1 2 0  
1 0. 3  
A nal ysis Sets  ................................................................................................................... 1 2 2  
1 0. 3. 1  F ull A nal ysis Set  ........................................................................................................ 1 2 2  
1 0. 3. 2  Per Pr ot oc ol Set  ......................................................................................................... 1 2 2  
1 0. 3. 3  Safet y  A n al ysis Set  .................................................................................................... 1 2 2  
1 0. 3. 4  P har mac o ki netics ( P K)  A nal ysis Set  ......................................................................... 1 2 3  
1 0. 4  
Statistical A nal yses  ......................................................................................................... 1 2 3  
1 0. 4. 1  Ge neral C o nsi derati o ns  ............................................................................................. 1 2 3  
1 0. 4. 2  Safet y A n al ysis  .......................................................................................................... 1 2 3  
1 0. 4. 3  E x pl orat or y Efficac y a n d Safet y A nal yses  ................................................................ 1 2 4  
1 0. 4. 4  P har mac o ki netics A nal ys es  ....................................................................................... 1 2 5  
1 0. 4. 5  I m p orta nt Pr ot oc ol Vi olati o ns ................................................................................... 1 2 5  
1 0. 4. 6  Ot her A n al yses ........................................................................................................... 1 2 6  
1 0. 4. 6. 1  S u bject Dis p ositi o n a n d Baseli ne C haracteristics  ...................................................... 1 2 6  
1 0. 4. 6. 2  Me dical Hist or y ............................................................................................................... 1 2 6  
1 0. 4. 6. 3  Ot her Safet y  ..................................................................................................................... 1 2 6  
1 0. 4. 6. 4  C o nc o mita nt Me dicati o ns  .............................................................................................. 1 2 6  
1 0. 4. 6. 5  P h ysicia n Pr oce d ure Ass ess me nt  .................................................................................. 1 2 6  
1 0. 4. 6. 6  Patie nt E x perie nce Assess me nt  ..................................................................................... 1 2 6  
1 0. 4. 7  Missi n g Data a n d I m p utati o n Met h o ds  ..................................................................... 1 2 6  
1 1  S u p p orti n g D oc u me ntati o n a n d O perati o nal C o nsi derati o ns  .......................................... 1 2 7  
1 1. 1  
Re g ulat or y, Et hical, A n d St u d y O versi g ht C o nsi derati o ns  ....................................... 1 2 7  
1 1. 1. 1  Re g ulat or y a n d Et hical C o nsi derati o ns  ..................................................................... 1 2 7  
1 1. 1. 2  Fi na ncial Discl os ure  .................................................................................................. 1 2 8  
1 1. 1. 3  I nf or me d C o nse nt Pr ocess ......................................................................................... 1 2 8  
1 1. 1. 4  Recr uit me nt Strate g y  ................................................................................................. 1 2 9  
1 1. 1. 5  Data Pr otecti o n  .......................................................................................................... 1 2 9  
1 1. 1. 5. 1  Or ga niz ati o nal a n d Tec h nical Arra n ge m e nts  .............................................................. 1 2 9  
1 1. 1. 5. 2  C o nfi de ntialit y Meas ures  ............................................................................................... 1 3 0  
1 1. 1. 5. 3  Miti gati o n Meas ures i n Case of Data S ec urit y Breac h  .............................................. 1 3 0  
1 1. 1. 6  C o m mittees Str uct ure  ................................................................................................ 1 3 1  
1 1. 1. 6. 1  Data M o nit ori n g C o m mittee  ......................................................................................... 1 3 1  
1 1. 1. 6. 2  St u d y Steeri n g C o m mittee  ............................................................................................. 1 3 1  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 7  of  1 6 9  
1 1. 1. 7  Disse mi nati o n of Cli nical St u d y Data  ....................................................................... 1 3 1  
1 1. 1. 8  Data Q ualit y Ass ura nce  ............................................................................................. 1 3 2  
1 1. 1. 9  S o urce D oc u m e nts  ..................................................................................................... 1 3 3  
1 1. 1. 1 0  St u d y a n d Site Start a n d Cl os ure  ............................................................................... 1 3 4  
1 1. 1. 1 1  P u blicati o n P olic y  ...................................................................................................... 1 3 5  
1 1. 2  
Safet y: E ve nts, Defi niti o ns, a n d Pr oce d ures  ............................................................... 1 3 5  
1 1. 2. 1  E mer ge n c y C o ntacts f or I n vesti gat or Re p orti n g of Safet y E ve nts  ............................ 1 3 5  
1 1. 2. 2  A d verse E v e nts Defi niti o n  ........................................................................................ 1 3 6  
1 1. 2. 3  De vice A d verse E ve nts a n d De vice A d verse Effects Defi niti o ns  ............................. 1 3 6  
1 1. 2. 4  Ti me Peri o d f or Detecti n g De vice Deficie ncies  ........................................................ 1 3 7  
1 1. 2. 5  F oll o w -u p Peri o d of De vice Defi cie ncies  ................................................................. 1 3 7  
1 1. 2. 6  Re p orti n g Re q uire me nts of De vice Defi cie ncies  ...................................................... 1 3 7  
1 1. 2. 7  Re g ulat or y Re p orti n g Re q uire me nts ( Seri o us Safet y E ve nts, Safet y 
Re p orti n g i n Cli nical I n vesti gati o ns of Me dical D e vices, a n d D S U R).  ................ 1 3 8  
1 1. 2. 8  Seri o us A d vers e E ve nt D efi niti o n  ............................................................................. 1 3 9  
1 1. 2. 9  S us pecte d U ne x p ecte d S eri o us A d verse Reacti o n Defi niti o n  ................................... 1 4 0  
1 1. 2. 1 0  De vice Seri o us A d verse E ve nt, Seri o us A d verse De vice Effect, a n d 
U ne x pect e d Seri o us A d v erse De vice Effect Defi niti o ns  ....................................... 1 4 1  
1 1. 2. 1 1  Rec or di n g a n d F oll o w -U p of A d verse E v e nts a n d/ or Seri o us A d verse 
E ve nts ( Dr u g or De vic e)  ........................................................................................ 1 4 2  
1 2  O utc o me Ass ess me nts a n d Q uesti o n naires  ..................................................................... 1 4 8  
1 2. 1  
S u bject’s E x perie nce Ass ess me nt –  Visit 2, Da y 0 ..................................................... 1 4 8  
I nstr ucti o ns f or t he site i nter vie wer: ....................................................................................... 1 4 8  
I nstr ucti o ns f or t he s u bject (t o be rea d t o t he s u bject b y t he i nter vie wer): ............................ 1 4 8  
1 2. 2  
S u bject’s E x perie nce Ass ess me nt –  Da y 1, Visit 3 t hr o u g h Wee k 4, Visit 
5  ......................................................................................................................................... 1 5 1  
I nstr ucti o ns f or site i nter vie wer: ............................................................................................ 1 5 1  
I nstr ucti o ns f or st u d y s u bject (t o be rea d t o t he s u bject b y t he i nter vie wer): ........................ 1 5 1  
1 2. 3  
Reti nal P h ysicia n’s Assess me nt of t he A d mi nistrati o n Pr oce d ure  ........................... 1 5 3  
1 2. 4  
G ui da nce o n Fact ors t o C o nsi der f or Assess me nt of E x pecte d Pr o ce d ural 
C o m ple xit y  ...................................................................................................................... 1 6 4  
1 3  Refere n ces  ....................................................................................................................... 1 6 8  
 
List of Fi g ures  
Fi g ure 1  St u d y O ver vie w Part A  ............................................................................................ 3 5  
Fi g ure 2 St u d y O ver vie w Part B  .............................................................................................. 3 5  
Fi g ure 3 Ill ustrati o n of t he O x ul u mis ® S u prac h or oi dal Micr ocat het erizati o n De vice  ............ 8 0  
Fi g ure 4 Sc he matic Dra wi n g of t he O x ul u mis S u prac h or oi d al Micr ocat het erizati o n De vi ce  . 8 0  
List of Ta bles  
Ta ble 1 Part A Sc he d ul e of Acti vities  ....................................................................................... 3 6  
Ta ble 2 Part B Sc he d ule of Acti vities  ....................................................................................... 3 9  
Ta ble 3 Part A  Baseli ne Visit V 2 - Alter n ati ves Sc he d uli n g O pti o ns  ...................................... 4 2  
Ta ble 4 Part B Alter n ati ves Sc he d uli n g O pti o ns f or Baseli ne Visit Acti vities  ......................... 4 4  
Ta ble 5 O bjecti ves a n d E n d p oi nts  ............................................................................................ 5 5  
Ta ble 6 Part A Treat me nt Ar ms, I nter ve nti o ns, a n d N u m ber of S u bjects  ................................ 5 9  
Ta ble 7 Part B Treat me nt Ar ms, I nter ve nti o ns, a n d N u m ber of S u bjects  ................................ 5 9  
Ta ble 8 St u d y I nter ve nti o n(s) A d mi nistere d i n Part A a n d Part B  ............................................ 7 4  

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Ta ble 9 Treat me nt Ar ms i n Part A  ............................................................................................ 7 6  
Ta ble 1 0 Treat me nt Ar ms i n Part B  .......................................................................................... 7 6  
Ta ble 1 1 Pr o hi bite d Me di cati o ns a n d/ or Treat me nts  ................................................................ 9 4  
Ta ble 1 2 Pr o ba bilit y of f oll o w -o n treat me nt b y Wee k 2 4 f or Oz ur de x ®  ................................ 1 2 1  
Ta ble 1 3 Pr o ba bilit y of A d verse Safet y E ve nt f or Oz ur de x ®  ................................................. 1 2 2  
 

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List o f A b bre vi ati o ns 
4 W F  
F o ur Wi de -Fiel d F u n d us P h ot o gra p h y  
A D E  
A d verse D e vice Effect  
A E  
A d verse E v e nt  
A E SI  
A d verse E v e nt o f S pecial I nterest 
A nti -V E G F  
A nti -Vasc ular Gr o wt h Fact or  
A M D  
A ge Relate d Mac ular De ge nerati o n  
A S -O C T  
A nteri or Se g me nt –  O pti cal C o here n ce To m o gra p h y  
A U C  
Area U n der t he C ur ve  
B C V A  
Best C orrecte d Vis u al Ac uit y  
B R V O  
Bra nc h Reti nal Vei n O ccl usi o n  
B M  
Bi o micr osc o p y  
C E P  
Cli nical E val uati o n Pla n  
C F P  
C ol or F u n d us P h ot o gra p h y  
C ma x  
Ma xi mal C o nce ntrati o n  
C M O  
C o ntract Ma n ufact uri n g Or ga nizati o n  
C o njI ncisi o n  
C o nj u ncti va I ncisi o n  
C R C  
Ce ntral Rea di n g Ce nter  
C R F  
Case Re p ort F or m  
C R V O  
Ce ntral Reti nal Vei n Occl usi o n  
C S T  
Ce ntral S u bfiel d T hic k ness  
D M A  
De xa met has o n e A cetat e  
D M C  
Data M o nit ori n g C o m mittee  
D M E  
Dia betic Mac ul ar E de m a  
D R  
Dia betic Reti n o pat h y  
D X M  
De xa met has o n e  
E DI -O C T  
E n ha nce d D e pt h I ma gi n g O ptical C o here n ce To m o gra p h y  
E M A  
E ur o pea n Me dici nes A ge nc y  
E o S  
E n d of St u d y  
E T D R S  
Earl y Treat me nt Di a betic Reti n o pat h y St u d y  
F A  
Fl u orescei n A n gi o gra p h y  
F A S  
F ull A nal ysis Set  
G C P  
G o o d Cli nical Practice  

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H b A 1c  
He m o gl o bi n A 1c  
I B 
I n vesti gat or Br oc h ure 
I C F 
I nf or me d C o nse nt F or m 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I E C 
I n de pe n de nt Et hics C o m mittee 
I F U 
I nstr ucti o ns f or Use 
I M P 
I n vesti gati o nal Me dici nal Pr o d uct 
I O P 
I ntra oc ular Press ur e 
I R 
( Near) I nfrare d I ma gi n g 
I R B 
I nstit uti o nal/I n de pe n de nt Re vie w B oar d 
I U D 
I ntra uteri ne De vic e 
I U S 
I ntra uteri ne S yste m 
I V R S 
I nteracti ve Voic e Res p o nse S yste m 
I V T 
I ntra vitreal 
I W R S 
I nteracti ve We b R es p o nse S yste m 
L A R  
Le gall y A ut h oriz e d Re prese ntati ve  
L L O Q  
L o wer Li mit of Q ua ntitati 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 ulat or y Acti vities  
M E  
Mac ular E d e ma  
N EI V F Q -2 5  
Nati o nal E ye I nstit ute Vis ual F u ncti o n Q uesti o n naire -2 5  
O U  
Oc ul us Uter q ue –  B ot h E yes  
P D R  
Pr oliferati ve Dia b etic Reti n o pat h y  
P D  
P har mac o d y na mic s 
PI  
Pri nci pal I n vesti gat or  
P K  
P har mac o ki netics  
P P S  
Per Pr ot oc ol Set  
P R N  
Pr o Re Nata (as nee d e d)  
P R P  
Pa nreti nal P h ot oc oa g ulati o n  
Q C  
Q ualit y C hec k  
R SI  
Refere n ce Safet y I nf or mati o n  
S A E  
Seri o us A d vers e E ve nt  
S A D E  
Seri o us A d vers e De vi ce Effect  
S A S  
Safet y A n al ysis Set  

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S A P  
Statistical A nal ysis Pla n  
S D  
Sta n dar d De viati o n  
S D -O C T  
S pectral D o mai n O ptical C o here nce To m o gra p h y  
S E  
St u d y E ye  
S o A  
Sc he d ule of Assess me nts  
S S C  
St u d y Steeri n g C o m mittee  
S S -O C T  
S we pt -S o urce O ptic al C o here nce To m o gr a p h y  
S U S A R  
S us pecte d U ne x p ecte d S eri o us A d verse Reacti o n  
T A  
Tria mci n ol o ne Acet o ni de  
T E A E  
Treat me nt -E mer g e nt N o n -Seri o us A d verse Effect  
T E D A E  
Treat me nt E mer g e nt N o n -Seri o us De vice A d verse Effect  
T ma x  
Ti me t o ma xi mal c o nce ntrati o n  
U P T  
Uri ne Pre g na n c y Test  
U S A D E  
U na ntici pate d Seri o us A d verse De vice Effect  
U S F D A  
U nite d States F o o d a n d Dr u g A d mi nistrati o n  
U W F  
Ultra -Wi de Fiel d   
V E G F  
Vasc ular E n d ot h elial Gr o wt h Fact or  
W FI  
Water f or I njecti o n  
 

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1  
Pr ot oc ol S u m m ar y  
1. 1  
S y n o psis  
Title  
A M ulti -C e nt er, R a n d o mi z e d, P ar all el -Gr o u p, P h as e 2, 
M as k e d, T hr e e -Ar m Tri al t o C o m p ar e S af et y, T ol er a bilit y, 
Effi c a c y, a n d D ur a bilit y of T w o D os e L e v els of 
S u pr a c h or oi d al S ust ai n e d -R el e as e O X U -0 0 1 
( D e x a m et h as o n e Mi cr os p h er es; D E X As p h er es ®) Usi n g t h e 
O x ul u mi s ® Ill u mi n at e d Mi cr o c at h et eri z ati o n D e vi c e 
C o m p ar e d wit h I ntr a vitr e al D e x a m et h as o n e I m pl a nt 
( O Z U R D E X ®) i n S u bj e ct s wit h Di a b eti c M a c ul ar E d e m a 
( O X E Y E). 
S p o ns or  
Pr ot oc ol #:  
O X U C T -1 0 2  
Cli nic al Tri als. g o v 
I de ntifier: 
N C T 0 5 6 9 7 8 0 9  
E U C T I de ntifier 
N o.:  
2 0 2 3 -5 0 3 4 9 6 -1 7 -0 0  
P h ase:  
P hase 2  
Brief Title  
S u prac h or oi dal S ustai ne d -Release O X U -0 0 1 c o m pare d t o I ntra vitreal 
Oz ur de x ®  i n t he Treat me nt of Dia betic Mac ular E de ma 
R ati o n ale  
T here is a great u n met n ee d f or Dia b etic Mac ul ar E de ma (D M E ) 
t hera pies, w hic h ha ve c o m pare d t o sta n dar d-of -care a nti -V E G F 
t hera pies a br oa der s pectr u m of p har mac ol o gical acti vities a n d 
t here b y als o a d dress t he str o n g i nfla m mat or y c o m p o ne nt of D M E. I n 
a d diti o n, t hera pies wit h a l o n g d urati o n of acti o n of m ore t ha n 
6  m o nt hs w o ul d re d uce t he treat me nt b ur d e n of patie nts. Oc ular 
c ortic oster oi ds ha v e t he p ote ntial t o a d dress t his u n met nee d, as t he y 
ha ve n ot o nl y s h o w n str o n g a nti -e de ma effects si milar t o a nti -V E G F 
treat me nts, b ut als o a br oa d a nti-i nfla m mat or y effect. Pr o gressi ve, 
c o nti n ue d reti nal a n d c h or oi dal i nfla m mati o n is a ke y dri ver of t h e 
pr o gressi o n of dia betic e ye disease.  

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Pr o vi de d a n acce pta ble s afet y pr ofile, o c ular ster oi ds ca n deli ver 
vis ual be nefit s i n D M E patie nts  t hat are tr eat me nt-naï ve as well as i n 
t h ose w h o s h o w e d li mite d, s h ort-li ve d, or n o vis ual i m pr o ve me nt wit h 
i ntra vitreal (I V T) a d mi nistere d a nti -V E G F dr u gs.  
T he use of c urre nt ster oi d t hera pies f or D M E, i ncl u di n g I V T 
Oz ur de x ® , is li mite d b y t he t y pical a n d fre q ue nt a d verse reacti o ns; 
s pecificall y, cataract f or mati o n a n d i ncreas e d i ntra oc ular press ure 
(I O P), w hic h us uall y re q uire a d mi nistrati o n of a d diti o nal o p ht hal mic 
dr u gs, e. g., I O P l o weri n g e ye dr o ps, gla uc o ma s ur ger y , or le ns 
re place me nt s ur ger y. D u e t o t hese safet y c o ncer ns a n d t he li mite d 
d ura bilit y of o nl y 3 -6 m o nt hs f or t he m ost fre q ue ntl y use d I V T ster oi d 
i m pla nt, t he c urre nt be nefit-ris k pr ofile of I VT ster oi ds i n D M E 
patie nts is s u b o pti mal.  
Acc or di n gl y, t here re m ai ns a hi g h u n met me dical nee d f or effi caci o us 
oc ular treat me nts f or dia betic mac ular e de ma ( D M E) wit h a m ore 
fa v ora bl e be nefit-ris k pr ofile. 
O X U -0 0 1 is a c o m bi nati o n s ustai ne d -release f or m ulati o n of 
de xa met has o ne acetate ( D M A) micr os p heres ( D E X As p heres ® ) 
a d mi nistere d s u prac h or oi dall y wit h t he O x ul u mis ®  o p ht hal mic 
ill u mi nate d micr ocat heterizati o n de vice  (a n o p ht h al mic a d mi nistrati o n 
de vice) . T h e tar g ete d d ura bilit y of O X U-0 0 1 bas e d o n precli nical 
e x peri me nts is u p t o 1 2  m o nt hs.  
O X U -0 0 1 has t he p ot e ntial f or l o n ger d ura bilit y beca use of t he 
c o m bi nati o n of a s ustai ne d -rel ease dr u g f or m ulati o n pl us a si m ple a n d 
r o uti ne deli ver y t o t he s u prac h or oi d al s pace. O X U-0 0 1 is e x pecte d t o 
ha ve a s ustai ne d a nti -e de ma effect a n d a re d u ce d i nci de nce of ster oi d -
relate d oc ul ar a d v erse e v e nts ( A Es). 
T he c urre nt trial has t he o bjecti ve of ge n erati n g  cli nical data t o assess 
t he f oll o wi n g as pects of s u prac h or oi d al O X U-0 0 1 i n D M E:  

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2.  T o e x pl ore t he efficac y of 
s u prac h or oi dal O X U-0 0 1 
deter mi ne d b y c h a n ge i n 
vis ual ac uit y, e de ma c o ntr ol, 
a n d i m pact o n visi o n -relate d 
q ualit y of life i n s u bjects wit h 
D M E  
2.  Mea n C ha n ge B C V A ( E T D R S) 
at Wee k 2 4 c o m pare d t o 
baseli ne.  
3.  Mea n C ha n ge i n ce ntral 
s u bfiel d t hic k ness at Wee k 2 4 
c o m pare d t o bas eli ne.  
4.  Mea n C ha n ge B C V A ( E T D R S) 
t hr o u g h 
Wee k 5 2 c o m p are d t o 
baseli ne.  
5.  Mea n C ha n ge i n ce ntral s u bfiel d 
t hic k ness t hr o u g h 
Wee k 5 2 
c o m pare d t o bas eli ne.  
6.  
Mea n c ha n g e i n N EI V F Q -2 5 
T otal Sc ore at 
Wee k 2 4, a n d 
Wee k  5 2 c o m pare d t o b aseli ne.  
P h ar m ac o -
ki netics ( P K)  
Assess s yste mic e x p os ure of 
de xa met has o ne after 
a d mi nistrati o n of O X U -0 0 1.  
1.  De xa met has o n e le vels i n plas ma 
will be meas ure d at sc he d ule d 
ti me p oi nts  
( pre-d ose,  
a n d 
p ost -d ose 
at 
6 0 mi n, 
1  da y, 
1  wee k, 4  wee ks, 2 4 wee ks, a n d 
5 2  wee ks after a d mi nistrati o n of 
O X U -0 0 1 ). 
T he f oll o wi n g P K p ara m eters will b e 
e val uate d:  
1.  Ti me t o ma xi mal c o nce ntrati o n 
( T ma x) 
2.  Ma xi mal c o nce ntr ati o n ( C ma x)  
3.  Area u n d er t he c ur ve ( A U C)  

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visits fr o m Wee k 1 2 t hr o u g h 
Wee k 5 2.  
7.  Pr o p orti o n of s u bjects wit h 5 -, 
1 0 -, or 1 5-letter ( E T D R S) gai n 
of B C V A fr o m wee k 4 t o wee k 
5 2 c o m pare d t o bas eli ne.  
8.  Pr o p orti o n of s u bjects wit h 5 -, 
1 0 -, or 1 5-letter ( E T D R S) l oss 
of B C V A fr o m wee k 4 t o wee k 
5 2 c o m pare d t o bas eli ne.  
9.  Pr o p orti o n of s u bjects wit h 
B C V A  > 6 8  letters ( E T D R S) at 
eac h st u d y visit fr o m wee k 4 t o 
wee k 5 2.  
1 0.  Mea n c ha n g e i n N EI V F Q -2 5 
T otal Sc ore Wee k 2 4, a n d 
Wee k  5 2 c o m pare d t o b aseli ne.  
O ver all Desi g n  T his is a fift y -t w o-wee k ( 5 2 -wee k) trial wit h t w o parts . T he t otal ti me of 
trial partici pati o n ca n b e u p t o 58  wee ks, if t he ma xi m u m ti me i nter val 
f or perf or mi n g acti vities of t he B aseli ne V isit (V 2 ) of 1 4 da ys is use d.  
Part A is a n o pe n -la bel, ra n d o mize d, si n gle-d ose t w o treat me nt ar m 
c o m paris o n of t w o d ose  l e vels of s ustai ne d-release s u prac h or oi d al 
O X U -0 0 1 ( D E X A s p heres®  a d mi nistere d usi n g t he O x ul u mis ®  
ill u mi nate d micr ocat heterizati o n de vice).  
Part B is a ra n d o mize d, mas ke d, acti ve c o m parat or, si n gle -d ose, 
c o m paris o n  of t w o d ose l e vels of s u prac h or oi dal O X U -0 0 1 a n d I V T 
Oz ur de x ®  (0. 7 m g  de x a m et has o ne) t o e val uate t he safet y, t olera bilit y, 
effic ac y, a n d d ura bilit y i n s u bjects wit h D M E. 
I n Part A a n d Part B, a f oll o w-u p peri o d of 5 2  wee ks a p pears t o b e 
j ustifie d as precli nical e x peri me nts s u g gest a d ura bilit y of 9-1 2 m o nt hs 
bef ore f oll o w -o n treat me nt ma y be nee d e d.  

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T he st u d y p o p ulati o n will c o nsist of a t otal of a p pr o xi matel y 1 2 8 a d ult 
fe male or m ale s u bjects wit h D M E wit h a p pr o xi matel y 1 8 s u bjects 
i ncl u de d i n Part A a n d a p pr o xi matel y 1 1 0 s u bjects i ncl u de d i n Part B 
t hat: 
1.  Ha ve bee n dia g n ose d wit h T y pe 1 or T y pe 2 dia betes mellit us.  
2.  Ha ve D M E i n v ol vi n g t he ce nter of t he f o vea wit h ce ntral s u bfiel d 
t hic k ness ( C S T) i n t he st u d y e ye at t he scree ni n g visit, c o nfir me d b y 
t he C R C, of at least 3 2 0 µ m o n S D O C T ( meas ure me nt fr o m t he 
Reti nal Pi g me nt E pit heli u m, R P E , t o t he I n ner Li miti n g Me m bra ne, 
I L M, i ncl usi vel y). 
3.  Ha ve B C V A bet w ee n 3 4 a n d 7 8  letters ( usi n g a n E T D R S c hart, 
a p pr o xi mate S nelle n ac uit y of 2 0/ 2 0 0 – 2 0/ 3 2) i n t he st u d y e ye.  
4.  Are  treat me nt-naï ve or  pre vi o usl y  treate d wit h I V T a nti -V E G F i n 
t he st u d y e ye. 
O nl y o ne ( 1) e y e will be deter mi ne d as t he st u d y e ye a n d o nl y t he st u d y 
e ye will recei ve a si n gle a d mi nistrati o n of st u d y treat me nt o n Visit 2, 
Da y 0. St u d y e yes nee d t o meet all i ncl usi o n criteria a n d n o ne of t he 
e xcl usi o n criteria. If b ot h e yes meet t he rele va nt criteria, t he e ye wit h t he 
w orse B C V A will be selecte d as t he st u d y e ye; if b ot h e yes meet t he 
rele va nt criteria a n d ha ve t he sa me B C V A, t he i n v esti gat or ca n sel ect t he 
st u d y e ye. 
If o ne e y e is previ o usl y treate d (f or all o we d pri or treat me nts see Secti o n  
5. 2  a n d Secti o n 7. 8. 1 ), t he ot her e y e ma y still q ualif y as a treat me nt -
naï ve st u d y e ye if all i ncl usi o n criteria a n d n o n e of t he e xcl usi o n criteri a 
are met.  
S u bjects’ fell o w e ye ma y c o nti n ue t o recei ve n o n -st u d y treat me nt 
f oll o wi n g g ui deli nes a n d sta n dar ds at t he i n vesti gati o nal site. S u bjects i n 
Part A s h o ul d n ot recei ve ster oi d treat me nt i n t heir fell o w e ye, as t his 
ma y ha ve a n i m pact o n t he P K assess me nt of  O X U -0 0 1 . Treat me nt of t h e 
fell o w e ye is n ot c o nsi dere d part of t h e st u d y treat me nt. 
T he treat me nt ar ms i n Part A a n d Part B are as f oll o ws : 

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P art A  (O pe n L a bel ) c o nsists of t w o parallel , ra n d o mize d treat me nt ar ms, 
treate d wit h mi d -d ose, D M A 1. 5 m g (Ar m  A 1) a n d  hi g h d ose , D M A 3. 0 m g 
(Ar m  A 2) wit h a t otal of a p pr o xi matel y 1 8 s u bjects w h o are treat me nt -
naï ve or were pre vi o usl y treate d wit h I V T a nti -V E G F i n t he st u d y e ye  i n 
t he st u d y e y e. N o mi ni m u m n u m ber of treat me nt -naï ve s u bjects is fi xe d . 
S u bjects will be f oll o we d f or 5 2 wee ks  ( ma xi m u m ti me of partici pati o n 
f or a s u bject ca n be  u p t o 5 8  wee ks if t he ma xi m u m1 4 -da y  i nter val f or V 2 
acti vities is nee d e d ), wit h a safet y a nal ysis at Wee k 6, a n d f urt her a n al ys es 
at Wee k 2 4 , a n d Wee k 5 2.  
Treat me nt 
Ar m  
I nter ve nti o n 
S u bjects  
A 1  
O ne ( 1) tr eat me nt wit h s u prac h or oi d al mi d 
d ose ( D M A 1. 5 m g ) O X U-0 0 1  
N = 9  
A 2  
O ne 
( 1) tr eat me nt 
wit h s u prac h or oi dal 
hi g h d ose ( D M A 3. 0 m g ) O X U-0 0 1  
N = 9  
P art B  (M as ke d ) c o nsists of t hree ( 3) ra n d o mize d mas ke d ar ms wit h a 
t otal of a p pr o xi matel y 1 1 0 s u bjects ( B 1, B 2, a n d B 3) w h o are eit her 
pre vi o usl y treate d or treat me nt -naï ve (i n t he st u d y e ye).  
Treat me nt 
Ar m  
I nter ve nti o n 
S u bjects  
B 1  
O ne ( 1) tr eat me nt 
wit h s u prac h or oi dal 
D ose 1 ( mi d d ose D M A 1. 5 m g ) O X U-0 0 1  
n = 4 4  
B 2  
O ne ( 1) tr eat me nt 
wit h s u prac h or oi dal 
D ose 2 (t bc. D M A  3. 0 m g or 0. 7 5 m g ), 
base d o n t h e o utc o me of Part A 6 wee ks) 
O X U -0 0 1  
n = 4 4  
B 3  
O ne 
( 1) treat me nt 
wit h i ntra vitreal 
Oz ur de x ®  ( de xa met has o ne 0. 7 m g ) 
n  = 2 2  
E nr oll me nt f or P art B will c o m me nce after a s afet y a nal ysis w he n t he 
last s u bject i n Part A  has c o m plete d t he Wee k 6 visit. T he f oc us of t he 
a nal ysis will be o n patie nt -rele va nt safet y e ve nts, i ncl u di n g e. g., t he 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 0  of  1 6 9  
occ urre nce rate of m o derate a n d se v ere o c ular A Es, A E SI, a n d oc ul ar 
S A Es re vie we d b y D M C, a n d S p o ns or.  
I n P art B t w o differe nt d ose le vels of O X U -0 0 1 will be a d mi nistere d, 
D ose 1 i n treat me nt ar m B 1 a n d D ose 2 i n treat me nt ar m B 2 c o m pare d t o 
I V T Oz ur de x 0. 7 m g  (treat me nt ar m B 3). D ose 1 is pla n ne d t o be 
O X U -0 0 1 1. 5 m g ( mi d -d ose) a n d D os e 2 O X U -0 0 1 3. 0 m g ( hi g h d ose). If 
p ote ntial safet y c o ncer ns arise fr o m t he wee k 6 a n al ysis  i n Part A wit h 
t he hi g h d ose (treat me nt ar m A 2), t h e d ose i n Part B ma y be a dj uste d t o 
a d mi nister t he mi d -d ose i n B 1 ( D ose 1, 1. 5 m g) a n d t he l o w d ose i n B 2 
( D ose 2, 0. 7 5 m g) O X U -0 0 1. S u bjects will be f oll o we d f or 5 2  wee ks  
(ma xi m u m ti me of partici pati o n f or a s u bject ca n be u p t o 5 8 wee ks if t he 
ma xi m u m  1 4 -da y i nter val f or V 2 acti vities is nee de d ). 
T he  O X U C T -1 0 2  trial will i ncl u de b ot h  s u bjects t hat are tr eat me nt-n aï ve 
a n d s u bjects t hat ha ve b ee n pre vi o usl y treat e d wit h a nti -V E G F t hera p y i n 
t he st u d y e ye. F or treat m e nt-naï ve s u bjects t he ot her (fell o w) e y e ma y 
recei v e treat me nt f or D M E acc or di n g t o sta n dar d-of -care. I n Part A 
fell o w e ye tr eat me nt f or D M E wit h I V T ster oi ds is f or bi d de n, as it mi g ht 
i nterfere wit h P K assess me nts. 
I n Part A, su bje cts will be ra n d o ml y assi g ne d t o r ecei ve eit her a mi d -
d ose ( 1. 5 m g)  or hi g h d os e ( 3. 0 m g) O X U -0 0 1 i n a 1: 1 fas hi o n.  A 
ra n d o mize d parallel-gr o u p desi g n a p pears j ustifie d as t here is a m ple 
e x perie n ce wit h s ustai ne d -release f or m ulati o ns of de xa met has o ne i n 
reti nal dis or ders a n d t h e release ki netics a n d t he d ose ra n ge of t he 
pr o p ose d h u ma n d osa g e s ( 1. 5 a n d 3. 0 m g  s ustai ne d-release O X U-0 0 1 ) 
ha ve  bee n m o de le d t o be c o m para ble wit h t he release ki netics of 
pre vi o usl y  i n vesti gati o nal i ntra vitreal de xa met h as o ne 0. 3 5 m g  a n d t he 
mar kete d 0. 7 m g  i m pla nt. 
I n Part B, b ot h treat me nt-naï ve a n d a nti -V E G F pr e vi o usl y treate d 
s u bjects (i n t he st u d y e ye) will be e nr olle d ( n = 1 1 0). E nr oll me nt  of 
pre vi o usl y treate d a n d treat me nt -naï ve s u bjects will be c o m petiti ve, wit h 
at least 5 5 s u bjects  bei n g  treat me nt-naï ve  i n t he st u d y e ye. E nr oll me nt of 
s u bjects t hat are a nti-V E G F pre vi o usl y treate d i n t he st u d y e ye will st o p  
o nce 5 5  s u bjects wit h pre vi o us a nti -V E G F treat me nt i n t he st u d y e ye are 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 1  of  1 6 9  
ra n d o mize d t o all o w reac hi n g t he f oresee n n u m ber of treat me nt-n aï ve 
s u bjects. S u bjects will be stratifie d base d o n t heir a nti-V E G F treat me nt 
hist or y.  
I n b ot h  Part A a n d Part B, su bjects i n w h o m t he a d mi nistrati o n  of st u d y 
treat me nt c o ul d n ot be c o m plete d, will be re place d i n or der t o reac h t he 
tar gete d n u m bers of treat e d s u bjects . 
T he f oll o wi n g mas ki n g pr oce d ures will a p pl y i n Part B: 
S u bjects will be mas ke d t o t heir assi g n me nt t o o ne of t he treat me nt ar ms 
( B 1-B 3). S u bjects will o nl y recei ve o ne st u d y treat me nt  o n Visit 2, 
Da y  0 , i.e., eit her s u prac h or oi dal a d mi nistrati o n of st u d y treat me nt 
( O X U-0 0 1) or I V T Oz ur de x. N o s ha m treat me nt f or t he res pecti ve ot her 
treat me nt will be a p plie d.  
I n t his trial, t he a d mi nistrati o n of O X U-0 0 1 wit h t he O x ul u mis 
ill u mi nate d micr ocat heter will be perf or me d wit h t w o differe nt 
pr oce d ur al varia nts  d e pe n di n g o n s u bject c haracteristics a n d pr oce d ural 
s uccess: 
•  Sta n dar d  Vari a nt : A d mi nistrati o n wit h t he O x ul u mis ® de vice 
wit h o ut a n i ncisi o n of t he c o nj u ncti va/te n o ns. T he sta n dar d 
varia nt ca n b e perf or me d i n a n y setti n g, i.e., i n-cli nic, i n a 
pr oce d ure r o o m or i n a n o perati n g r o o m.  
•  C o njI ncisi o n  Varia nt : I ncisi o n of t he c o nj u ncti va /te n o ns at t he 
start of t he O X U-0 0 1 a d mi nistrati o n  t o i ncrease visi bilit y a n d 
access f or t he scl eral e n g a ge me nt p hase of t he O X U -0 0 1 
a d mi nistrati o n . T he i ncisi o n o pe ni n g of t he c o nj u ncti va/te n o ns 
nee ds t o be cl ose d b y usi n g sta n dar d s ur gical tec h ni q ues a n d 
material ( e. g., fi bri n gl ue, s ut uri n g material): T his varia nt ca n b e 
use d at t he discreti o n of t he  treati n g p h ysicia n ( u n mas ke d 
i n vesti gat or i n Part B) eit her a) i nitiall y if s u bject c haracteristics 
a n d/ or me dical hist or y s u g gest t his varia nt, or  b)  if wit h t he 
Sta n dar d  V ari a nt, st u d y treat me nt ca n n ot b e a d mi nistere d . 
T he C o njI n cisi o n  Varia nt ca n o nl y be perf or me d  i n a s ufficie ntl y 
e q ui p pe d e n vir o n me nt f or o pe ni ng a n d cl osi n g t he 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 2  of  1 6 9  
c o nj u ncti va/te n o ns. A n a de q uate pr oce d ural setti n g, tec h ni q ues 
a n d material use d  f oll o ws t he s ur gical sta n dar d i n t he res pecti ve 
ge o gra p hic re gi o n ( i.e., a n a de q uatel y e q ui p pe d pr oce d ure r o o m 
or a n o perati n g r o o m).  
T he treati n g p h ysicia n will deter mi ne at t he S cree ni n g V isit ( V 1), if 
i nitiall y t he Sta n dar d Varia nt or t he C o njI n cisi o n  Varia nt will be use d i n 
a res pecti ve s u bject. T h e baseli ne visit acti vities will be pla n ne d 
acc or di n gl y  wit h t hree differe nt sc he d ules f or bas eli ne visit acti vities:  
•  O X U -0 0 1 Sta n dar d Vari a nt  wit h o ut  s ur gical i ncisi o n is t y picall y 
perf or me d i n a n i n -cli nic or pr oce d ure r o o m s etti n g  
•  O X U -0 0 1 C o njI ncisi o n  Varia nt  wit h c o nj u ncti va/te n o ns i ncisi o n is 
t y picall y perf or me d i n a s ur gicall y e q ui p pe d pr o ce d ure or o perati n g 
r o o m 
•  M o ve  fr o m O X U-0 0 1 Sta n dar d t o C o njI ncisi o n  Vari a nt. I n t his 
sce nari o pr o ce d ural atte m pts are t y picall y starte d i n-cli nic. If t he 
O X U -0 0 1 Sta n dar d Vari a nt ca n n ot be c o m plete d, t he pr oce d ure is 
s witc he d t o t he C o njI n cisi o n  Varia nt  a n d de p e n di n g o n t he facilit y 
will t he n  be eit her perf or me d i n t he sa me facilit y  (s ur gicall y 
e q ui p pe d pr oce d ure r o o m)  or has t o be resc he d ul e d i n a s ur gical 
facilit y, w hic h ma y n ot b e a vaila ble t he s a me da y d ue t o sc he d uli n g 
or pr o xi mit y t o t he cli nic/ i n vesti gati o nal site. 
T he ma xi m u m ti me i nter val t o c o m plete all baseli ne visit acti vities is 
1 4   da ys i ncl u di n g p ote ntial resc he d uli n g of tr eat me nts i n case s witc h of 
t he pr oce d ural vari a nts is nee de d. 
I n Part B, if a n  u n mas ke d treati n g p h ysicia n deci des directl y f or t h e 
C o njI ncisi o n  Varia nt , a facilit y t hat all o ws i ncisi o n of t he 
c o nj u ncti va/te n o ns will be b o o ke d f or m as ki n g p ur p oses e ve n if t h e 
s u bject will be fi nall y ra n d o mize d t o recei ve Oz ur de x ® . F or Oz ur de x ®  
t he C o njI ncisi o n  P r oce d ural V aria nt, i.e., s ur gical i ncisi o n of t he 
c o nj u ncti va/te n o n is n ot all o we d.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 3  of  1 6 9  
In Part B , t he assess me nt tea ms at t he i n vesti gati o nal site perf or mi n g t he 
effic ac y  a n d s electe d q u esti o n naire  assess me nts  (i. e., B C V A, S u bject’s 
E x perie nce Assess me nt , a n d N EI -V F Q 2 5)  are f ull y mas ke d t o t he 
s u bject’s treat me nt assi g n me nt, as well as t he gra ders at t he ce ntral 
rea di n g c e nter assessi n g t he C S T val ues ( C R C). T his ma y re q uire  
s pecific rea ders f or ot her i ma gi n g li ke C ol or F u n d us P h ot o gra p h y ( C F P ) 
4 Wi de -Fi el d I R Pl us i ma ges, or peri p heral O C T , as t h ose assess me nts 
ma y s h o w fi n di n gs ( e. g., s u prac h or oi dal dr u g de p osits) t hat gi ve hi nts o n 
t he treat me nt assi g n me nt. St u d y treat me nts will be a d mi nistere d b y 
u n mas ke d  reti nal p h ysici a ns trai ne d o n t he O x ul u mis pr oce d ure, w h o 
will nee d t o k n o w t he treat me nt assi g n me nt of s u bjects  (f or details o n t he 
mas ki n g see Secti o n 7. 3 ). 
O n Visit 2 ( Da y 0), f or b ot h Parts A a n d B, s u bjects will recei ve st u d y 
treat me nt usi n g eit her t he 
O X U -0 0 1 Sta n dar d , or t he 
O X U -0 0 1 
C o njI ncisi o n  Varia nt as o utli ne d a b o ve wit h i m p act o n sc h e d uli n g of t he 
baseli ne visit acti vities as s u m marize d i n Ta ble 3  a n d Ta ble 4  of t he 
Sc he d ule of Acti vities. I n a d diti o n t o t he scree ni n g a n d baseli ne visits, 
( Visits 1 a n d 2, res pecti vel y), cli nic visits will occ ur o n Da y 1, a n d Wee k 
1, 4 , 6,  8,  a n d t he n e ver y f o ur  ( 4) wee ks t hereafter f or a t otal d urati o n of 
fift y-t w o ( 5 2) wee ks. 
I n Part A, t he Wee k 6 visit is sc he d ule d t o ca pt ure a n d assess a n y p ote ntial 
safet y si g nals w hic h ma y start  ar o u n d t his ti me after ster oi d treat me nt  
(e. g., I O P i ncrease). A safet y re vie w will occ ur after all acti ve st u d y 
partici pa nts ha ve c o m plete d Wee k 6 visit  pri or t o i nitiati ng ra n d o mizati o n 
i n Part B. 
F or P art B, t he Wee k 6 safet y visit is o pti o nal a n d  ma y be sc he d ul e d at t he 
discreti o n of t he i n vesti gat or  base d , e. g., if s u bjects te n d t o prese nt wit h 
rele va nt I O P i ncrease t hr o u g h Wee k 4 p ost-tr eat m e nt. 
Starti n g at t he Wee k 1 2 visit, f or b ot h Parts A a n d B, s u bjects will be 
e val uate d b y t he  i n vesti gat or ( mas ke d i n vesti gat or i n Part B) a gai nst 
pres pecifi e d criteria i n dicati n g t he nee d f or f oll o w -o n  treat me nt (i.e., 
i n dicati n g t he e n d of t he c urre nt treat me nt i nter val). Criteria are as f oll o ws: 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 4  of  1 6 9  
1.  At least 7 5 µ m t hic ke ni n g i n C S T o n S D -O C T c o m pare d t o best C S T 
val ue si nce t he baseli ne visit, Visit 2, Da y 0,  
 
or  
2.  A decrease i n B C V A of ≥1 0 letters ( E T D R S) fr o m t he best ac hie ve d 
B C V A si nce t he baseli ne visit, Visit 2, Da y 0, t hat, i n t he o pi ni o n of 
t he i n vesti gat or, is d ue t o t he w orse ni n g of D M E. 
F or s u bjects s h o wi n g n o re d ucti o n of e d e ma or n o i m pr o ve me nt of B C V A  
after Visit 2, Da y 0 , t h e val ues assesse d at t he  baseli ne visit will be 
c o nsi dere d t he b est C S T or B C V A val ue.  
If acc or di n g t o t he assess me nt of t he a b o ve criteria, b y t he i n vesti gat or 
( mas ke d i n vesti gat or i n Part B), t he nee d f or a d mi nistrati o n of f oll o w-o n 
treat me nt is i n dicate d, s u bjects will be ma na ge d acc or di n g t o l ocal 
sta n dar d of care f or t he rest of t he trial d urati o n. Sta n dar d of care  
treat me nts ma y i ncl u de I V T a nti-V E G F, oc ular I V T ster oi ds , or ot her n o n-
i n vesti gati o nal treat me nts.  
I n Part B, w he n f oll o w -o n  treat me nt criteria are met base d o n mas ke d 
assess me nt, t he u n mas ke d  i n vesti gat or will deter mi ne t he ki n d of f oll o w-
o n treat me nt t o be a d mi nistere d  (e. g., I V T a nti-V E G F tr eat me nt, I V T 
ster oi d, or ot her) c o nsi deri n g t he treat me nt hist or y a n d t he res p o ns e t o t he 
st u d y treat me nt recei ve d. After recei vi n g t he first f oll o w-o n treat me nt i n 
t he st u d y e ye, s u bjects will c o nti n ue o n t he re g ular visit sc he d ule t hr o u g h 
t he E n d-of -St u d y  ( E o S) visit at Wee k 5 2 . 
T his trial i ncl u des a d ata m o nit ori n g c o m mittee ( D M C). T he D M C's mai n 
res p o nsi bilit y is t o peri o dicall y  re vie w u n mas ke d trial data a n d pr o vi de 
rec o m me n dati o ns re gar di n g t he st u d y t o t he S p o ns or. Details will be 
descri be d i n t he D M C c harter.  
I n Part A, w h ol e bl o o d sa m ples will be c ollecte d f or meas ure m e nt of 
plas ma c o nce ntrati o ns of de xa met has o ne  o n Visits 1, 2, 3, 4, 5, 1 1, a n d 
1 8 (scree ni n g, Da y 0, at 6 0 mi n p ost -d ose, Da y 1, W ee k 1, 4, 2 4, a n d 5 2, 
res pecti vel y) as s pecifie d i n t he S o As i n Secti o n 1. 3  t o assess s yste mic 
e x p os ure of de xa met has o ne after a d mi nistrati o n of O X U -0 0 1 . 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 5  of  1 6 9  
Brief 
S u m m ar y  
T his is a fift y -t w o-wee k ( 5 2 -wee k) st u d y wit h a ra n d o mize d o pe n -la bel 
Part A  e nr olli n g  a p pr o xi matel y 1 8  D M E s u bjects,  treat me nt-naï ve or 
pre vi o usl y treate d i n t he st u d y e ye, f oll o we d b y a ra n d o mize d mas k e d 
Part B . Part B will i ncl u de a t otal of a p pr o xi matel y 1 1 0 D M E s u bjects  
( 5 5 treat me nt-n aï ve a n d 5 5 a nti -V E G F pre vi o usl y treate d  i n t he st u d y 
e ye). 
T he o bjecti ve of t h e st u d y is t o assess t he safet y, t olera bilit y, efficac y, 
a n d d ura bilit y of t w o d ose  le vels of s ustai ne d-release de xa m et has o ne 
micr os p heres ( D E X As p h ere s® , O X U-0 0 1) deli vere d t o t he 
s u prac h or oi dal s p ace wit h t he O x ul u mis ®  micr ocat heter c o m pare d t o 
i ntra vitreal de xa m et has o ne i m pla nt ( O Z U R D E X® ). 
P art A:  1 8 D M E s u bjects are ra n d o mize d t o r ecei ve a si n gle 
treat me nt wit h O X U-0 0 1 ( 1: 1) mi d -d ose ( Ar m A 1, N = 9) or 
O X U -0 0 1 hi g h d ose ( Ar m  A 2, N = 9).  
D ose gr o u ps will be e nr olle d i n parallel. 
P art B:  Parallel e nr oll me nt i n t he t hree treat me nt ar ms of Part  B 
will start o nce a safet y e val uati o n of Part A (at least 6 wee ks of dat a 
of all treate d s u bjects) has bee n c ollect e d a n d re vi e we d b y t he 
D M C a n d S p o ns or.  
Part B will i ncl u de a p pr o xi matel y 1 1 0 s u bjects t o recei v e o ne of 
t hree ra n d o ml y assi g ne d si n gle treat me nts ( 2: 2: 1),  
O X U -0 0 1 D os e 1 ( B 1, 1. 5 m g) ( N = 4 4), O X U -0 0 1 D ose 2 
(B 2 , 3. 0 m g or 0. 7 5 m g  de pe n di n g o n t he Part A si x -wee k s afet y 
re vie w) ( N = 4 4), or Oz ur de x (B 3, N = 2 2).  
After si g ni n g a n i nf or me d c o nse nt f or m (I C F) a n d c o m pleti n g t he 
scree ni n g pr oce d ures o n Visit 1 ( Da y-3 0  t o Da y-2), d uri n g Visit 2 ( Da y  0), 
s u bjects i n Part A will be ra n d o ml y assi g ne d t o recei ve eit her mi d -d ose 
( 1. 5 m g) or hi g h d os e  ( 3. 0 m g) O X U -0 0 1  i n a 1: 1 fas hi o n (at l east n = 9 f or 
eac h ar m) . 
I n Part B, s u bjects will be ra n d o ml y assi g ne d t o o ne of t hree st u d y ar ms: 
Ar m B 1; Ar m B 2, or Ar m B 3, recei vi n g O X U -0 0 1 D ose 1 ( 1. 5 m g), 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 6  of  1 6 9  
O X U -0 0 1 D ose 2 ( 3. 0 m g or 0. 7 5 m g  base d o n a Part A Wee k 6 s afet y 
re vie w) or Oz ur de x®  0. 7 m g at a rati o of 2: 2: 1, res pecti vel y.  
Cli nic visits will occ ur o n Da ys -3 0  t o -2 (scree ni n g), Da y 0 ( baseli ne a n d 
treat me nt visit), D a y 1, a n d Wee ks 1, 4, 6, 8,  a n d t he n e v er y f o ur  ( 4) wee ks 
t hereafter f or a t otal of fift y-t w o ( 5 2) wee ks after treat me nt c o m pleti o n.  
I n Part A, t he visit sc he d ule d f or Wee k 6 is ma n dat or y a n d will  ser ve t o 
assess a n y s afet y si g nals ( e. g., I O P i ncrease) o bs er ve d. A safet y re vie w 
will occ ur after all acti ve st u d y partici pa nts ha v e c o m plete d Wee k 6 visit 
pri or t o i nitiati n g ra n d o mizati o n i n Part B.  
F or P art B, t he Wee k 6 safet y visit is o pti o nal a n d ma y be sc he d ul e d at t he 
discreti o n of t he i n vesti gat or base d, e. g., if s u bjects te n d t o prese nt wit h 
rele va nt I O P i ncrease t hr o u g h Wee k 4 p ost-tr eat m e nt. 
Starti n g at t he Wee k 1 2 visit, s u bjects  will be assesse d usi n g pre -s pecifie d 
criteria f or t he nee d f or f oll o w -o n treat me nt. If s u bjects s h o w a nee d f or 
f oll o w-o n treat me nt, t he y will be treate d f oll o wi n g t he sta n dar d of care at 
t he res pecti ve st u d y site. 
T he pri mar y o utc o me m eas ure of t his st u d y is h o w fre q ue ntl y ( oc ular) 
a d verse e ve nts, A E SIs, a n d S A Es occ ur i n eac h ar m. Ot her o utc o m e 
meas ures i ncl u de ti me t o f oll o w-o n treat me nt , t he c ha n ge i n B C V A , a n d 
C S T . 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 7  of  1 6 9  
Eli gi bilit y 
Criteri a  
I n cl usi o n Criteria: S u bjects are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if 
A L L of t he f oll o wi n g crit eria a p pl y:  
1.  A ble t o u n dersta n d a n d si g n a n i nf or me d c o ns e nt f or m . 
2.  At least ei g htee n ( 1 8) years of a g e at t he ti me of s cree ni n g.  
3.  Ha ve bee n dia g n ose d wit h T y pe 1 or T y pe 2 dia betes mellit us . 
4.  Ha ve D M E i n v ol vi n g t h e ce nter of t he f o vea wit h ce ntral s u bfiel d 
t hic k ness ( C S T) i n t he st u d y e ye at t he s cree ni n g visit, c o nfir me d b y 
t he C R C, of at least 3 2 0 µ m o n S D O C T ( meas ure me nt fr o m t h e 
Reti nal Pi g me nt E pit heli u m, R P E, t o t he I n ner Li miti n g Me m bra ne, 
I L M, i ncl usi vel y). 
5.  Ha ve B C V A i n t he st u d y e ye bet w ee n 3 4 a n d 7 8 l etters E T D R S 
(a p pr o xi mate S nelle n ac uit y of 2 0/ 2 0 0-2 0/ 3 2) at t he scree ni n g visit. 
F or eli gi bilit y assess me nts, o nl y t he E T D R S B C V A letter  sc ore is 
c o nsi dere d rele va nt.  
6.  F or w o me n w h o are n ot p ost me n o pa usal ( i.e., at l east  1 2 m o nt hs of 
n o n -t hera p y-i n d u ce d a m e n orr hea or s ur gicall y sterile (a bse n ce of 
o varies a n d/ or uter us) ) a gree me nt t o r e mai n a bsti ne nt or use 
c o m bi ne d c o ntrace pti ve met h o ds t hat res ult i n a fail ure rat e of less 
t ha n 1 % per year fr o m t he treat me nt visit ( Visit 2, Da y 0) u ntil t he 
e n d of trial partici p ati o n, or , if s u bjects disc o nti n ue trial partici pati o n 
pri or t o Wee k 5 2 c o m pleti o n,  f or at least 5 2 wee ks fr o m t he 
treat me nt visit ( Visit 2, Da y 0) . E xa m ples of c o ntrace pti ve met h o ds 
wit h a n e x pect e d fail ure rate of less t ha n 1 % p er year i ncl u de m ale 
sterilizati o n, h or m o nal i m pla nts, pr o per use of c o m bi ne d oral or 
i njecte d h or m o nal c o ntr ace pti ves, a n d certai n i ntr a uteri ne de vi ces. 
Alter nati vel y, t w o met h o ds ( e. g., t w o barrier met h o ds s uc h as a 
c o n d o m a n d a cer vical ca p) ma y be c o m bi ne d t o ac hie ve a fail ure 
rate of less t ha n 1 % per year. Barrier met h o ds m ust al wa ys be 
s u p ple me nte d wit h t he use of a s per mici de. 
7.  Males m ust a gree t o use a barri er met h o d of c o ntr ace pti o n starti n g 
fr o m t he treat me nt visit ( Visit 2, Da y 0) u ntil t he e n d of trial 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 8  of  1 6 9  
partici pati o n, or , if s u bjects disc o nti n ue trial partici pati o n pri or t o 
Wee k 5 2  c o m pleti o n,  f or at least 5 2 wee ks fr o m t he treat me nt  visit 
( Visit 2, Da y 0) . 
8.  S u bject m ust be willi n g n ot t o partici pate i n a n y ot her cli nical trial 
i ncl u di n g a n i n vesti gati o nal me dici nal pr o d uct (I M P) or a n 
i n vesti gati o nal de vice u ntil t he e n d of trial partici pati o n.  
E xcl usi o n Criteria : S u bjects are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if 
N O N E of t he f oll o wi n g criteria a p pl y:  
1.  
Prese nce of a n y si g nifica nt oc ular or n o n -o c ular disease/ dis or der 
( or me dicati o n a n d/ or l a b orat or y test a b n or m alities) w hic h, i n t he 
o pi ni o n of t he I n v esti gat or a n d wit h t he c o nc urre nce of t he 
O x ular Me dical M o nit or, ma y  
1.  
p ut t he s u bject at ris k beca use of partici pati o n i n t he trial, 
or  
2.  
i nfl ue nce t he res ults of t he trial, or 
3.  
i nfl ue nce t he s u bject’s a bilit y t o partici pate i n t he trial, or 
4.  
ma y re q uire m e dical or s ur gical i nter ve nti o n d uri n g st u d y 
partici pati o n ( e. g., cataract, vitre o us he m orr h a ge, reti nal 
detac h me nt, or mac ular h ole).  
2.  
Mac ular e de ma c o nsi dere d d ue t o a ca use ot her t ha n dia betes 
mellit us i n eit her e ye.  
3.  
C o n diti o n, i n t he st u d y e ye, i n w hic h vis ual ac uit y is n ot e x pecte d 
t o i m pr o ve fr o m t he res ol uti o n of mac ular e de ma (e. g., f o veal 
atr o p h y, cli nicall y rele va nt l oss of elli ps oi d z o ne,  pi g me nt 
a b n or malities, vitre o mac ular tracti o n, or n o nreti nal ca uses)  as 
deter mi ne d b y t he  i n vesti gat or wit h c o nc urre n ce of t he O x ular 
Me dical M o nit or s u p p orte d b y a re vi e w b y t he C R C . 
4.  
C o n diti o ns i n t he st u d y e ye t hat ma y re n d er t he a d mi nistrati o n of 
st u d y treat me nt, i ntra vitreal i m pla nt i nserti o n, or s u prac h or oi d al 
micr ocat heter i nserti o n a n d de pl o y me nt diffic ult or s u bject t he 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 2 9  of  1 6 9  
patie nt t o e xcessi ve ris k of c o m plicati o ns. E xa m ples i ncl u de b ut 
are n ot li mite d t o oc ular s urface disease wit h si g nifica nt 
c o nj u ncti val e de ma a n d/ or i nfla m mati o n, oc ular h y p ot o n y, scleral 
sta p h yl o mas, necr otizi n g scleritis, scleral melti n g, e xcessi ve 
c h or oi dal scarri n g e. g., ass ociate d wit h pa n -reti nal 
p h ot oc oa g ulati o n, a m o n gst ot hers.  
5.  
Mac ular  
las er  
p h ot oc oa g ulati o n  
or  
p a nreti nal  
laser 
p h ot oc oa g ulati o n ( P R P) i n t he st u d y e y e perf or me d wit hi n si xtee n 
( 1 6) wee ks pri or t o scree ni n g. 
6.  
Acti ve pr oliferati ve dia betic reti n o pat h y ( P D R) or s e q uelae of 
P D R (i ncl u di n g iris ne o vasc ularizati o n, vitre o us he m orr ha g e, 
tracti o nal reti nal detac h me nt, e xte nsi ve scarri n g f oll o wi n g P R P) at 
scree ni n g i n t he st u d y e y e.  
7.  
Hist or y of rec urre nt or acti ve i ntra oc ular i nfla m mati o n i n eit her 
e ye (e. g., u v eitis) wit hi n t wel ve ( 1 2) wee ks pri or t o scree ni n g.  
8.  
I nfecti o us e ye dise ase li ke i nfecti o us ble p haritis, keratitis, or 
c o nj u ncti vitis i n eit her e ye wit hi n f o ur ( 4) wee ks of scree ni n g.  
9.  
I O P ≥ 2 2 m m H g, or gla uc o mat o us disc c ha n ges (i.e., a c u p disc 
rati o greater t ha n 0. 8) i n t he st u d y e ye at scree ni n g . Hist or y of 
gla uc o ma s ur ger y, a n d /or c urre nt a nti -gla uc o ma t hera p y wit h m or e 
t ha n t w o acti ve s u bsta nces (i n se parate or a c o m bi nati o n 
pre parati o n) are e x cl usi o nar y.  
1 0.  
Hist or y of cl ose d -a n gle gla uc o ma.  
1 1.  
IO P  < 6 m m H g ( h y p ot o n y) i n t he st u d y e ye  at scree ni n g. 
1 2.  
S p herical e q ui v ale nt of t he refracti ve err or of −6 di o pters of 
m y o pia or w ors e ( pri or t o cat aract or refracti ve s ur ger y) at 
scree ni n g. 
1 3.  
Cataract or ot her me dia o pacit y t hat li mits t he a bilit y t o o btai n t he 
pla n ne d i ma gi n g assess m e nts.  
1 4.  
Hist or y of reti nal detac h me nt.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 3 0  of  1 6 9  
1 5.  
Pri or treat me nt wit h I V T a nti -V E G F i n t he st u d y e ye 
1.  
Treat me nt -n aï ve gr o u p ( Part A a n d B):  
A n y I V T a nti -V E G F tr eat me nts i n t he st u d y e ye are 
e xcl usi o nar y re gar dless of t he ti me i nter val si nce i njecti o n.  
2.  
Pre vi o usl y treate d gr o u p  ( Part A a n d B): 
S u bjects i n t he pre vi o usl y treate d gr o u p are e x cl u de d if 
t he y meet a n y of t he bel o w criteria f or t he st u d y e ye at 
scree ni n g:  
a)  S u bject has recei ve d less t ha n t hree ( 3) a nti -V E G F 
i njecti o ns si nce treat me nt i nitiati o n (at least t hree 
i njecti o ns m ust ha ve bee n recei v e d f or eli gi bilit y). 
b)  Ti me i nter val b et wee n t he first a nti -V E G F i njecti o n 
a n d scree ni n g is m ore t ha n si xt y-f o ur ( >6 4 ) wee ks. 
c)  Last i njecti o n wit h ra ni bi z u ma b or b e vaciz u ma b wit hi n 
f o ur ( 4) wee ks pri or t o scree ni n g. 
d)  Last i njecti o n wit h afli berce pt wit hi n ei g ht ( 8) wee ks 
pri or t o scree ni n g.  
e)  Last i njecti o n wit h farici ma b or br ol uciz u ma b wit hi n 
t wel ve ( 1 2) wee ks pri or t o scree ni n g. 
f) Pri or treat me nt 
wit h 
S U S VI M O ( P ort 
Deli ver y 
S yste m) i m pla nt is e xcl usi o nar y.  
1 6.  
Pri or oc ular treat me nt wit h ster oi d i njecti o ns ( peri oc ular, 
s u bte n o n, i ntra vitreal) or i ntra vitreal i m pla nts i n t he st u d y e ye  A 
hist or y of t o pical oc ular ster oi ds is n ot e xcl usi o nar y.  
1 7.  
Part A o nl y: Pri or oc ular treat me nt wit h ster oi d i njecti o ns 
( peri oc ular, s u bte n o n, i ntra vitreal) or i ntra vitreal i m pla nts i n t he 
fell o w e ye ( d ue t o p ote ntial i nterfere nce wit h P K meas ure me nts). 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 3 1  of  1 6 9  
1.  
Last i njecti o n (i ntra - or peri oc ular /s u bte n o n) wit h 
tria mci n ol o ne acet o ni de wit hi n 1 2 wee ks  bef ore 
scree ni n g. 
2.  
Last i njecti o n ( s u prac h or oi dal) ster oi ds, e. g., Xi pere ™, 
wit hi n t wel ve ( 1 2) wee ks bef ore s cree ni n g.  
3.  
Last i njecti o n (I V T) wit h de xa met has o ne i m pla nt 
( Oz ur de x® ) wit hi n 2 4 wee ks  bef ore scree ni n g.  
4.  
Pri or treat me nt wit h l o n ger d urati o n i m pla nts ( e. g., 
fl u oci n ol o ne acet o ni de I V T i m pla nt, Il u vie n) is 
e xcl usi o nar y . 
1 8.  
Pri or treat me nt wit h s u prac h or oi dal ster oi ds i n t he st u d y e ye is 
e xcl usi o nar y . 
1 9.  
C o nc urre nt use of s yste mic gl uc oc ortic oi d me dicati o ns or 
s yste mic ster oi ds wit hi n t wel ve ( 1 2) wee ks b ef ore scree ni n g is 
e xcl usi o nar y.  I ntr a nasal, i n hale d, a n d e xtr a-oc ul ar t o pical 
c ortic oster oi ds are all o we d.  
2 0.  
Pri or I V T or s u prac h or oi dal treat me nt wit h i n vesti gati o nal a ge nts 
i n eit her e y e (e. g., a ge nts wit h a nti -V E G F acti vit y, or c o m bi ne d 
p har mac ol o gic acti vit y, g e ne t hera pies, cell t hera pi es, or a n y ot her 
t hera pe utic m o dalit y) at a n y ti me.  
2 1.  
Partici pati o n i n a cli nical trial i n w hic h a n i n vesti gati o nal dr u g 
( wit h ot her r o utes of a d mi nistrati o n t ha n I V T or s u prac h or oi d al) 
was a d mi nistere d wit hi n 9 0 da ys of scree ni n g or 5 half -li ves of t he 
i n vesti gati o nal dr u g, w hic he ver is l o n ger. 
2 2.  
Treat me nt wit h ocri plas mi n (Jetrea ® ) at a n y ti me. 
2 3.  
Hist or y of vitre oreti nal s ur ger y (i ncl u di n g s ur ger y f or reti nal 
detac h me nt or scleral b u c kle) i n t he st u d y e ye. Vitrect o m y is o nl y 
e xcl usi o nar y, if wit hi n 1 2 wee ks pri or t o scree ni n g.  
2 4.  
A n y ot her pre vi o us o p ht hal mic s ur geries, u n c o m plicate d cat aract 
s ur ger y, or u nc o m plicate d tra u ma i n t he st u d y e y e wit hi n t wel ve 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 3 2  of  1 6 9  
( 1 2) wee ks pri or t o scree ni n g. C o m plicate d cataract s ur ger y or 
tra u ma t hat 
ma y i m pact access a n d/ or dr u g deli ver y t o t he 
s u prac h or oi dal s p ace are e xcl usi o nar y.  
2 5.  
Part B o nl y: A n y hist or y of s ur gical c o m plicati o ns i n t he st u d y e y e 
t hat ma y i ncrease t he ris k of a nteri or c h a m ber mi grati o n of 
i ntra vitreal i m pla nts (e. g., t or n or r u pt ure d p osteri or le ns ca ps ule, 
i m pla ntati o n of a n y iris-fi xate d or s clera-fi xat e d i ntra oc ular le nses, 
iri dect o m y) re gar dl ess of t he ti me i nter val bet wee n t he pr oce d ure 
a n d t he st u d y e nr oll me nt.  
2 6.  
H y perse nsiti vit y t o O X U -0 0 1, or a n y of t h e e xci pi e nts i n t he 
O X U -0 0 1  f or m ulati o n or O x ul u mis®  de vice c o m p o ne nts.  
2 7.  
Part B o nl y: H y perse nsiti vit y t o c o m p o ne nts of Oz ur de x ®  f or 
s u bjects. 
2 8.  
Acti ve mali g na nc y or hist or y of mali g na nc y wit hi n t he past fi ve 
( 5) years. 
2 9.  
U nc o ntr olle d dia betes wit h a he m o gl o bi n A 1c ( H b A 1c) > 1 2 % or 
a n y ot her u nc o ntr olle d s yste mic disease at scree ni n g.  
3 0.  
U nc o ntr olle d h y perte nsi o n, defi ne d as bl o o d press ure 
wit h a 
s yst olic val ue of ≥ 1 6 0 m m H g or a  diast olic val ue of ≥ 1 0 0  m m H g 
u p o n re peat assess me nt at scree ni n g.  
3 1.  
Hist or y of m y ocar dial i nfarcti o n, str o k e, tra nsi e nt isc he mic attac k, 
ac ute c o n g esti ve heart fail ure, or a n y ac ute c or o nar y e v e nt wit hi n 
9 0 da ys  bef ore scree ni n g.  
3 2.  
S u bjects w h o are pre g na nt or breastf ee di n g at t he scree ni n g visit, 
or w h o test p ositi ve f or pre g na nc y at t he scree ni n g visit or are 
u n willi n g t o use a de q uate birt h c o ntr ol met h o ds t o pre ve nt 
pre g na nc y t hr o u g h o ut t he st u d y.  
3 3.  
S u bjects w h o were pre vi o usl y ra n d o mize d i n t his trial, b ut i n 
w h o m a d mi nistrati o n of st u d y treat me nt c o ul d n ot be c o m plete d.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 3 3  of  1 6 9  
N u m ber of 
S u bjects  
A  t otal of a p pr o xi matel y o ne h u n dre d a n d t we nt y -ei g ht ( 1 2 8) s u bjects 
will be treate d o ver t he t w o parts ( A, B) of t h e tri al. T h is i ncl u des 
ei g htee n ( 1 8) s u bjects i n Part A a n d o ne h u n dre d a n d te n ( 1 1 0) s u bjects 
i n Part B. S u bjects i n w h o m t he a d mi nistrati o n  of st u d y treat me nt  c o ul d 
n ot be c o m plete d, will be re place d i n or der t o reac h t he tar gete d n u m b ers 
of treate d s u bjects . 
St u d y Ar ms & 
D ur ati o n  
T he d urati o n of t he st u d y f 1 or eac h s u bject will be a ma xi m u m of fift y -
ei g ht  ( 58 ) wee ks, w hi c h i ncl u des u p t o f o ur (4 ) wee ks of scree ni n g, a n u p 
t o   1 4 -da y  i nter val f or perf or mi n g acti vities of t he baseli ne visit V 2,  a n d 
a n u p t o fift y -t w o ( 5 2) wee ks p ost -treat me nt o bser vati o n peri o d.  
T he st u d y c o m prises t w o parts, Part A a n d Part B.  
P art A ( O pe n L a bel)  c o nsists of t w o parallel,  ra n d o mize d ar ms treate d 
wit h mi d -d ose, 1. 5 m g ( Ar m A 1) a n d hi g h d ose 3. 0 m g ( Ar m A 2) wit h a 
t otal of a p pr o xi matel y 1 8 s u bjects w h o are tr eat me nt-naï ve or pre vi o usl y 
treate d wit h I V T a nti-V E G F  i n t he st u d y e ye. 
Treat me nt 
Ar m  
I nter ve nti o n 
S u bjects  
A 1  
O ne  ( 1) treat me nt 
wit h s u prac h or oi dal  
mi d d ose (D M A 1. 5 m g)  O X U -0 0 1  
N = 9  
A 2  
O ne  ( 1) treat me nt 
wit h s u prac h or oi dal  
hi g h d ose (D M A 3. 0 m g)  O X U -0 0 1  
N = 9  
P art B  (M as ke d ) c o nsists of t hree ( 3) mas ke d ar ms wit h a t otal of 
a p pr o xi matel y 1 1 0 s u bjects ra n d o mize d t o t hree ar ms i n a 2: 2: 1 fas hi o n 
( B 1, B 2, a n d B 3). S u bjects i n Part B are tr eat m e nt-naï ve or pre vi o usl y 
treate d wit h a nti -V E G F  (i n t he st u d y e ye). 
Treat me nt 
Ar m  
I nter ve nti o n 
S u bjects  
B 1  
O ne ( 1) treat me nt 
wit h s u prac h or oi dal  
D ose 1 (mi d d ose D M A 1. 5 m g)  O X U -0 0 1  
n = 4 4  

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O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 3 4  of  1 6 9  
B 2  
O ne ( 1) treat me nt 
wit h s u prac h or oi dal  
D ose 2 (t bc. D M A 3. 0 m g or 0. 7 5 m g , base d 
o n Part A 6 wee ks) O X U -0 0 1  
n = 4 4  
B 3  
O ne 
( 1) 
treat me nt 
wit h 
i ntra vitreal 
Oz ur de x ®  ( de xa met has o ne 0. 7 m g ) 
n  = 2 2  
 
D at a 
M o nit ori n g 
C o m mittee  
A data m o nit ori n g c o m mittee ( D M C) will be  a p p oi nte d f or t his st u d y. T he 
c o m p ositi o n a n d res p o nsi bilities of t he c o m mittee are i ncl u de d i n t he 
D M C C harter.  

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1. 2  
St u d y Sc he m atic  
Fi g ure 1  St u d y O ver vie w P art A  
 
Fi g ure 2  St u d y O ver vie w P art B  
 
Ke y of a b bre viati o ns: E O S: E n d of St u d y , De xas p heres: O X U-0 0 1 . 
N ote s: 
1.  
I n Part B , D ose 1 i n Ar m B 1 will be O X U -0 0 1 1. 5 m g. De pe n di n g o n t he o utc o me of 
t he Wee k 6 Safet y Re vie w i n Part A, D ose 2 i n Ar m B 2 will be 3. 0 m g or 
0. 7 5 m g  O X U -0 0 1 . 
2.  
T he nee d f or f oll o w -o n tr eat me nt will be assesse d fr o m Wee k 1 2 o n , usi n g pre -defi ne d 
criteria (i n Part A a n d Part B). 

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b)  Partial re vie w o nl y: A list of eli gi bilit y criteria m ust be c o nfir me d (see Secti o n 5 ). B C V A a n d ce ntral s u bfiel d t hic k ness eli gi bilit y will be base d o n t he assess me nt at t he 
scree ni n g visit ( Visit 1). 
c) Vital si g ns i ncl u de meas uri n g b o d y te m perat ure, bl o o d press ure  a n d heart rate. Hei g ht will o nl y be meas ure d at scree ni n g.  
d)  Fe males of c hil d beari n g p ote ntial o nl y. A pre g na nc y test (ser u m  at scree ni n g a n d uri ne at all ot her visits ) m ust be ne g ati ve f or t he s u bject t o recei ve st u d y treat me nt. A d diti o nal 
pre g na nc y tests ma y be perf or me d at a n y ti me d uri n g t he st u d y as re q uire d.  
e) D u plicate meas ure me nts of B C V A i n t he st u d y e ye are ma n dat or y. F or t he fell o w e ye, d u plicate meas ure me nts at scree ni n g a n d si n gle meas ure me nts at all s u bse q ue nt visits . 
f) 
At e q ui p pe d sites o nl y.  
g)  I ma gi n g wit h S D-O C T de vices will i ncl u de 4 -Wi de -Fiel d Near i nfrare d (I R) Pl us i ma gi n g at sites e q ui p pe d wit h a Hei d el ber g S pectralis  de vice.  
h)  O n Da y 0, m o nit ori n g of s u bjects f or 6 0 mi n utes p ost -treat me nt wit h at least 2 meas ure me nts of I O P. Disc har ge o nl y if I O P is n or mal or I O P l o weri n g meas ures ha v e bee n 
ta ke n, total m o nit ori n g  ti me u ntil n or malizati o n ma y be l o n ger t ha n 6 0 mi n utes . 
i) 
F oll o w -o n treat me nt deter mi nati o n base d o n pres pecifie d criteria ( Secti o n 7. 5. 2 ). F oll o w-o n treat me nt will be a d mi nistere d if t he pres pecifie d criteria are met.  
j) 
F or s u bject s w h o deci de t o st o p partici pati o n i n t his trial , a n earl y ter mi nati o n visit wit h t he acti vities o utli ne d i n t his c ol u m n s h o ul d be perf or me d.  

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f) 
D u plicate meas ure me nts of B C V A i n t he st u d y e ye are ma n dat or y. F or t he fell o w e ye, d u plicate meas ure me nts at scree ni n g a n d si n gle meas ure me nts at all s u bse q ue nt visits.  
g)  At e q ui p pe d sites o nl y.  
h)  I ma gi n g wit h S D-O C T de vices will i ncl u de 4 -Wi de -Fiel d Near i nfrare d (I R) Pl us i ma gi n g at sites e q ui p pe d wit h a Hei d el ber g S pectralis  de vice.  
i) 
O n Da y 0, m o nit ori n g of s u bjects f or 6 0 mi n utes p ost -treat me nt wit h at least 2 meas ure me nts of I O P. Disc har ge o nl y if I O P is n or mal or I O P l o weri n g meas ures ha v e bee n 
ta ke n, total m o nit ori n g ti me u ntil n or malizati o n ma y be l o n ger t ha n 6 0 mi n utes . 
j) 
F oll o w -o n treat me nt deter mi nati o n base d o n pres pecifie d criteria as assesse d b y t he mas ke d i n vesti gat or (see Secti o n 7. 5. 2 ). F oll o w-o n treat me nt will be a d mi nistere d if t he 
pres pecifie d criteria are met.  T he decisi o n o n t he ki n d of f oll o w -o n treat me nt t o be a d mi nistere d will be ma de b y a n u n mas ke d i n vesti gat or, base d o n t he treat me nt hist or y 
a n d st u d y treat me nt recei ve d.  
k)  F or s u bject s w h o deci de t o st o p partici pati o n i n t his trial, a n earl y ter mi nati o n visit wit h t he acti vities o utli ne d i n t his c ol u m n s h o ul d be perf or me d . 

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Nati o nal e ye i nstit ute 2 5 -ite m vis ual f u ncti o n q uesti o n naire; O C T = oc ular c o here nce t o m o gra p h y; O R = O perati n g R o o m, ; O U = b ot h e yes; S D -O C T  =  s pectral-d o mai n oc ular 
c o here n ce t o m o gra p h y; S E = st u d y e y e;  n.a.  
( *) Pre-treat me nt, ( * *) P ost-(c o m plete d)treat me nt, ( * * *) p ost n o n -c o m plete d treat me nt sessi o n (see als o Secti o n 9. 2 )  
a) Visit dates a n d visit wi n d o ws are calc ulate d fr o m t he act ual date of c o m pleti n g t he st u d y treat me nt a d mi nistrati o n. T he st u d y treat me nt a d mi nistrati o n has t o occ ur wit hi n 1 4 
da ys after t he start of Visit 2 acti vities . If necessar y, t he 2n d treat me nt sessi o n als o has t o occ ur wit hi n t his 1 4 -da y  wi n d o w  ( St u d y Visit 2, Da y 0). O nl y f or t he visit wi n d o w of 
t he Scree ni n g Visit, a n e xte nsi o n of t he visit wi n d o w t o 3 7 da ys ca n be a p pr o ve d b y t he O x ular Me dical M o nit or base d o n a n i ndi vi d ual re q uest of t he i n vesti gat or stati n g 
i m p orta nt me dical a n d/ or or ga nizati o nal reas o ns. 
b)  Details of t he setti n g f or a d mi nistrati o n of st u d y treat me nts ma y var y bet wee n st u d y c o u ntries. T he O X U -0 0 1 Sta n dar d  varia nt of t he pr oce d ure  ca n be a d mi nistere d i n t he 
cli nic or i n a pr oce d ure r o o m. F or t his varia nt, t he pr oce d ure r o o m d oes n ot nee d s ur gical e q ui p me nt. F or t he O X U -0 0 1 C o njI ncisi o n  Varia nt , w hic h mea ns a n i ncisi o n of t he 
c o nj u ncti va/te n o ns t o facilitate  t he scleral e n ga ge me nt of t he de vice, a s ur gical setti n g is nee de d as t he c o nj u ncti va/te n o ns ha v e t o be o pe ne d a n d cl ose d, e. g., wit h fi bri n gl ue 
or s ut uri n g.  
c) Partial re vie w o nl y: A list of eli gi bilit y criteria m ust be c o nfir me d (see Secti o n 5 ). B C V A a n d ce ntral s u bfiel d t hic k ness eli gi bilit y will be base d o n t he assess me nt at t he 
scree ni n g visit ( Visit 1). 
d)  Fe males of c hil d beari n g p ote ntial o nl y. A pre g na nc y test (ser u m at scree ni n g a n d uri ne at all ot her visits) m ust be ne gati ve f or t he s u bject t o recei ve st u d y treat me nt. A 
pre g na nc y test m ust  be re p eate d i n case  assess me nts a n d st u d y treat me nt occ ur o n differe nt da ys, or i n Alter nati ve N o. 3, w he n t he O X U -0 0 1 C o njI ncisi o n  Varia nt is sc h e d ule d  
o n a n ot her da y. A d diti o nal pre g na n c y tests ma y be perf or me d at a n y ti me d uri n g t he st u d y as re q uire d.  
e) O n Da y 0, m o nit ori n g of s u bjects f or 6 0 mi n utes p ost -treat me nt, ( b ut n ot p ost treat me nt sessi o ns wit h n o d ose a d mi nistere d ,) wit h at least 2 meas ure me nts of I O P.  Disc h ar ge 
o nl y if I O P is n or mal or I O P l o weri n g meas ures ha ve bee n ta ke n , t otal m o nit ori n g ti me u ntil n or malizati o n ma y be l o n ger t ha n 6 0 mi n utes. 
f) 
D u plicate meas ure me nts of B C V A i n t he st u d y e ye are ma n dat or y. F or t he fell o w e ye, d u plicate meas ure me nts at scree ni n g a n d si n gle meas ure me nts at all s u bse q ue nt visits.  
g)  I ma gi n g wit h S D-O C T de vices will i ncl u de 4 -Wi de -Fiel d Near i nfrare d (I R) Pl us i ma gi n g at sites e q ui p pe d wit h a Hei d el ber g S pectralis  de vice.  
h)  At e q ui p pe d sites o nl y.  
i) 
I n A lter nati ve N o. 3, t he Sta n dar d Varia nt  i n-cli nic pr oce d ure ca n n ot be c o m plete d a n d t heref ore a re peat treat me nt sessi o n is nee de d usi n g t he O X U-0 0 1 C o njI ncisi o n  Varia nt. 
I n Alter nati ve N o. 2, treati n g p h ysicia ns ma y start wit h t he O X U -0 0 1 Sta n dar d  V aria nt at t heir o w n discreti o n  a n d m o ve t o t he C o njI ncisi o n  Varia nt  if nee de d. 
j) 
P har mac o ki netic sa m pli n g will o nl y be ma n dat or y, p ost d ose, w he n t he a d mi nistrati o n pr oce d ure has bee n c o m plete d s uccessf ull y . 
 
 

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c o here n ce t o m o gra p h y; S E = st u d y e y e;  n.a.  
( *) Pre-treat me nt, ( * *) P ost-(c o m plete d) treat me nt, ( * * *) P ost -( n o n-c o m plete d)  treat me nt sessi o n (see als o Secti o n 9. 2 )  
a) Visit dates a n d visit wi n d o ws are calc ulate d fr o m t he act ual date of c o m pleti n g t he st u d y treat me nt a d mi nistrati o n. T he st u d y treat me nt a d mi nistrati o n has t o occ ur wit hi n 
1 4 da ys after t he start of Visit 2 acti vities, If necessar y, t he 2 n d treat me nt sessi o n, als o has t o occ ur wit hi n t his 1 4-da y wi n d o w  ( St u d y Visit 2, Da y 0). O nl y f or t he visit 
wi n d o w of t he Scree ni n g Visit, a n e xte nsi o n of t he visit wi n d o w t o 3 7 da ys ca n be a p pr o ve d b y t he O x ular Me dical M o nit or base d o n a n i n di vi d ual re q uest of t he 
i n vesti gat or stati n g i m p orta nt me dical a n d/ or or ga nizati o nal reas o ns. 
b)  Details of t he setti n g f or a d mi nistrati o n of st u d y treat me nts ma y var y bet wee n st u d y c o u ntries. T he O X U -0 0 1 Sta n dar d  varia nt of t he pr oce d ure ca n be a d mi nistere d i n t he 
cli nic or i n a pr oce d ure r o o m. F or t his varia nt, t he pr oce d ure r o o m d oes n ot nee d s ur gical e q ui p me nt. F or t he O X U -0 0 1 varia nt C o njI ncisi o n  Varia nt , w hic h mea ns a n 
i ncisi o n of t he c o nj u ncti va/te n o ns t o facilitate t he scleral e n ga ge me nt of t he de vice, a s ur gical setti n g is nee de d as t he c onj u ncti va/te n o ns ha ve t o be o pe n e d a n d cl ose d, 
e. g., wit h fi bri n gl ue or s ut uri n g.  
c) Partial re vie w o nl y: A list of eli gi bilit y criteria m ust be c o nfir me d (see Secti o n 5 ). B C V A a n d ce ntral s u bfiel d t hic k ness eli gi bilit y will be base d o n t he assess me nt at t he 
scree ni n g visit ( Visit 1). 
d)  Fe males of c hil d beari n g p ote ntial o nl y. A pre g na nc y test (ser u m at scree ni n g a n d uri ne at all ot her visits) m ust be ne g ati ve f or t he s u bject t o recei ve st u d y treat me nt. A 
pre g na nc y test m ust be re p eate d i n case assess me nts a n d st u d y treat me nt occ ur o n differe nt da ys, or i n Alter nati ve N o. 3, w he n  t he O X U-0 0 1 C o njI ncisi o n  Varia nt is 
sc h e d ule d o n a n ot her da y. A d diti o nal pre g na nc y tests ma y be perf or me d at a n y ti me d uri n g t he st u d y as re q uire d.  
e) O n Da y 0, m o nit ori n g of s u bjects f or 6 0 mi n utes p ost -treat me nt, ( b ut n ot p ost treat me nt sessi o ns wit h n o d ose a d mi nistere d)  wit h at least 2 meas ure me nts of I O P.  Disc h ar ge 
o nl y if I O P is n or mal or I O P l o weri n g meas ures ha ve bee n ta ke n , t otal m o nit ori n g ti me u ntil n or malizati o n ma y be l o n ger t ha n 6 0 mi n utes. 
f) 
D u plicate meas ure me nts of B C V A i n t he st u d y e ye are ma n dat or y. F or t he fell o w e ye, d u plicate meas ure me nts at scree ni n g a n d si n gle meas ure me nts at all s u bse q ue nt 
visits.  
g)  I ma gi n g wit h S D-O C T de vices will i ncl u de 4 -Wi de -Fiel d Near i nfrare d (I R) Pl us i ma gi n g at sites e q ui p pe d wit h a Hei d el ber g S pectralis  de vice.  
h)  At e q ui p pe d sites o nl y.  
i) 
I n A lter nati ve N o. 3, t he Sta n dar d Varia nt i n-cli nic pr oce d ure ca n n ot b e c o m plete d a n d t heref ore a re peat treat me nt sessi o n is nee de d usi n g t he O X U-0 0 1 C o njI ncisi o n  
Varia nt. I n Alter nati ve N o. 2, u n mas ke d treati n g p h ysicia ns ma y start wit h t he O X U -0 0 1 Sta n dar d  V aria nt at t heir o w n discreti o n  a n d m o ve t o t he  C o njI ncisi o n  Varia nt if 
nee de d . 
 

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Pa ge 4 6  of  1 6 9  
2  
I ntr o d ucti o n 
2. 1  
St u d y R ati o n ale  
T here is a great u n met n ee d f or D M E t hera pies, w hic h  ha ve a br oa der s pectr u m of 
p har mac ol o gical acti vities  a n d t here b y als o  a d dres s t he str o n g i nfla m mat or y c o m p o ne nt of 
D M E. I n a d diti o n, t hera pies wit h a l o n g d urati o n of acti o n of m ore t h a n 6 m o nt hs w o ul d 
re d uce t h e treat me nt b ur de n of patie nts. Oc ul ar c ortic oster oi ds ha ve t he p ote ntial t o a d dress 
t his u n met nee d, as t he y ha ve n ot o nly s h o w n str o n g a nti-e de ma effect s si milar t o a nti-V E G F 
treat me nts, b ut als o a br oa d a nti-i nfla m mat or y effect. Pr o gressi ve reti nal a n d c h or oi dal 
i nfla m mati o n is a ke y dri ver of t he pr o gressi o n of dia betic e ye dise ase. 
Pr o vi de d a n acce pta ble s afet y pr ofile, o c ular ster oi ds ca n deli ver vis ual be n efits  i n D M E 
s u bjects t hat are tr eat me nt-naï ve as w ell as i n t h ose  w h o ha ve s h o wn  li mite d, s h ort-li ve d, n o 
vis ual i m pr o ve me nt wit h I V T a d mi nistere d a nti -V E G F dr u gs.  
T he use of c urre nt ster oi d t hera pies f or D M E, i ncl u di n g I V T Oz ur de x ® , is li mite d b y t he 
t y pical a n d fre q ue nt a d v erse reacti o ns; s pecificall y, cataract f or m ati o n a n d i ncreas e d 
i ntra oc ular press ure (I O P), w hic h us uall y re q uir e a d mi nistrati o n of a d diti o nal o p ht hal mic 
dr u gs, e. g., I O P l o weri n g e ye dr o ps; gla uc o m a s ur ger y or le ns re place me nt s ur ger y. D ue t o 
t hese safet y c o ncer ns a n d t he li mite d d ura bilit y of o nl y 3-6 m o nt hs f or t he m ost fre q ue ntl y 
use d I V T ster oi d i m pla nt , t here re mai ns a hi g h u n met me dical nee d f or effi caci o us oc ular 
treat me nts f or dia b etic mac ular e de ma ( D M E) wit h a m ore fa v ora ble be nefit -ris k pr ofile. 
O X U -0 0 1 is a c o m bi nati o n t hera p y of s ustai ne d-release d e xa met has o n e acetate micr os p heres 
(D E X A s p heres® ) a d mi nistere d s u prac h or oi dall y wit h t he O x ul u mis®  o p ht hal mic ill u mi nate d 
m icr ocat heterizati o n de vi ce  (a n o p ht h al mic a d mi nistrati o n de vice). Bas e d o n precli nical 
e x peri me nts, a f oll o w-u p peri o d of 5 2 wee ks a p p ears t o be j ustifie d as a t hera pe utic effect f or 
9 -1 2 m o nt hs is e x pecte d bef ore f oll o w -o n treat me nt ma y be nee d e d . O X U -0 0 1 is e x pecte d t o 
ha ve a s ustai ne d a nti -e de ma effect a n d a re d u ce d i nci de nce of s ter oi d-relate d oc ular a d v erse 
e ve nts ( A Es)  c o m pare d t o c urre nt sta n d ar d i ntra o c ular ster oi d treat me nts . 
T he c urre nt trial has t he o bjecti ve of ge n erati n g  cli nical data t o assess t he f oll o wi n g as pects of 
s u prac h or oi dal tr eat me nt wit h O X U -0 0 1 i n D M E:  

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1.  
T he safet y of s u prac h or oi dal, s ustai ne d -release ster oi d treat me nt i n D M E wit h res pect 
t o re d ucti o n of t he ris k of ster oi d-i n d uce d c o m plicati o ns b y p osteri or de pl o y me nt of 
t he O X U-0 0 1.  
2.  
T he t hera p e utic effects of O X U -0 0 1 t o pr o vi d e cli nicall y mea ni n gf ul vis ual a n d 
a nat o mical be nefits f or a n e xte n de d ti me ( > 6 m o nt hs) b y re d uci n g D M E . 
3.  
T he s yste mic e x p os ure t o de xa met has o ne f oll o wi n g s ustai ne d releas e s u prac h or oi dal 
a d mi nistrati o n f or t he d urati o n of t he cli nical trial.  
2. 2  
B ac k gr o u n d  
T he efficac y a n d safet y of oc ular ster oi ds i n t he ma na ge me nt of D M E are well d oc u me nte d. 
I n t heir rece nt C oc hra ne re vie w, Ritti p hair oj et al. re p orte d fi n di n gs fr o m 1 0 cli nical trials 
i n v ol vi n g 4, 5 0 5 e yes of 4, 3 4 8 s u bjects treate d wit h I V T ster oi ds c o m pare d t o ot her treat me nts 
(Ritti p hair oj et al., 2 0 2 0 ). Des pite p ote ntial efficac y wit h re gar ds t o vis ual ac uit y a n d 
re d ucti o n of ma c ular e d e ma, t he a ut h ors c o n cl u de d t hat be nefits fr o m I V T ster oi ds s h o ul d be 
wei g he d a g ai nst I O P ele v ati o n, t he use of I O P‐l o w eri n g me dicati o n, a n d, i n p ha kic patie nts, 
t he pr o gressi o n of cataracts. Si milar c o ncl usi o ns ha ve bee n rece ntl y p u blis he d i n a re vie w of 
I V T p har mac ot hera pies f or D M E b y a n a ut h or gr o u p fr o m t he A merica n Aca de m y of 
O p ht hal m ol o g y  (E hlers et al., 2 0 2 2 ). 
Acc or di n g t o t he O z ur de x ®  U S Prescri bi n g I nf or mati o n  (Aller ga n I nc. 2 0 1 4  (Versi o n 2 0 2 0 )), 
6 1 % of p ha kic p atie nts i n t he Oz ur de x
®  ar m i n D M E trials of 3 -year d urati o n, re q uire d 
cataract s ur g er y b y t he fi nal visit i n t he st u d y. Mea n I O P i n t he st u d y e ye at baseli ne was t he 
sa me i n b ot h treat me nt gr o u ps ( 1 5. 3 m m H g). T he mea n i ncrease fr o m baseli ne I O P di d n ot 
e xcee d 3. 2  m m H g acr oss all visits i n t he Oz ur de x ®  gr o u p wit h t he mea n I O P pea ki n g at t he  
1. 5 -m o nt h visit p ost  i njecti o n a n d ret ur ni n g t o a p pr o xi matel y baseli ne le vels b y m o nt h 6 
f oll o wi n g eac h i njecti o n. T he rate a n d ma g nit u de of I O P ele vati on f oll o wi n g Oz ur de x ®  
treat me nt di d n ot i ncreas e u p o n re peate d i njecti o n of Oz ur de x® . 2 8 % of patie nts treate d wit h 
Oz ur de x ®  ha d a ≥ 1 0 m m H g I O P i ncrease fr o m baseli ne at o ne or m or e visits d uri n g t he 
st u d y. At baseli ne 3 % of patie nts re q uire d I O P-l o weri n g me dicati o n(s). O verall, 4 2 % of 
patie nts re q uire d I O P -l o weri n g me dicati o ns i n t h e st u d y e ye at s o me sta g e d uri n g t he 3-year  
st u dies, wit h t he maj orit y of t hese patie nts r e q uiri n g m ore t ha n o ne me dicati o n.  
To o verc o me t h ese p ote ntial si de effects of oc ular ster oi ds, i.e., I O P ele vati o n, a n d cataract 
pr o gressi o n, se veral gr o u ps ha ve trie d t o deli ver tria mci n ol o ne acet o ni de ( T A), a c o m m o nl y 
use d ster oi d f or i ntra vitreal deli ver y t o ma na g e p osteri or se g me nt i nfla m mati o n, via t he 

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s u prac h or oi dal s p ace f or D M E a n d ot her reti nal pat h ol o gies. B y c ha n gi n g t he site of deli ver y 
fr o m t he vitre o us ca vit y t o t he s u prac h or oi dal s pace, t he tar g et tiss ues ass ociate d wit h t hese 
c o m plicati o ns ( i.e., le ns a n d a nteri or se g me nt of t he e ye) are e x pecte d t o be e x p ose d t o l o wer 
c o nce ntr ati o ns of ster oi ds, a n d he nce m a y be less pr o ne t o de vel o pi n g  t hes e si de effects. 
Rece ntl y, cli nical trials  (Wy k off et al., 2 0 1 8 ; Bara kat et al., 2 0 2 1 ) usi n g micr oi njecti o n 
tec h ni q ues i n t he pars pla na, c o nfir me d t h e cli nical feasi bilit y of s u prac h or oi dal deli ver y wit h 
a n acce pta ble s afet y pr ofile a n d g o o d efficac y. I n t he H U L K trial (Wy k off et al., 2 0 1 8 ), a n 
o pe n -la bel, 2 0 s u bje ct st u d y e val uati n g t he use of T A a p plie d t o t he s u prac h or oi dal s pace wit h 
a micr oi nject or i n t he ma na ge me nt of D M E, treat me nt -naï ve patie nts ( n = 1 0) ha d 8. 5 E T D R S 
letters i m pr o ve me nt at m o nt h  6, w hile t h ose pre vi o usl y treate d ( n = 1 0) i m pr o ve d o nl y  
1. 1 letters wit h 1 0 % of t h e patie nts ( n = 2 of 2 0) e x perie nci n g ≥  1 0 m m H g i ncreas e i n I O P 
d uri n g t he st u d y. T here w ere t hr ee cases of cataract pr o gressi o n. N ota bl y, t here was i njecti o n 
site pai n i n 1 of 2 0 patie nts a n d i na d verte nt i ntra vitreal dr u g de p osit in 1 of 2 0 patie nts.  
I n t he T Y B E E P hase 2 tri al (Bara k at et al., 2 0 2 1 ), 7 1 patie nts wit h D M E were ra n d o mize d t o 
recei v e eit her 4 m o nt hl y d oses of afli berce pt ( Da y 0, Wee ks 4, 8, a n d 1 2) f oll o we d f or t w o 
m ore m o nt hs wit h t he o pti o n t o recei ve pr o -re-nat a ( P R N) afli berce pt o n Wee ks 1 6 a n d 2 0 
(afli berce pt ar m), or 2 T A i njecti ons ( 4 m g) a d mi nistere d t o t he s u prac h or oi dal s pace ( Da y 0 
a n d wee k 1 2) wit h t he o pti o n f or P R N afli berce pt o n wee ks 4, 8, 1 6 a n d 2 0 (c o m bi nati o n 
ar m). T he pri mar y e n d p oi nt was t he mea n c h a n ge i n B C V A fr o m baseli ne at Wee k 2 4. Des pite 
a nat o mical i m pr o ve me nt  i n ter ms of C S T (-2 2 6. 5 µ m mea n c ha n ge at wee k 2 4) f or t he 
c o m bi nati o n ar m c o m pare d t o t he afli berce pt ar m ( -1 7 6. 1 µ m), t he c ha n g e i n B C V A at 
wee k  2 4 f or t he c o m bi nati o n ar m ( 1 2. 3 E T D R S letters) was n ot statisticall y differe nt fr o m t he 
afli berce pt ar m ( 1 3 . 5 E T D R S letters, test wit h t w o-si de d si g nifica nce le vel of 0. 1 0). I O P 
i ncreas e of m ore t h a n 3 0 m m H g occ urre d i n 3  patie nts i n t he acti ve gr o u p a n d 0 patie nts i n t he 
c o ntr ol gr o u p. I O P i ncreases of m ore t ha n 1 0 m m H g occ urre d i n 5 a n d 0 pati e nts i n t he acti ve 
a n d c o ntr ol gr o u ps, res pecti vel y (Bara k at et al., 2 0 2 1 ). 
T he use of micr o cat het er deli ver y t o t he s u prac h or oi dal s pace was re p orte d i n 1 1 patie nts 
(e yes) wit h a d va nce d ne o vasc ular A M D t hat faile d c o n ve nti o nal t hera p y (C ha n g 2 0 0 9 ). 
Treat me nt c o nsiste d of a si n gle d ose of be vaciz u m a b ( Avasti n) a n d/ or tria m ci n ol o ne 
a d mi nistere d b y s u prac h or oi dal cat heterizati o n. M ost  patie nts recei ve d a c o m bi nati o n of 
be vaciz u m a b ( Avasti n) a n d tria mci n ol o ne. T he a v era ge pre o p erati ve B C V A was 
1. 7 8  ±  0. 4 1 l o g M A R  u nits, w hic h i ncrease d t o 1. 4 0  ±  0. 6 0 at t hree m o nt hs a n d was 1. 6 3  ±  0. 7 1 
at 1 2 m o nt hs. O verall, B C V A s h o we d a tre n d t o w ar ds i m pr o ve me nt b ut di d n ot reac h 

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statistical si g nifica nce. After t hree m o nt hs, t he B C V A a p peare d t o re gress t o war ds 
pre o perati ve le vels. T h e a vera g e ce ntral s u bfiel d f o veal t hic k ness a p peare d t o decrease after 
s ur ger y at all ti me p oi nts. Total mac ular v ol u me si g nifica ntl y decrease d fr o m b aseli ne le vels 
at si x m o nt hs. O nl y t w o of 1 1 e yes h a d a n el e vati o n of I O P a b o v e 2 1 m m H g at a n y 
p ost o perati ve visit be y o n d o ne wee k, b ot h e yes reac hi n g a n I O P of 2 4  m m H g a n d 
res ol vi n g  wit h o ut treat me nt. Of t he si x e yes t hat w ere p ha ki c at bas eli ne, o n e e ye wit h a pre -
e xisti n g gra de 2 + n u clear scler otic cataract de vel o pe d a 1 + p osteri or s u bca ps ular cataract 
d uri n g t he f oll o w -u p peri o d.  
Tetz a n d c o -w or k ers (Tet z, Rizz o, a n d A u g usti n 2 0 1 2 ) i n vesti gate d t he s u prac h or oi d al 
a d mi nistrati o n of a c o m bi nati o n of be vaciz u m a b a n d tria mci n ol o ne t o t he s u b mac ular 
s u prac h or oi dal s p ace, vi a a micr ocat h eter, i n e yes wit h a d va nce d n e o vasc ul ar A M D t hat faile d 
t o res p o n d t o c o n ve nti o n al t hera p y. A sli g ht i m pr o ve me nt i n t he a vera ge B C V A at o ne m o nt h 
a n d si x m o nt hs was  o bser ve d, b ut statistical si g nifica nce  was n ot reac h e d  at a n y ti me 
p oi nt c o m pare d wit h bas eli ne.  I nitial ce ntral s u bfiel d f o veal t hic k ness  was 
4 0 7. 2  μ m ( S D = 2 2 9. 8), decreasi n g at o ne m o nt h t o 3 3 3. 3  μ m ( S D = 1 7 9. 4), re mai ni n g sta ble at 
t hree m o nt hs a n d tre n di n g t o war ds i nitial le vels at si x m o nt hs ( 3 8 4. 8 μ m, S D = 2 6 5. 7).  
N o seri o us c o m plicati o ns  were e nc o u ntere d d uri n g t he a d mi nistrati o n of t hera p y.   O nl y o ne  of 
2 1 e yes i ncl u de d i n t he st u d y e x perie n ce d a tra nsie nt ele vati o n i n I O P at t hree m o nt hs, w hic h 
was me dicall y c o ntr olle d. I n t w o e yes, a n i n crease i n n uclear scl er ot ic cataracts  was n ote d. 
Rizz o a n d c o -w or kers (Rizz o et al., 2 0 1 2 ) e v al uat e d 6 e yes wit h r eti nal vei n occl usi o n or 
diff use D M E acc o m pa ni e d b y massi ve s u bf o veal  har d e x u dat es t hat were u nres p o nsi ve t o 
m ulti ple I V T i njecti o ns. T he e yes u n d er we nt a si n gle treat me nt i n w hic h a c o m bi nati o n of 
be vaciz u m a b a n d tria mci n ol o ne were  a d mi nistere d t o t he s u b mac ular s u prac h or oi dal s pace via 
a micr ocat h eter. B C V A i m pr o ve d b y 2 + li nes  o n a rea di n g c hart  i n 4 e yes a n d re mai ne d sta ble 
i n 2 e yes. At 1 t o 2 m o nt hs, t he har d e x u d ates ha d al m ost c o m pletel y res ol ve d i n all e yes. N o 
c o m plicati o ns were o bs er ve d.  
I n c o m passi o nate use p atie nts i n S witzerla n d, O x ul u mis®  was use d t o deli ver 2. 4 m g t o 4 m g 
Triese nce ®  i n a t otal of 5  patie nts wit h 9  treat me nts (i ncl u di n g 3 re peat treat me nts a n d 1 
bilateral treat me nt ) wit h refract or y mac ular e de m a, m ostl y p ost -s ur gical c yst oi d mac ular 
e de ma. T h ese patie nts s h o we d, i n c o ntrast t o t heir pretreat me nt, after s u prac h or oi dal 
a d mi nistrati o n of T A, g o o d a nat o mical res p o ns e wit h a q uic k o nset, as well as vis ual 

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i m pr o ve me nts. N o de vic e-rel ate d A Es a n d n o c h alle n ges wit h I O P rises after T A 
a d mi nistrati o n were des cri be d (f or details see I n vesti gat or ’s Br oc h ure).  
2. 3  
N o ncli nic al e x perie nces wit h D M A micr os p heres i n t he s u pr ac h or oi d al s p ace  
W hile t here is n o  a ni mal m o del c o veri n g precli nical ly all rele va nt as p ects of cli nical 
s u prac h or oi dal D M E treat me nt, s o me as pects of D M E s uc h as reti nal i nfla m mati o n or V E G F -
dri ve n vasc ular per m ea bilit y  ca n be st u die d i n ac ute a ni mal m o dels.  
T he e xte nt of p h ar mac o d y na mic ( P D) effects of preli mi nar y micr os p here f or m ulati o ns ha ve 
bee n esti mate d d uri n g pri mar y P D st u dies usi n g a h u ma n -V E G F i n d uce d reti nal vasc ular 
h y per per m ea bilit y m o del i n ra b bits. T he effect of t he dr u g has bee n  assess e d usi n g 
fl u or o p h ot o metr y or fl u orescei n a n gi o gra p h y. De x a met has o ne acetat e micr os p heres (i n 
vari o us s p here si zes, p ol y mer c o m p ositi o n , a n d d oses) a d mi nistere d s u prac h or oi dall y were 
c o m pare d t o i ntra vitreal Oz ur de x ®  at 1 4, 4 2, a n d u p t o 6 0 da ys. T he use of earl y f or m ulati o ns 
a n d a s ur gical c o m p o ne nt t o t he s u prac h or oi dal a d mi nistrati o n , differe nt fr o m t he fi nal 
O x ul u mis ®  desi g n a n d pr oce d ure, i n ra b bits d uri n g earl y de v el o p me nt le d t o hi g h varia bilit y 
bet wee n t hes e  st u dies. Ne vert heless, a tre n d f or i n creas e d d ura bilit y of effect vers us Oz ur de x ®  
was o bser v e d , a n d res ults s u p p ort t hat micr os p here f or m ulati o ns are well t olerate d w h e n 
a d mi nistere d s u prac h or oi dall y a n d res ult i n deli ver y of ster oi ds c o m para ble t o e xisti n g ster oi d 
me dicati o ns  c urre ntl y use d cli nicall y f or t he tr eat me nt of e ye dise ases  wit h a nee d f or a nti -
e de ma a n d a nti -i nfla m mat or y acti vit y. 
D e xa met has o n e ( D X M ) a n d D M A c o nce ntrati o ns i n c h or oi d, reti na, vitre o us h u m or, a q ue o us 
h u m or , a n d le ns tiss ues ha ve bee n e val u ate d usi n g a vali date d bi oa n al ytical met h o d i n 
p har mac o ki netic ( P K) st u dies i n ra b bits f or 1 2 0 d a ys a n d 2 2 0 da ys. T w o of t he st u dies 
c o m pare d a si n gle a d mi nistrati o n of D M A micr os p heres utilizi n g differe nt releas e rates a n d 
d oses a d mi nistere d i n t he s u prac h or oi d al s pace v ers us a si n gle Oz ur de x ®  i ntra vitreal 
a d mi nistrati o n  (all o metric 0. 3 5 m g  d ose) . T he st u dies de m o nstrate d c o m para ble dr u g le vels i n 
t he c h or oi d a n d reti na a n d l o wer le vels i n a nteri or tiss ues vers us Oz ur de x® . O ne of t he O x ul ar 
f or m ulati o ns ( 1 7 0 µ g D M A) i n t he first P K st u d y a n d t w o ( 1 6 5 5 µ g D M A a n d 9 6 0  µ g D M A) 
i n t he sec o n d P K  st u d y mai ntai ne d detecta bl e c h or oi d a n d reti nal dr u g le vels, res pecti vel y, 
t hr o u g h t he 1 2 0 da ys, wh ereas D X M  le vels f oll o wi n g Oz ur de x®  a d mi nistrati o n were n ot 
mai ntai ne d after da y 6 0 i n kee pi n g wit h p u blis he d data. I n  a t hir d P K st u d y, w hic h was a 
f or mal G L P p har m ac o ki netic st u d y brac k eti n g rel ease rates a n d d os es of 4 differe nt 
f or m ulati o ns of micr os p h eres (a si n gle d ose of 6 0 0  µ g t o 1 5 5 0 µ g D M A) i nte n de d t o be use d 

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i n G L P t o xic ol o g y st u dies a n d f or t he sel ecti o n of t he P hase 2 cli nical st u dy’s  f or m ulati o n, 
distri b uti o n t o c o m part me nts of t he e ye was si milar f or all treat me nts. T he hi g hest 
c o nce ntr ati o n was o bser v e d i n t he c h or oi d a n d t he l o west c o nce ntr ati o n was o bser ve d i n t he 
le ns a n d i n t he vitre o us, w hate ver t h e treat me nt a n d f or b ot h D X M a n d D M A. I n all e ye 
str uct ures, t he c o n ce ntr ati o ns of DX M were l o wer t ha n t he c o nce ntrati o n of D M A. I n plas ma, 
D X M a n d D M A were q u a ntifia ble ( > L L O Q) o nl y i n fe w sa m ples, de m o nstr ati n g a ver y l o w 
s yste mic a bs or pti o n of t he D X M a n d D M A. 
F or f urt her det ails of t he n o ncli nical st u dies, refer t o t he I n vesti gat or ’s Br oc h ure.  
Base d o n t hese n o ncli nic al p har mac o d y n a mics a n d p har mac o ki netics d ata o n O X U -0 0 1 as 
well as pri or cli nical d ata f or s u prac h or oi dal deli v er y of ster oi ds, we e x p ect t he precli nical P K 
a n d t o xic ol o g y fi n di n gs of O X U -0 0 1 t o tra nslate t o a better safet y pr ofile  wit h res pect t o 
e x p os ure of a nteri or s e g me nts of t he e ye a n d I O P a n d i ncrease a n d a mea ni n gf ull y l o n ger 
d ura bilit y pr ofile c o m pare d t o Oz ur de x ® . 
2. 4  
Be nefit/ Ris k Assess me nt  
T his st u d y is t he first cli nical trial t o assess s u prac h or oi dal O X U -0 0 1, li miti n g t he a bilit y t o 
deli neate t he  cli nic al be n efit/ris k pr ofile.  Cli nical e x perie n ce  ori gi nates fr o m  t he use of t he 
O x ul u mis ®  t o a d mi nister Triese nce® (tria mci n ol o n e acet o ni de) i n c o m passi o nate use i n 
patie nts wit h mac ular e d e ma of differe nt eti ol o gies i n dicates vis ual a n d a nat o mical 
i m pr o ve me nt a n d fr o m a cli nical trial i n D M E ( O X U C T-1 0 3, C A P E, N C T 0 5 5 1 2 9 6 2 ). No 
se vere, s eri o us a d v erse e ve nts or a d verse de vice effects ha ve bee n re p orte d  s o far. I n t he 
C A P E trial, t o -date, t he use of t he O x ul u mis ®  t o a d mi nister Triese nce t o t h e s u prac h or oi dal 
s pace wit h v ol u mes of u p t o 1 0 0 µl i n trial s u bjects wit h D M E has bee n well t olerate d. 
Treat me nt -e mer ge nt oc ul ar a d verse e v e nts ( A Es) were g e nerall y of mil d t o m o derate i nte nsit y 
a n d of li mite d d urati o n. N o tre at me nt -relate d n o n-oc ular A Es w ere o bs er ve d. N o seri o us 
a d verse e ve nts ( S A Es) or seri o us u ne x pecte d a d verse reacti o ns ( S U S A Rs) ha ve bee n 
o bser ve d. O n e ( 1) a d vers e e ve nt of s p ecial i nterest ( A E SI; se vere oc ular pai n of li mite d 
d urati o n) has bee n o bser ve d i n a s u bject r ecei vi n g 1 0 0 µl st u d y treat me nt.  
Precli nical data fr o m ra b bits als o i n dicate l o w e x p os ure of t he le ns a n d a nteri or c ha m ber 
c o m p o ne nts t o de xa met h as o ne w he n tr eate d wit h s u prac h or oi dal O X U -0 0 1 , a n d str o n g a nti-
e de ma a n d a nti -i nfla m mat or y effects. T he pri nci pal e x pectati o ns of t hera pe utic effects wit h 
O X U -0 0 1 , t heref ore, b uil d o n t he a m ple a n d deca d e -l o n g e x perie nce wit h i ntra oc ular ster oi ds, 

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i ncl u di n g Oz ur de x®  (B o yer et al., 2 0 1 4 ), a n d rece ntl y s u prac h or oi dal tria mci n ol o ne acet o ni de  
(Ye h et al., 2 0 2 0 ). 
T he s u prac h or oi dal a d mi nistrati o n pr oce d ure of O X U -0 0 1, i n c o ntrast t o I V T i njecti o n 
reac h es m ore p osteri or p arts of t he reti na, t o war ds t he mac ula, t hr o u g h t he s u prac h or oi dal 
s pace. T h e s u prac h or oi dal r o ute of a d mi nistrati o n is, t heref ore, e x p ecte d t o res ult i n fa v ora ble 
safet y a n d t olera bilit y, partic ularl y re g ar di n g c o m plicati o ns, s uc h as i ncreas e d I O P a n d 
cataract f or m ati o n i n a d diti o n t o p ote ntial i m pr o ve me nt i n efficac y d ue t o t h e e x pecte d hi g her 
e x p os ure of de xa met has o ne i n t he reti na a n d c h or oi d.  
O X U -0 0 1 use d i n t he c urre nt st u d y is e x pecte d t o satisf y a n u n met me dical nee d t o:  
1.  
Re d uce t he ris k of ster oi d -i n d uce d c o m plicati o ns a n d a d verse e v e nts  
2.  
Pr ol o n g a n d s ustai n  t he efficac y of ster oi d treat me nt i n D M E  
3.  
E n ha nce  t he effi cac y of ster oi d treat me nt i n D M E  
T he oretical ris ks ass ociat e d wit h t he s u prac h or oi dal deli ver y pr oce d ure s i ncl u de 
e n d o p ht hal mitis, c h or oi dal he m orr ha g e, c h or oi d al eff usi o n, reti nal pe netr ati o n , a n d reti nal 
detac h me nt, a m o n gst ot h ers. I n a d diti o n, t he eli gi bilit y criteria of t his trial e xcl u de s u bjects 
wit h str uct ural lesi o ns of t he e ye w all ( e. g., s u bjects wit h scleral ect asia or s cleral defect, 
w hic h ma y ha ve a ris k of scleral perf orati o n) w hic h f urt her re d uces a n y p ot e ntial pr oce d ural 
ris ks. T his ris k ha s s o far n ot bee n o bser ve d as A Es in 9  s u bjects i n c o m passi o nate use a n d i n 
2 0 treate d s u bjects i n t he o n g oi n g C A P E trial ( O X U C T-1 0 3, C A P E, N C T 0 5 5 1 2 9 6 2 ). Oc ular 
A Es o bser ve d  wit h t he O x ul u mis ®  de vice i ncl u de e x pecte d e ve nts f or t h e t y pe of treat me nt 
a n d dr u g a d mi nistere d i n cl u di n g s u bc o nj u ncti val he m orr ha g e, i na d vert e nt i ntra vitreal dr u g 
de p osit, i nc o m plete d ose a d mi nistrati o n, n o n -c o m pleti o n of t he st u d y pr oce d ure, a n d oc ul ar 
pai n a n d /or disc o mf ort.  
To i m me diatel y bec o me a ware of  t he occ urre nce of n o vel p ote ntial ris ks, i n t he O X U -0 0 1 
pr o gra m re p orti n g of A d verse E ve nts of S pecial I nterest has bee n defi n e d  i n Secti o n 9. 5. 6 . 
T he f oll o wi n g feat ures of t he O x ul u mis ®  ma y miti gate a n d li mit t he p ote ntial ris k of a d verse 
e ve nts wit h s u prac h or oi dal o p ht hal mic a d mi nistrati o n:  
1.  
T he atra u m atic , fle xi ble desi g n of t he micr ocat het er  
2.  
T he r o u n de d b all -li ke cat heter ti p 
3.  
T he c o ntr ol o ver t h e s pee d of deli ver y b y a dj ust me nt of t he O x ul u mis ®  de vice  

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4.  
T he 1 5 -2 0° ta n ge ntial i ns erti o n of O x ul u mis ®  is relati ve t o t he s urface of t h e e ye. 
S tee per a n gles of a p pr oac h ma y o nl y be necessar y wit h i nitial e n ga ge me nt of t he 
i nserti o n nee dle. U si n g a n a n gle of a p pr oac h of 4 5° a n d m or e t o t he sclera t hr o u g h o ut 
t he pr oce d ure ma y b e  ass ociate d wit h a n i ncrease d  ris k of pe netr ati o n of t he vitre o us 
ca vit y). 
Still, as t he O x ul u mis ®  pr oce d ure is relati vel y n o v el, n o n -c o m pleti o n of micr ocat h eter 
place me nt ma y ha p pe n i n a n i n -cli nic setti n g, re q uiri n g t he use of a pr oce d ural varia nt t hat 
uses a n i ncisi o n of t he c o nj u ncti va a n d/ or te n o n t o i ncreas e visi bilit y of t he scleral 
e n ga ge me nt i n t he i nserti o n p hase of t he O x ul u mis ®  pr oce d ure.  To facilitate t he decisi o n o n 
t he i nitial setti n g f or t he st u d y pr oce d ure, t he treati n g p h ysicia n ( u n mas ke d i n vesti gat or i n 
Part B) will assess t he e x pecte d pr o ce d ural c o m pl e xit y as l o w, me di u m, or hi g h. To  assist t his 
assess me nt, a g ui da nce d oc u me nt is i ncl u de d as p art of t his pr ot oc ol, w hic h me nti o ns as pects 
t o c o nsi der f or t he o v erall e x pert j u d g me nt o n c o m ple xit y (see Secti o n 1 2. 4 ) Inf or mati o n 
a b o ut t he k n o w n a n d e x p ecte d be n efits a n d ris ks a n d p ote ntial  a d verse e ve nts ( A Es) of  
O X U -0 0 1 ca n be f o u n d i n t he In vesti gat or’s B r oc h ure (I B) Refere nce Safet y I nf or mati o n . As 
t here ha v e bee n s o far n o S A Es o bser ve d f or t h e O x ul u mis® , at t he start of O X U C T-1 0 2 n o 
seri o us a d vers e reacti o ns ( S A R) ca n be d efi ne d a n d t he list of A E SI defi ne d f or t he O X U-0 0 1 
pr o gra m is base d o n t he oretical c o nsi derati o ns.  
B e nefits ass ociate d wit h Oz ur de x ®  a d mi nistrati o n i ncl u de t he p ote ntial D M E res ol uti o n ( i.e., 
i m pr o ve d B C V A a n d n or malizati o n of reti nal t hic k ness) as s u m marize d i n a rece nt cli nical 
re vie w (Ritti p hair oj et al., 2 0 2 0 ). Ris ks ass ociate d wit h I V T Oz ur de x ®  a d mi nistrati o n i ncl u de 
cataract de v el o p me nt or deteri orati o n ( 6 8 %), I O P ele vati o n ( 2 8 % at least 1 0 m m H g, 1 5 % at 
least 3 0 m m g H g), a n d e n d o p ht hal mitis ( <2 % ). M ore details a b o ut t he a d verse reacti o ns 
ass ociate d wit h I V T Oz ur de x ®  ca n b e f o u n d  i n re g ulat or y d oc u me nts as a p plica ble f or t he 
res pecti ve tri al c o u ntries ( U S, E U, Israel). It is i m p orta nt t o n ote t hat cataract pr o gressi o n is 
s pecificall y o bser ve d wit h re peat a n d l o n g -ter m O z ur de x®  treat me nt (B o yer et al., 2 0 1 4 ). I n 
t he M E A D 3-year st u d y of Oz ur de x ® , cataract pr o gressi o n was m ostl y see n after m o nt h 1 2 
a n d o ver 7 5 % of t he catarac t s ur g eries wit h Oz ur de x ®  were p erf or me d bet wee n m o nt h 1 8 a n d 
3 0. S o  t he ris k wit h a p ote ntial si n gle a d mi nistrati o n of Oz ur de x ®  i n Part B treat me nt ar m B 3 
i n t he c urre nt trial a p pears j ustifie d t o ha ve a ra n d o mize d, mas ke d hea d-t o-hea d c o m paris o n 
of  O X U -0 0 1 a n d Oz ur de x ® . I n a d diti o n, le ns o pacit y will be ti g htl y m o nit ore d  at all st u d y 
visits wit h t he slit la m p e xa m.  

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Pa ge 5 4  of  1 6 9  
As part of t he ris k miti gati o n strate g y, t he st u d y will i ncl u de t w o parts, Part A a n d Part B. 
Part  A will i ncl u de  ei g htee n ( 1 8) D M E s u bjects, tr eat me nt-naï ve or pre vi o usl y treate d wit h 
I V T a nti-V E G F t hera pies . S u bjects will be ra n d o mize d t o o ne of t w o  d ose  l e vels of O X U -
0 0 1, a 1. 5 m g mi d -d ose a n d a 3. 0 m g  hi g h d ose,  i n a 1: 1 fas hi o n wit h a p pr o xi matel y  9 s u bjects 
i n eac h d ose gr o u p. After t he last s u bject treate d i n Part A has reac he d t h e Wee k 6 visit, a 
safet y re vi e w will occ ur wit h f oc us o n earl y a n d pr oce d ural ris ks, a n d t he c ha n ge i n I O P 
t hr o u g h o ut t he peri o d of o bser vati o n. T he st u d y D M C , base d o n a re vi e w of t he  Wee k 6 
safet y, will gi ve a rec o m me n dati o n f or t he start of Part B , i ncl u di n g a rec o m me n dati o n if t he 
1. 5 m g a n d 3. 0 m g O X U -0 0 1 s h o ul d be teste d i n Part B.  
T he f ores ee n D os es i n Part B are D ose 1 i n ar m B 1 ( D M A 1. 5 m g, mi d -d ose) a n d D os e 2 i n 
ar m B 2. D ose 2 is i nte n de d t o be O X U 0 0 1 D M A 3. 0 m g. In case of p ote ntial safet y c o ncer ns 
wit h e. g., earl y si g nifica nt I O P i ncreas e i n t he A 2 ar m wit h  3. 0 m g t hr o u g h Wee k 6, ar m B 2 
will  use 0. 7 5 m g  O X U -0 0 1 as  D ose 2.  
T he ra n d o mizati o n sc he me is 2: 2: 1 wit h Ar m B 3, t he Oz ur de x ®  ar m i ncl u di n g o nl y half t he 
n u m ber of s u bjects c o m p are d t o t he O X U -0 0 1 Ar ms B 1 a n d B 2, t o o pti mize t he n u m ber of 
s u bjects o n Oz ur de x ® . 
To detect a d v erse e ve nts a n d ot her u nf oresee n ris ks a n d t o p ote ntiall y i nitiate 
c o u nter meas ures i n a ti m el y fas hi o n, s u bjects will be m o nit ore d cl osel y f or  6 0  mi n utes after 
a d mi nistrati o n of O X U -0 0 1 t o t he s u prac h or oi dal s pace. T his m o nit ori n g i ncl u des 
o p ht hal m osc o p y a n d at least t w o I O P meas ure me nts.  M o nit ori n g ti mes l o n ger t he 6 0 mi n utes 
ma y be re q uir e d t o o bser ve n or malizati o n of t he I O P p ost treat me nt.  A p ost -a d mi nistrati o n 
o p ht hal mic e xa m a n d I O P meas ure me nts will als o be perf or me d after t he a d mi nistrati o n of 
Oz ur de x ® . A d diti o nall y, visits f oll o wi n g treat me nt, o n da y 1, wee k 1, wee k 4, wee k 6  
( ma n dat or y i n Part A, o pti o nal i n Part B), wee k 8, a n d e ver y 4 wee ks t h ereafter, will i ncl u de 
m ulti ple safet y e val uati o ns t o e ns ure t he detecti o n a n d ma na ge m e nt of a n y e mer gi n g a d verse 
e ve nts. Q uesti o n naires t o i n vesti gat or a n d s u bject  i nter vie ws will assess det ails of perf or mi n g 
t he O x ul u mis pr oce d ure a n d pai n a n d disc o mf ort. 
Ta ki n g i nt o acc o u nt t he meas ures use d t o mi ni mize ris k t o s u bjects i n t his st u d y, t he p ote ntial 
ris ks i de ntifie d i n ass ociati o n wit h O X U-0 0 1 are j ustifie d b y t he a ntici pate d be nefits t hat ma y 
be aff or de d t o s u bje cts wit h D M E.  

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Pa ge 5 7  of  1 6 9  
•  de vice a d v erse effects 
(seri o us a d verse de vi ce 
effects a n d treat me nt -
e mer ge nt n o n -s eri o us 
a d verse d e vice effects ) 
E x pl or at or y  
1.  
T o e val uate t he d ura bilit y of 
s u prac h or oi dal O X U-0 0 1 i n 
s u bjects wit h D M E. 
2.  
T o e x pl ore t he efficac y of 
s u prac h or oi dal O X U-0 0 1 
deter mi ne d b y c h a n ge i n 
vis ual ac uit y, e de ma c o ntr ol, 
a n d i m pact o n visi o n -relate d 
q ualit y of life i n s u bjects wit h 
D M E . 
 
1.  Ti me t o s u bjects re q uiri n g 
f oll o w-o n treat me nt.  
2.  Mea n C ha n ge B C V A ( E T D R S) 
at Wee k 2 4 c o m pare d t o 
baseli ne.  
3.  Mea n C ha n ge i n ce ntral 
s u bfiel d t hic k ness ( S D-O C T) at 
Wee k 2 4 c o m pare d t o b aseli ne.  
4.  Mea n C ha n ge i n B C V A 
( E T D R S) t hr o u g h Wee k 5 2 
c o m pare d t o bas eli ne.  
5.  Mea n C ha n ge i n ce ntral 
s u bfiel d t hic k ness t hr o u g h 
Wee k 5 2 c o m pare d t o b aseli ne.  
6.  Pr o p orti o n of s u bjects re q uiri n g 
f oll o w-o n treat me nt at st u d y 
visits fr o m Wee k 1 2 t hr o u g h 
Wee k 5 2.  
7.  Pr o p orti o n of s u bjects wit h 5 -, 
1 0 -, or 1 5-letter ( E T D R S) gai n 
of B C V A fr o m wee k 4 t o wee k 
5 2 c o m pare d t o bas eli ne.  
8.  Pr o p orti o n of s u bjects wit h 5 -, 
1 0 -, or 1 5-letter ( E T D R S) l oss 
of B C V A fr o m wee k 4 t o wee k 
5 2 c o m pare d t o bas eli ne.  
9.  Pr o p orti o n of s u bjects wit h 
B C V A  > 6 8  letters ( E T D R S) at 

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O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 5 8  of  1 6 9  
eac h st u d y visit fr o m wee k 4 t o 
wee k 5 2.  
1 0.  Mea n c ha n g e i n N EI V F Q -2 5 
T otal Sc ore at Wee k 2 4, a n d 
Wee k  5 2 c o m pare d t o b aseli ne.  
F or all efficac y e n d p oi nts, t he pre-tr eat me nt assess me nts o n t he baseli ne visit V 2, Da y 0, will 
be c o nsi dere d t he baseli n e val ues f or t h e c o m paris o n of p ost -treat me nt val u es. T he m ost 
rece nt b aseli ne ass ess me nts  of V 2  pri or t o treat me nt will be c o nsi dere d t he baseli ne val ue i n 
case a n y re p eat assess me nts ha p pe n d uri n g V 2 acti vities . 
T he o bjecti ves f or e val u ati n g t he de vice safet y a n d perf or ma n ce are s e parat el y o utli ne d i n t he 
latest versi o n of t he O x ul u mis®  Cli nical E val uati o n Pla n ( C E P) Versi o n O X U C T -1 0 2.  
3. 2  
Esti m a n ds  
F or t he o bjecti ve of t his cli nical trial c urre ntl y , n o esti ma n d is defi ne d. Dat a ge nerate d i n t his 
cli nical trial i n treat me nt -naï ve  or  pre vi o usl y treate d D M E s u bjects f or patie nt-rele va nt 
o utc o mes li ke B C V A a n d disease -relate d o utc o m es li ke meas ure me nts of m ac ular e de ma will 
i nf or m esti ma n ds f or s u bse q ue nt cli nical trials. Als o, cli nical e x peri e nce wit h t he O x ul u mis®  
o p ht hal mic pr oce d ure will c o ntri b ute t o b uil di n g esti ma n ds f or f ut ure trials of O X U -0 0 1.  
4  
St u d y Desi g n  
4. 1  
O ver all Desi g n  
T he st u d y p o p ulati o n will c o nsist of a p pr o xi matel y 1 2 8  a d ult fe male or m ale s u bjects wit h 
D M E wit h a p pr o xi matel y 1 8 s u bjects treate d i n P art A a n d a p pr o xi matel y 1 1 0 s u bjects treat e d 
i n Part B t hat: 
1.  
Ha ve bee n dia g n ose d wit h T y pe 1 or T y pe 2 dia betes mellit us.  
2.  
Ha ve D M E i n v ol vi n g t he ce nter of t he f o vea wit h ce ntral s u bfiel d t hic k n ess ( C S T) i n 
t he st u d y e ye at t he scree ni n g visit, c o nfir me d b y t he C R C, of at least 3 2 0 µ m o n S D 
O C T ( meas ur e me nt fr o m R P E t o I L M, i ncl usi vel y). 
3.  
Ha ve B C V A bet w ee n 3 4 a n d 7 8  letters ( usi n g a n E T D R S c hart, a p pr o xi mat e S nelle n 
ac uit y of 2 0/ 2 0 0 – 2 0/ 3 2) i n t he st u d y e ye.  
4.  
Are treat me nt-naï ve  or pre vi o usl y treate d wit h I V T a nti-V E G F i n t he st u d y e ye. 

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C O N FI D E N TI A L  
Pa ge 5 9  of  1 6 9  
O nl y o ne ( 1) e y e will be deter mi ne d as t he st u d y e ye a n d o nl y t he st u d y e ye will recei ve a 
si n gle a d mi nistrati o n of st u d y treat me nt o n Visit 2, Da y 0. St u d y e yes nee d t o meet all 
i ncl usi o n criteria a n d n o n e of t he e x cl usi o n criteria. If b ot h e yes me et t he rel e va nt criteria, t he 
e ye wit h t he w ors e B C V A will be selecte d as t he st u d y e ye; if b ot h e yes m eet t he rel e va nt 
criteria a n d ha ve t he s a m e B C V A, t he i n vesti gat or ca n select t he st u d y e ye.  
If o ne e y e is previ o usl y treate d (f or all o we d pri or treat me nt see Secti o n 5. 2  a n d Secti o n 7. 8. 1 ), 
t he ot her e ye m a y still q ualif y as a treat me nt -naï ve st u d y e ye if all i ncl usi o n criteria a n d n o ne 
of t he e xcl usi o n criteria are met.  
T he s u bjects’ fell o w e y e ma y c o nti n ue t o recei ve treat me nt f oll o wi n g g ui deli nes a n d 
sta n dar ds at t he i n vesti gati o nal site. S u bjects i n Part A s h o ul d n ot recei ve st er oi d treat me nt i n 
t heir fell o w e y e, as t his ma y ha ve a n i m pact o n t he P K assess me nt of t he st u d y treat me nt. 
Treat me nt of t he fell o w e ye is n ot c o nsi dere d part of t he st u d y treat me nt.  
T he st u d y has t w o parts ( Part A a n d Part B) . It will i ncl u de b ot h s u bjects t hat are treat me nt-
naï ve a n d s u bjects t hat h a ve bee n pre vi o usl y treate d wit h a nti -V E G F t hera p ies. 
Part A is t he o pe n -la bel p art of t he st u d y c o m p ose d of t w o ( 2) parallel , treat me nt ar ms 
ra n d o mize d i n a 1: 1 sc h e me a n d will i ncl u de a p pr o xi matel y 1 8 s u bjects.  N o mi ni m u m 
n u m ber of treat me nt -naï v e s u bjects is fi xe d i n Part A.  
Ta ble 6  P art A Tre at me nt Ar ms, I nter ve nti o ns, a n d N u m ber of S u bjects  
Tre at me nt 
Ar m  
I nter ve nti o n 
S u bjects  
A 1  
O ne  ( 1) tr eat me nt wit h s u prac h or oi d al 
  
mi d d ose (D M A  1. 5 m g)  O X U -0 0 1  
N = 9  
A 2  
O ne ( 1) tr eat me nt wit h s u prac h or oi d al 
  
hi g h d ose ( D M A 3. 0 m g) O X U -0 0 1  
N = 9  
Part B is t he mas ke d, ra n d o mize d, c o ntr olle d part of t he st u d y. T his part is c o m p ose d of t hree 
( 3) parallel  ar ms ra n d o mize d i n a 2: 2: 1 sc he me as f oll o ws:  
Ta ble 7  P art B Tre at me nt Ar ms, I nter ve nti o ns, a n d N u m ber of S u bjects  
Tre at me nt 
Ar m  
I nter ve nti o n 
S u bjects  
B 1  
O ne ( 1) tr eat me nt wit h  s u prac h or oi d al 
 
D ose 1 ( mi d d ose D M A 1 . 5 m g) O X U-0 0 1  
n = 4 4  

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C O N FI D E N TI A L  
Pa ge 6 0  of  1 6 9  
B 2  
O ne ( 1) tr eat me nt wit h  s u prac h or oi d al 
 
D ose 2 (t bc. D M A 3. 0 m g or 0. 7 5 m g ; 
 
d ose base d o n t he o utc o me of Part A 6 wee ks) O X U -0 0 1  
n = 4 4  
B 3  
O ne ( 1) tr eat me nt wit h  
 
i ntra vitreal Oz ur de x®  ( de xa met has o ne 0. 7 m g ) 
n  = 2 2  
I n Part B, a t otal of 1 1 0  s u bjects, w h o are treat me nt-naï ve or pre vi o usl y  a nti-V E G F treate d (i n 
t he st u d y e ye) will be treate d. E nr oll me nt of pre vi o usl y treate d a n d tr eat me nt -naï ve s u bjects 
will be c o m petiti ve, wit h at least 5 5 s u bjects bei n g treat me nt -naï ve i n t he st u d y e ye. 
E nr oll me nt of s u bjects t hat are a nti -V E G F pre vi o usl y treate d i n t he st u d y e ye will st o p o nce 
5 5 s u bjects wit h pre vi o us a nti -V E G F treat me nt i n t he st u d y e ye are ra n d o mize d t o all o w 
reac hi n g t he f ores ee n n u m ber of treat me nt-naï ve s u bjects.  S u bjects will be stratifie d base d o n 
t heir a nti-V E G F treat me nt hist or y.  
I n t his trial t he a d mi nistrati o n of O X U-0 0 1 wit h t he O x ul u mis ill u mi nate d micr ocat heter  will 
be perf or me d wit h t w o differe nt pr oce d ural varia nts de pe n di n g o n s u bject c haract eristics a n d 
pr oce d ural s uccess:  
•  Sta n dar d  Vari a nt : A d mi nistrati o n wit h t he O x ul u mis® de vice wit h o ut a n i ncisi o n of 
t he c o nj u ncti va/te n o ns. T he sta n dar d varia nt ca n b e perf or me d i n a n y setti n g, i.e., i n-
cli nic, i n a pr oce d ure r o o m or i n a n o perati n g r o o m.  
•  C o njI ncisi o n  Varia nt : I ncisi o n of t he c o nj u ncti va/te n o ns at t he start of t he O X U-0 0 1 
a d mi nistrati o n t o i ncreas e visi bilit y a n d access f or t he scleral e n ga ge me nt p hase of t he 
O X U -0 0 1 a d mi nistrati o n. T he i ncisi o n o pe ni n g of t he c o nj u ncti va/te n o ns n ee ds t o be 
cl ose d b y usi n g sta n dar d s ur gical tec h ni q ues a n d material ( e. g., fi bri n gl ue, s ut uri n g 
material): T his varia nt ca n be use d at t he discreti o n of t he treati n g p h ysicia n eit her a) 
i nitiall y if s u bject c haract eristics a n d/ or me dical hist or y s u g gest t his varia nt, or b) if 
wit h t he Sta n dar d O X U -0 0 1 a d mi nistrati o n varia nt, st u d y treat me nt ca n n ot be 
a d mi nistere d.  
T he C o njI ncisi o n O X U -0 0 1 Varia nt ca n o nl y be perf or me d i n a s ufficie ntl y e q ui p pe d 
e n vir o n me nt f or o pe ni n g a n d cl osi n g t he c o nj u ncti va/te n o ns. A n a d e q uate pr oce d ural 
setti n g, tec h ni q ues a n d m aterial uses f oll o ws t he s ur gical sta n dar d i n t he res pecti ve 
ge o gr a p hic re gi o n ( i.e., a n a de q uatel y e q ui p pe d pr oce d ure r o o m or a n o p erati n g 
r o o m). 

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C O N FI D E N TI A L  
Pa ge 6 1  of  1 6 9  
T he treati n g p h ysicia n will deter mi ne at t he scree ni n g visit ( V 1), if i nitiall y t he Sta n dar d 
Varia nt or t he C o njI n cisi o n Varia nt will be use d i n a res pecti ve s u bject. T h e baseli ne visit 
acti vities will be pla n ne d acc or di n gl y wit h t hree differe nt s c he d ules f or bas eli ne visit 
activities:  
•  O X U -0 0 1 Sta n dar d Vari a nt  wit h o ut  s ur gical i ncisi o n is t y picall y perf or me d i n a n 
i n-cli nic or pr oce d ure r o o m setti n g  
•  O X U -0 0 1 C o njI ncisi o n Varia nt  wit h c o nj u ncti va/te n o ns i ncisi o n is t y picall y 
perf or me d i n a s ur gicall y e q ui p pe d pr oce d ure or a n o perati n g r o o m  
•  S witc h fr o m O X U -0 0 1 Sta n dar d t o C o njI n cisi o n Varia nt . I n t his sce n ari o 
pr oce d ural atte m pts are t y picall y starte d i n -cli nic. If t he O X U -0 0 1 Sta n dar d 
Varia nt c a n n ot be c o m pl ete d, t he pr oce d ure is s witc he d t o t he C o njI n cisi o n 
Varia nt a n d d e pe n di n g o n t he facilit y will t he n be eit her perf or me d i n t he s a me 
facilit y (s ur gicall y e q ui p pe d pr oce d ure r o o m) or h as t o be resc h e d ule d i n a s ur gical 
facilit y, w hic h ma y be dista nt t o t he c ore i n vesti gati o nal site 
T he ma xi m u m ti me i nter val t o c o m plete all baseli ne visit acti vities is 1 4  da ys i ncl u di n g 
p ote ntial resc he d uli n g of treat me nts i n case s witc h of t he pr oce d ural varia nts is nee de d.  
I n Part B, if a treati n g p hysicia n  deci des directl y f or t he C o njI ncisi o n Varia nt, a facilit y t hat 
all o ws i ncisi o n of t he c o nj u ncti va/te n o ns will be b o o ke d f or mas ki n g p ur p oses e ve n if t he 
s u bject will be fi nall y ra n d o mize d t o recei ve Oz ur de x ® . F or Oz ur de x®  t he C o njI ncisi o n 
Pr oce d ural Varia nt , i.e., s ur gical i ncisi o n of c o nj u n cti va/te n o n t he is n ot all o we d.  
P art A:  O pe n -la bel, parallel, ra n d o mize d, t w o treat me nt ar m part  of t h e st u d y wit h 
a p pr o xi matel y 1 8  a nti-V E G F treat me nt-naï ve or pre vi o usl y treate d s u bjects recei vi n g a si n gle 
treat me nt of mi d -d ose ( Ar m A 1) or hi g h -d ose ( Ar m A 2) O X U -0 0 1. S u bjects will be f oll o we d 
f or 5 2  wee ks  after treat me nt c o m pleti o n , wit h a safet y a nal ysis w he n t he l ast e nr olle d s u bject 
has c o m plete d Wee k 6  visit  a n d f urt her a n al ysis at Wee k 2 4 a n d Wee k 5 2.  
P art B:  Ra n d o mize d, mas ke d part i ncl u di n g a p pr o xi matel y  1 1 0 pre vi o usl y treate d  or  
treat me nt-naï ve s u bj ects . Treat me nt-naï ve s u bject s will c o m prise at least 5 5 s u bjects . T he 
f oc us of t he a nal ysis will be o n patie nt-rele va nt safet y e ve nts, i ncl u di n g e. g., t he occ urre nce 
rate of m o derate a n d se v ere oc ul ar A Es, A E SI, a n d oc ular S A Es re vi e we d b y D M C, a n d 
S p o ns or.  

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I n P art B t w o differe nt d ose le vels of O X U -0 0 1 will be a d mi nistere d . D ose 1 i n treat me nt ar m 
B 1 a n d D ose 2 i n treat me nt ar m B 2 will be c o m pare d t o I V T Oz ur de x 0. 7 m g  (treat me nt ar m 
B 3). D ose 1 is pla n ne d t o be O X U -0 0 1 1. 5 m g ( mi d -d ose) a n d D ose 2 O X U -0 0 1 3. 0 m g ( hi g h 
d ose). If p ote ntial safet y c o ncer ns arise fr o m t he wee k 6 a n al ysis i n Part A wit h t he hi g h d ose 
(treat me nt ar m A 2), t h e d ose i n Part B ma y be a dj uste d t o a d mi nister t he mi d-d ose of 
O X U -0 0 1  i n B 1 ( D ose 1, 1. 5 m g) a n d t he l o w d ose i n B 2 ( D ose 2 0. 7 5 m g). S u bjects will be 
f oll o we d f or 5 2 w ee ks  after treat me nt c o m pleti o n . I n Part  B, s u bjects a n d t he tea ms at t he 
i n vesti gati o nal site assessi n g  efficac y a n d s electe d q uesti o n naire assess me nts ( i.e., B C V A, 
S u bject’s  E x perie nce Ass ess me nt , a n d N EI -V F Q 2 5) a n d at t he C R C  rea d ers assessi n g t he 
C S T , are mas ke d t o t he s u bject’s treat me nt assi g n me nt. T he mas ke d site tea m will n ot ha ve 
a n y ot her st u d y r oles, w hic h c o ul d lea d t o i n v ol u ntar y u n mas ki n g.  
T he f oll o wi n g mas ki n g pr oce d ures will a p pl y i n Part B  (see Secti o n 7. 3 ): 
S u bjects will be mas ke d t o t heir assi g n me nt t o o ne of t he treat me nt ar ms ( B 1 -B 3). S u bjects 
will o nl y recei ve o ne st u d y treat me nt  o n Da y 0 ( Visit 2) , i.e., eit her s u prac h or oi dal 
a d mi nistrati o n of st u d y treat me nt ( O X U -0 0 1) or I V T Oz ur de x. N o s ha m treat me nt f or t he 
res pecti ve ot h er treat me nt will be a p plie d. I n a li mite d n u m ber of s u bjects i n t he O X U -0 0 1 
treat me nt ar ms, t he st u d y treat me nt will nee d t o be re peat e d i n a s ur gicall y e q ui p pe d 
pr oce d ure or o perati n g r o o m usi n g t he O X U -0 0 1 C o njI ncisi o n  P r oce d ural V aria nt. I n t his 
s u b gr o u p, a n i ncrease d ris k of getti n g hi nts t o t he assi g n me nt of a n O X U -0 0 1 treat me nt ar m 
e xist s. Still, e ve n i n t his setti n g n o i nf or mati o n a b o ut O X U-0 0 1 d ose gr o u p ca n be o btai n e d.  
I n a d diti o n, t he assess me nt tea ms at t he i n vesti gati o nal site perf or mi n g t he efficac y  a n d 
selecte d q uesti o n nair e assess me nts (i.e., B C V A, S u bject’s E x peri e nce  Assess me nt , a n d N EI-
V F Q 2 5) are m as ke d t o t h e s u bject’s treat me nt assi g n me nt , as well as t he gra ders at t he ce ntr al 
rea di n g c e nter ( C R C) ass essi n g t he C S T val ues . N o i nf or mati o n a b o ut t he nee d f or 
resc he d uli n g Part B s u bject f or t he O X U-0 0 1 C o njI ncisi o n  P r oce d ural V ari a nt will be s hare d.  
T his ma y re q uire s pecific rea ders or si milar o perati o nal meas ures f or t he C S T assess me nt, as 
ot her i ma gi n g li ke C F P , 4 Wi de-Fi el d I R Pl us i ma ges,  or peri p heral O C T ma y s h o w fi n di n gs 
(e. g., s u prac h or oi dal dr u g de p osits) gi vi n g hi nts o n t he treat me nt assi g n me nt.  St u d y 
treat me nts will be a d mi nistere d b y u n mas ke d  reti n al p h ysicia ns trai ne d o n t he O x ul u mis 
pr oce d ure, w h o will nee d t o k n o w t he treat me nt assi g n me nt of s u bjects.  
O n Visit 2 ( Da y 0), i n eit her Part  A or  B , s u bjects will recei ve st u d y treat me nt acc or di n g t o 
t heir ra n d o mize d assi g n me nt. T he sele cti o n of t he treat me nt setti n g a n d of t he res pecti ve 
varia nt of t he O X U -0 0 1 a d mi nistrati o n  pr oce d ure will f oll o w t he pre -treat me nt e x pert 

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assess me nt o n t he e x pect e d pr oce d ural c o m ple xit y. Alter nati ve s N o. 1-3 are s u m marize d i n 
Ta ble 3  a n d Ta ble 4  f or Part A a n d Part B. Treat me nts ca n be sc h e d ule d i n -cli nic ( N o. 1), 
directl y i n a s ur gic all y e q ui p pe d pr oce d ure r o o m or o perati n g r o o m ( N o. 2) or ca n i n case of 
n o n -c o m pleti o n i n a n i n -cli nic setti n g m o ve t o a s ur gicall y e q ui p pe d pr oce d ure r o o m or 
o perati n g r o o m ( N o. 3).  T he O X U -0 0 1 C o njI n cisi o n Pr oce d ural Varia nt s h o ul d o nl y be 
perf or me d i n a s ur gic all y e q ui p pe d pr oce d ure r o o m or a n o perati n g r o o m. De pe n di n g o n t he 
alter nati ve sce nari os  a n d ca use d b y e x p ecte dl y differe nt e q ui p me nt  of t h e tr eat me nt setti n gs, 
t he sc he d ule of acti vit y varies as s h o wn i n Ta ble 3  a n d Ta ble 4  f or Part A a n d Part B. 
I n a d diti o n t o t he scree ni n g a n d baseli ne visits, ( Visits 1 a n d 2, res pecti vel y), cli nic visits will 
occ ur o n Da y  1, a n d Wee k 1, 4, 6, 8,  a n d t he n e ver y f o ur  ( 4) wee ks t hereaft er f or a t otal d urati o n 
of fift y -t w o ( 5 2) wee ks after treat me nt c o m pleti o n . 
I n Part A, t he Wee k 6 visit  is sc he d ule d t o ca pt ure a n d assess a n y p ote ntial s afet y si g nals w hic h 
ma y start ar o u n d t his ti m e aft er ster oi d treat me nt ( e. g., I O P i ncrease). A safet y re vie w will occ ur 
after all acti ve st u d y partici pa nts ha ve c o m plete d Wee k 6 visit pri or t o i nitiati n g ra n d o mizati o n 
i n Part B. 
F or Part  B, t he Wee k 6 s afet y visit is o pti o nal a n d ma y be sc he d ul e d at t he discreti o n of t he 
i n vesti gat or base d, e. g., if s u bjects te n d t o prese nt wit h rele va nt I O P i ncrease t hr o u g h Wee k 4 
p ost -treat me nt. 
Starti n g at t he 
Wee k 1 2 visit, f or b ot h Parts A a n d B, s u bjects will be e val uate d b y t he 
i n vesti gat or ( mas ke d i n v esti gat or i n Part B) a gai nst pres pecifie d criteria i n dicati n g t he nee d f or 
f oll o w-o n treat me nt ( i.e., i n dicati n g t he e n d of t he c urre nt tr eat me nt i nter val). Criteria are as 
f oll o ws: 
1.  
At least 7 5 µ m t hic ke ni n g i n C S T o n S D -O C T c o m pare d t o best C S T val ue si nce t he 
baseli ne visit, Visit 2, Da y 0  
 or  
2.  
A decrease i n B C V A of ≥1 0 letters ( E T D R S) fr o m t he best ac hie ve d B C V A si nce t he 
baseli ne visit, Visit 2, Da y 0, t hat, i n t he o pi ni o n of t he i n vesti gat or, is d ue t o t he 
w orse ni n g of D M E.  
F or s u bjects s h o wi n g n o re d ucti o n of e de ma or n o i m pr o ve me nt of B C V A  after Visit 2, Da y 0 , 
t he baseli ne visit will be c o nsi dere d t he best C S T or B C V A val ue. 

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If acc or di n g t o t h e assess me nt of t he a b o ve criteri a, b y t he i n v esti gat or ( mas ke d i n vesti gat or i n 
Part B), t he n ee d f or a d mi nistrati o n of f oll o w -o n treat me nt is i n dicate d, s u bjects will be 
ma na ge d acc or di n g t o l ocal sta n dar d of care f or t he rest of t he tri al d urati o n. Sta n dar d of care 
treat me nts ma y i ncl u de I V T a nti-V E G F, oc ular I V T ster oi ds, or ot her n o n -i n vesti gati o nal 
treat me nts. 
I n Part B, w he n f oll o w -o n treat me nt criteria are m et base d o n mas ke d assess me nt, t he u n mas ke d  
i n vesti gat or will deter mi ne t he ki n d of f oll o w-o n treat me nt t o b e a d mi nistere d ( e. g., I V T a nti-
V E G F tr eat me nt, I V T st er oi d, or ot her) c o nsi d eri n g t he treat me nt hist or y a n d t he res p o nse t o 
t he st u d y treat me nt recei ve d. After recei vi n g t he first f oll o w -o n treat me nt i n t he st u d y e ye, 
s u bjects will c o nti n ue o n t he re g ular visit sc he d ul e t hr o u g h t he E n d-of -St u d y visit at Wee k 5 2.  
S u bjects w h o re q uire t hera p y f or c o m plicati o ns of dia betic e ye dise ase, e. g., ne wl y de vel o pe d 
P D R  a n d/ or ot her c o m plicati o ns will c o nti n ue t o be f oll o we d i n t his trial a n d will recei ve 
treat me nt f or D M E o n ce f oll o w-o n treat me nt criteria are met  (see Secti o n 7. 5. 2  f or details). 
S u bjects w h o deci de t o disc o nti n ue st u d y partici pati o n f or a n y reas o n  will u n der g o all e n d of 
st u d y visit assess me nts a n d pr oce d ures a n d t he visit will be c o nsi dere d a n e n d of st u d y visit.  If 
f or a n y reas o n t he st u d y treat me nt c a n n ot be a d mi nistere d, a n e xtr a e n d of st u d y visit is n ot 
necessar y  a n d o nl y acti vities f or Visit 2 nee d t o be c o m plete d  as a p plica ble . If a n y A Es/ A D Es 
w o ul d be o n g oi n g i n a s u bject i n w h o m treat me nt c o ul d e ve nt uall y  n ot be a d mi nistere d , 
u nsc he d ule d visits s h o ul d be perf or me d t o f ol l o w-u p s uc h e ve nts.  
If t he fell o w e ye re q uires ma na ge me nt f or D M E, t his s h o ul d be carrie d o ut acc or di n g t o t he 
l ocal sta n dar d of care b ut is n ot c o nsi dere d a st u d y treat me nt.  
I n Part A, treat me nt of t h e fell o w wit h oc ular ster oi ds s h o ul d be a v oi de d i n or der n ot t o 
c o nf o u n d P K assess me nts u ntil t he st u d y e ye has recei ve d f oll o w-o n t hera p y . After recei vi n g 
f oll o w-o n treat me nt i n t h e st u d y e ye, s u bjects will c o nti n ue o n t he re g ular visit sc he d ule 
t hr o u g h t he E n d-of -St u d y visit at Wee k 5 2.  
T his cli nical trial will i ncl u de a data m o nit ori n g c o m mittee ( D M C). T he D M C's mai n 
res p o nsi bilit y is t o peri o dicall y re vie w t he u n m as k e d  trial data a n d pr o vi de rec o m me n dati o ns 
re gar di n g t he tri al t o t he S p o ns or base d o n u n mas ke d be nefit/ris k assess me nt. Details o n t hese 
re vie ws i ncl u di n g ti mi n g a n d re vie w i nter vals will be lai d o ut i n a D M C C harter. 

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4. 1. 1  Scie ntific R ati o n ale f or t he St u d y Desi g n  
Di vi di n g t he st u d y i nt o t w o p arts:  
T he st u d y is di vi de d i nt o t w o parts t o c hec k f or p ote ntial safet y e ve nts o cc urri n g  i n t he first 
6  wee ks after a d mi nistrati o n of t w o d ose le vels of s u prac h or oi dal s ustai ne d -release O X U-0 0 1 
i n a t otal of 1 8 s u bjects. T he o pe n-la b el desi g n  of Part A will facilitate t he s afet y r e vie w . 
S u bjects will be ra n d o mize d t o o ne of t w o d os e le vels t o a v oi d bias wit h t he assi g n me nt of 
d oses b y t he i n vesti gat or . A re vie w of t he safet y data f or s u bjects i n Part A after t he last 
e nr olle d s u bject reac he d 6 wee ks . At t his ti mep oi nt, p ote ntial earl y safet y c o ncer ns  ( wit h t he 
a d mi nistrati o n pr oce d ure or wit h O X U -0 0 1) , w hic h  mi g ht i m pact t he c o n d uct of t he 
ra n d o mize d, mas k e d Part B are e x p ecte d t o ha v e ma nifeste d . 
C o ntr ol Ar m sele cti o n:  
Oz ur de x ®  w as select e d as a c o m parat or as it is t he c urre nt sta n d ar d of care f or mar ket e d  
i ntra vitreal ster oi ds f or D M E i n t he U S a n d E ur o p e. Als o , t he acti ve dr u g is De xa met has o n e, 
si milar t o t he De xa met has o ne  acet at e i n O X U-0 0 1  a v oi di n g a p ote ntial i m pact o n t he st u d y 
res ults b y differe nces i n ster oi d p ote nc y. A  ra n d o mizati o n of d ose le vels i n Part A a n d a 
ra n d o mizati o n t o o ne of t w o d ose le vels or a c o m p arat or ar m  i n Part B will all o w f or better 
i nter preta bilit y of t he trial res ults. It will als o facilitate i nter pretati o n of Oz ur de x®  res ults 
wit hi n t his trial a n d cr oss trial . Of n ote, t he treat me nt practice i n D M E has rele va ntl y c h a n ge d 
si nce t he first Oz ur de x®  trials, s o t hat patie nts are referre d earlier t o treat m e nt a n d wit h a 
tre n d t o less e xte nsi ve vis ual ac uit y l oss, w hic h is reflecte d i n t he eli gi bilit y criteria of t his 
trial. 
R a n d o miz ati o n r ati o:  
T he ra n d o mizati o n rati o is 2: 2: 1 wit h Ar m B 3, t he Oz ur de x ®  ar m ha vi n g o nl y 2 2 s u bjects ( vs. 
4 4 s u bjects i n O X U -0 0 1 Ar ms B 1 a n d B 2) t o bala nce t he ge n erati o n of hi g hl y usef ul 
c o m parati ve d ata w hilst mi ni miz i n g a n y e x p os ure t o si de effects of t he c o m parat or 
( Oz ur de x® ). Of n ote, t he i m pact of Oz ur de x®  o n l e ns o paciti es t y picall y ma nifests i n t he 2n d 
year of c o nti n ue d treat me nt  (i.e., i m pla nts a d mi nistere d at i nter v als of 6 m o nt hs  or s h orter)  
wit h t he pea k i n cat aract s ur geries i n t he M E A D trial bet wee n 1 8 a n d 3 0 m o nt hs. A si n gle 
Oz ur de x ® a d mi nistrati o n i n t he c urre nt trial is e x p ecte d t o ha v e a c o m para bl y li mite d i m pact 
o n le ns o pacities.  If s u bjects w o ul d ha ve bee n  ra n d o mize d a n d c o ul d n ot be treate d, t hes e 
s u bjects will be re place d u ntil t he tar gete d n u m ber  of s u bjects  per trial p art are reac he d.  

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Str atific ati o n f or pri or a nti -V E G F tre at me nt:  
S u bjects are stratifie d i nt o t h ose pre vi o usl y treate d wit h a nti -V E G F t hera p y a n d t h ose w h o are 
a nti-V E G F naï ve as t he treat me nt hist or y wit h a nti -V E G F is k n o w n t o i m pact res p o nse t o 
ster oi ds b ot h a nat o micall y a n d f u ncti o nall y. I n Part A, n o mi ni m u m n u m ber of treat me nt -
naï ve s u bjects is defi ne d. T heref ore , n o stratificati o n will be a p plie d i n Part A.  
Vari a nts of t he O x ul u mis ®  pr oce d ure  
I n t his trial, t he a d mi nistrati o n of O X U-0 0 1 wit h t he O x ul u mis ill u mi nate d micr ocat heter will 
be perf or me d wit h t w o differe nt pr oce d ural varia nts de pe n di n g o n s u bject c haract eristics a n d 
pr oce d ural s uccess:  
1.  Sta n dar d Vari a nt : A d mi nistrati o n wit h t he O x ul u mis® de vice wit h o ut a n i ncisi o n 
of t he c o nj u ncti va/te n o ns. T he sta n dar d varia nt ca n be perf or me d i n a n y setti n g, 
i.e., i n-cli nic, i n a pr oce d ure r o o m or i n a n o perati n g r o o m.  
2.  C o njI ncisi o n Varia nt:  I ncisi o n of t he c o nj u ncti va/te n o ns at t he start of t he O X U-
0 0 1 a d mi nistrati o n t o i ncrease visi bilit y a n d access f or t he scleral e n ga g e m e nt 
p hase of t he O X U -0 0 1 a d mi nistrati o n. T he i ncisi o n o pe ni n g of t he 
c o nj u ncti va/te n o ns nee ds t o be cl ose d b y usi n g sta n dar d s ur gical tec h ni q ues a n d 
material ( e. g., fi bri n gl ue, s ut uri n g material): T his varia nt ca n b e use d at t he 
discreti o n of t he treati n g p h ysicia n eit her a) i nitiall y if s u bject c haracteristi cs 
a n d/ or me dical hist or y s u g gest t his varia nt, or b) if wit h t he  Sta n dar d O X U -0 0 1 
a d mi nistrati o n varia nt, st u d y treat me nt ca n n ot b e a d mi nistere d.  
All o wi n g t hese varia nts will all o w f or a ver y hi g h c o m pleti o n rate of t he pr oce d ure.  
Pri m ar y e n d p oi nt selecti o n:  
As t his is t he first st u d y assessi n g O X U -0 0 1 i n h u ma n s u bjects, safet y is t h e pri mar y 
e n d p oi nt. 
F oll o w -o n tre at me nt criteri a:  
C S T t hic ke ni n g a n d B C V A l oss are t he t w o mai n tri g gers f or treat me nt i n p atie nts wit h D M E  
i n a cli nical setti n g. Acc or di n gl y, criteria f or w orse ni n g of e de ma a n d  visi o n l oss  were 

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selecte d as pre-s p ecifie d criteria f or t he nee d f or f oll o w-o n treat me nt i n t his st u d y base d o n 
nat ural disease fl uct uati o n a n d e x peri e nce fr o m ot her st u dies assessi n g si milar p o p ulati o ns.  
D ur ati o n of t he st u d y:  
T he d urati o n of t he st u d y ( 5 2 wee ks  fr o m treat me nt c o m pleti o n) is base d o n t he e x pect e d 
d urati o n of t he efficac y of O X U -0 0 1. We e x pect t hat t he maj orit y of s u bjects will ha ve met 
t he f oll o w-o n treat me nt criteria b y wee k 5 2 i n t he O X U -0 0 1 treat me nt ar ms of t his cli nical 
trial. 
4. 2  
J ustific ati o n of D ose  
To deter mi ne t he d oses f or t he first -i n-h u ma n cli nical trial, o utc o mes fr o m pri mar y 
p har mac o ki netic st u dies of t he effects of D M A micr os p here f or m ulati o ns a d mi nistere d via t he 
s u prac h or oi dal s p ace i n r a b bit m o dels of h V E G F-i n d uce d reti nal v asc ular l ea ka g e ha ve b ee n 
e val uate d (v ol u me  of a ra b bit e ye is a p pr o xi matel y 4 0 % of t he  h u ma n e y e v ol u me ). I n ra b bits, 
u p t o 5 m g i n 4 0 µ L of D M A micr os p here f or m ulati o n has bee n well -t olerat e d i n t hese m o dels 
w he n a d mi nistere d as a si n gle s u prac h or oi dal i njecti o n t o b ot h e yes wit h p ost -treat me nt 
f oll o w-u p f or 1 0 5 da ys. I n a n ot her st u d y, s u prac h or oi dall y a d mi nistere d micr os p here 
f or m ulati o ns c o ntai ni n g a p pr o xi matel y 0. 9 t o 1. 3 m g of D M A were c o m pare d t o a s ha m 
s u prac h or oi dal pr oce d ure or t he p ositi ve c o ntr ol O z ur de x i m pla nt (all o metri c d ose of 0. 3 5 m g 
de xa met has o ne) i njecte d i nt o t he vitre o us. D M A micr os p here f or m ulati o ns de m o nstrate d a 
d ose -de pe n d e nt s u p pressi o n of i n d uce d fl u ores cei n l ea k b ut less pea k s u p pressi o n t ha n 
Oz ur de x ®  u p t o t he first 3 0 da ys after a d mi nistrati o n. T hereafter, t he Oz ur de x effect r a pi dl y 
dissi pate d beca use of  dr u g de pleti o n w hile e de ma s u p pressi ve effects of t he micr os p here 
f or m ulati o ns were m ai ntai ne d u p t o t he e n d of t he st u d y at da y 6 0. T he s electi o n of t he d ose 
le vels f or t he cli nic al trial, t heref ore, has bee n bas e d o n ac hie vi n g mea ni n gf ul effect w hile 
als o c o nsi deri n g c u m ulati ve effects of l o n ger e x p os ure d urati o n as c o m pare d t o Oz ur de x ® . As 
t he micr os p here s us p e nsi o ns are e x p ecte d t o c o nti n ue sl o w-release of D M A o ver a peri o d i n 
e xcess of 6 m o nt hs, l o n g er-ter m p h ar mac o ki netic st u dies i n ra b bits wit h D M A micr os p here 
f or m ulati o ns c o ntai ni n g u p t o a p pr o xi matel y 1. 5 m g D M A s h o w t he micr os p heres t o be well 
t olerate d u p t o st u d y e n d at 2 2 0 da ys p ost-a d mi nistrati o n. Acc or di n gl y, a 3. 0 m g D M A 
micr os p here d os e (e xtr a p olate d fr o m t he all o metri c 1. 5 m g D M A d ose i n ra b bits) is 
c o nsi dere d t he t ar get t hera pe utic d ose  f or h u ma n use. D oses of 1. 5 m g a n d 3. 0 m g  will be 
e val uated i n parallel  i n Part A as c u m ulati ve effects of sl o w-release D M A ma y be e q uall y 
effecti ve as 3. 0 m g w hile re d uci n g  t he d ose e x p os ure . T he Wee k 6 safet y assess me nt i n Part A 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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Pa ge 6 8  of  1 6 9  
of t he O X U C T-1 0 2 trial is c o nsi dere d a n a p pr o priate ti me p oi nt t o l o o k f or i n dicati o ns of d ose -
de pe n de nt a d v erse effect s, e. g., I O P i ncreases. Base d o n t his s yste mic data re vie w wit h t he 
partici pati o n of a n i n de p e n d e nt D M C, d oses f or t he ra n d o mize d Part B of t he trial will be 
c o nfir me d. If t here is a n earl y i n dicati o n f or d ose -de pe n de nt saf ety c o n cer ns wit h t he 3. 0 m g 
d ose, b ut n ot wit h t he 1. 5 m g d ose, t he sec o n d d ose i n Part B w ill be c h ose n t o c o ntai n 
0. 7 5  m g D M A micr os p heres.  
4. 3  
E n d -of -St u d y Defi niti o n  
T he e n d of t he st u d y is d efi ne d as t he d ate of t he l ast visit of t he last s u bject i n t he st u d y.  
A s u bject is c o nsi dere d t o ha ve c o m plete d t h e st u d y if t he s u bject has c o m plete d all peri o ds of 
t he st u d y i ncl u di n g t he last visit. 
5  
St u d y P o p ul ati o n  
5. 1  
I ncl usi o n Criteri a 
S u bjects are eli gi ble t o b e i ncl u de d i n t he st u d y o nl y if A L L t he f oll o wi n g criteria a p pl y:  
1.  
A ble t o u n dersta n d a n d si g n a n i nf or me d c o ns e nt f or m.  
2.  
At least ei g htee n ( 1 8) years of a g e at t he ti me of s cree ni n g.  
3.  
Ha ve bee n dia g n ose d wit h T y pe 1 or T y pe 2 dia betes mellit us.  
4.  
Ha ve D M E i n v ol vi n g t he ce nter of t he f o vea wit h ce ntral s u bfiel d t hic k n ess ( C S T) i n t he 
st u d y e ye at t he scree ni n g visit, c o nfir me d b y t he C R C, of at least 3 2 0 µ m o n S D O C T 
( meas ure m e nt fr o m t he R P E t o I L M, i ncl usi vel y). 
5.  
Ha ve B C V A i n t he st u d y e ye bet w ee n 3 4 a n d 7 8 l etters E T D R S (a p pr o xi m ate S nelle n 
ac uit y of 2 0/ 2 0 0 – 2 0/ 3 2) at t he scree ni n g visit. F or eli gi bilit y assess me nts, o nl y t he 
E T D R S B C V A letter  sc ore is c o nsi dere d rele va nt. 
6.  
F or w o me n w h o are n ot p ost me n o pa usal ( i.e., at l east  1 2 m o nt hs of n o n -t hera p y-i n d u ce d 
a me n orr hea or s ur gicall y sterile (a bse n ce of o vari es a n d/ or uter us) a gree m e nt t o re mai n 
a bsti ne nt or use c o m bi ne d c o ntrace pti ve met h o ds t hat res ult i n a fail ure rat e of less t ha n 
1 % per year fr o m t he treat me nt visit (Visit 2, Da y 0) u ntil t he e n d of trial partici pati o n, 
or , if s u bjects disc o nti n ue trial partici pati o n bef ore Wee k 5 2, f or at least 5 2  wee ks fr o m 
t he treat me nt visit ( Visit 2, D a y 0). l. E xa m ples of c o ntrace pti ve met h o ds wit h a n 
e x pecte d fail ure rate of l ess t ha n 1 % per year i ncl u de male sterilizati o n, h or m o nal 
i m pla nts, pr o per use of c o m bi ne d oral or i njecte d h or m o nal c o ntrace pti ves, a n d cert ai n 

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C O N FI D E N TI A L  
Pa ge 6 9  of  1 6 9  
i ntra uteri ne de vic es. Alter nati vel y, t w o met h o ds (e. g., t w o barrier met h o ds s uc h as a 
c o n d o m a n d a cer vical ca p) ma y be c o m bi ne d t o ac hie ve a fail ure rate of l ess t ha n 1 % 
per year . Barri er met h o ds m ust al wa ys be s u p ple me nte d wit h t he use of a s per mici de.  
7.  
Males m ust a gree t o use a barri er met h o d of c o ntr ace pti o n starti n g fr o m t h e treat me nt 
visit ( Visit 2, Da y 0) u ntil t he e n d of trial partici pati o n, or , if s u bjects disc o nti n ue trial 
partici pati o n bef ore Wee k  5 2,  f or at least 5 2  wee ks fr o m t he treat me nt visit ( Visit 2, 
D a y 0).  
8.  
S u bject m ust be willi n g n ot t o partici pate i n a n y ot her cli nical trial i ncl u di n g a n 
i n vesti gati o nal me dici nal pr o d uct (I M P) or a n i n vesti gati o nal de vice u ntil t he e n d of trial 
partici pati o n . 
N ote o n i ncl usi o n criteri o n N o. 4: Practicall y,  t he i nitial eli gi bilit y deter mi nati o n at t he site will 
use t he 3 2 0 µ m t hres h ol d f or C S T f or all partici p a nt s a n d f or all S D-O C T d e vices all o we d i n 
t his trial (see Secti o n 9. 3. 6 ). T he C R C will t he n als o assess t he C S T a n d c o nfir m eli gi bilit y. 
5. 2  
 E xcl usi o n Criteri a  
S u bjects are eli gi ble t o b e i ncl u de d i n t he st u d y o nl y if N O N E of t he f oll o wi n g criteria a p pl y:  
1.  
Prese nce of a n y si g nifica nt oc ular or n o n -o c ular disease/ dis or der ( or me dicati o n 
a n d/ or la b orat or y t est a b n or malities) w hic h, i n t he o pi ni o n of t he I n vesti gat or a n d wit h 
t he c o nc urre nce of t he O x ular Me dical M o nit or, ma y  
1.  
p ut t he s u bject at ris k beca use of partici pati o n i n t he trial , or 
2.  
i nfl ue nce t he res ults of t he trial, or 
3.  
i nfl ue nce t he s u bject’s a bilit y t o partici pate i n t he trial, or  
4.  
ma y re q uire m e dical or s ur gical i nter ve nti o n d uri n g st u d y partici pati o n ( e. g., 
cataract, vitre o us he m orr ha ge, reti nal d etac h me nt, or mac ular h ol e) . 
2.  
Mac ular e de ma c o nsi dere d d ue t o a ca use ot her t ha n dia betes mellit us i n eit her e ye.  
3.  
C o n diti o n, i n t he st u d y e ye, i n w hic h vis ual ac uit y is n ot e x pecte d t o i m pr o ve fr o m t he 
res ol uti o n of mac ul ar e de ma (e. g., f o veal atr o p h y, cli nicall y rele va nt l oss of t he elli ps oi d 
z o ne, pi g me nt a b n or malities, vitre o mac ular tracti o n, or n o nreti nal ca uses)  as 
deter mi ne d b y t he i n vesti gat or wit h t he c o n c urre nce of t h e O x ular Me di cal M o nit or 
s u p p orte d b y a re vie w b y t he C R C. 
4.  
C o n diti o ns, i n t he st u d y e ye, t hat ma y re n der t h e a d mi nistrati o n of st u d y treat me nt 
i ntra vitreal i m pla nt i nserti o n or s u prac h or oi d al micr ocat h eter i nserti o n a n d 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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Pa ge 7 0  of  1 6 9  
de pl o y me nt diffic ult or s u bject t he patie nt t o e xcessi ve ris k of c o m plicati o ns. 
E xa m ples i ncl u de b ut are n ot li mite d t o  oc ular s urface dise ase wit h si g nifica nt 
c o nj u ncti val e de ma a n d/ or i nfla m mati o n,  oc ular h y p ot o n y, scleral sta p h yl o mas, 
necr otizi n g scleritis, scleral melti n g, e xcessi ve c h or oi dal scarri n g e. g., ass o ciate d wit h 
pa n -reti nal p h ot oc o a g ulati o n, a m o n gst ot hers. 
5.  
Mac ular laser p h ot oc oa g ulati o n or pa nreti nal laser p h ot oc oa g ulati o n ( P R P) i n t he st u d y 
e ye perf or me d wit hi n si xtee n ( 1 6) wee ks pri or t o scree ni n g.  
6.  
Acti ve pr oliferati ve  dia b etic reti n o pat h y ( P D R) or se q uelae of P D R (i ncl u di n g iris 
ne o vasc ularizati o n, vitre o us he m orr ha g e, tracti o nal reti nal detac h me nt, e xte nsi ve 
scarri n g f oll o wi n g P R P) at scree ni n g i n t he st u d y e ye. 
7.  
Hist or y of rec urre nt or acti ve i ntra oc ular i nfla m mati o n i n eit her e ye ( e. g., u v eitis) wit hi n 
1 2  wee ks pri or t o scree ni n g.  
8.  
I nfecti o us e y e disease li ke i nfecti o us ble p haritis, keratitis, or c o nj u ncti vitis i n eit her e ye 
wit hi n f o ur ( 4) wee ks of scree ni n g.  
9.  
I O P ≥ 2 2 m m H g, or gla uc o mat o us disc c ha n ges (i.e., a c u p disc rati o great er t ha n 0. 8) 
i n t he st u d y e ye at scree ni n g . Hist or y of gla uc o ma s ur ger y, a n d/or c urre nt a nti -gla uc o ma 
t hera p y wit h m ore t ha n t w o acti ve s u bsta n ces (i n s e parat e or a c o m bi nati o n pre parati o n) 
are e x cl usi o nar y.  
1 0.  
Hist or y of cl ose d -a n gle gla uc o ma.  
1 1.  
I O P < 6 m m H g ( h y p ot o n y) i n t he st u d y e ye  at scree ni n g . 
1 2.  
S p herical e q ui val e nt of t he refracti ve err or of −6 di o pters of m y o pia or w orse ( pri or t o 
cataract or refracti ve s ur ger y) at scree ni n g.  
1 3.  
Cataract or ot her m e dia o pacit y t hat li mits t he a bilit y t o o btai n t he pla n ne d i ma gi n g 
assess me nts.  
1 4.  
Hist or y of reti nal detac h me nt.  
1 5.  
Pri or treat me nt wit h I V T a nti -V E G F i n t he st u d y e ye 
1.  
Treat me nt -n aï ve gr o u p ( Part A a n d B ):  
A n y I V T a nti -V E G F treat me nts i n t he st u d y e ye are e xcl usi o nar y re g ar dless of 
t he ti me i nter val si nce i njecti o n. 
2.  
Pre vi o usl y treate d gr o u p  ( Part A a n d B): 
S u bjects i n t he pre vi o usl y treate d gr o u p are e x cl u de d if t he y meet a n y of t he bel o w 
criteria f or t he st u d y e ye at scree ni n g : 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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C O N FI D E N TI A L  
Pa ge 7 1  of  1 6 9  
a)  S u bject has recei v e d less t ha n t hree ( 3) a nti -V E G F i njecti o ns si nce treat me nt 
i nitiati o n. (at least t hree i njecti o ns m ust ha ve bee n recei v e d f or eli gi bilit y) 
b)  Ti me i nter val b et wee n t he first a nti -V E G F i njecti o n a n d scree ni n g is m ore 
t ha n si xt y-f o ur ( >6 4 ) wee ks. 
c)  Last i njecti o n wit h ra ni biz u ma b or be vaci z u ma b wit hi n f o ur ( 4) wee ks pri or 
t o scree ni n g. 
d)  Last i njecti o n wit h afli berce pt wit hi n ei g ht ( 8) wee ks pri or t o scree ni n g.  
e)  Last i njecti o n wit h farici ma b or br ol uciz u ma b wit hi n t wel ve ( 1 2) wee ks 
pri or t o scree ni n g.  
f) Pri or treat me nt 
wit h S U S VI M O ( P ort 
Deli v er y S yste m) i m pla nt is 
e xcl usi o nar y.  
1 6.  
Pri or oc ular treat me nt wit h ster oi d i njecti o ns ( peri oc ular, s u bte n o n, i ntra vitreal) or 
i ntra vitreal i m pla nts i n t he st u d y e ye. A hist or y of t o pical oc ular ster oi ds is n ot 
e xcl usi o nar y.  
1 7.  
Part A  o nl y: Pri or oc ular treat me nt wit h ster oi d i njecti o ns ( peri oc ul ar, s u bte n o n, 
i ntra vitreal) or i ntra vitreal i m pla nts i n t he fell o w e ye ( d ue t o p ote ntial i nterfere nce 
wit h P K meas ure me nts).  
1.  
Last i njecti o n (i ntra - or peri oc ular /s u bte n o n) wit h tria mci n ol o ne acet o ni de 
wit hi n t wel ve  (1 2 ) wee ks  bef ore s cree ni n g.  
2.  
Last i njecti o n ( s u prac h or oi dal) ster oi ds, e. g., Xi pere ™, wit hi n t wel ve ( 1 2) 
wee ks bef ore s cree ni n g.  
3.  
Last i njecti o n (I V T) wit h de xa met has o ne i m pla nt ( Oz ur de x ® ) wit hi n 
t we nt y-f o ur (2 4 ) wee ks  b ef ore s cree ni n g.  
4.  
Pri or treat me nt wit h l o n ger d urati o n i m pla nts ( e. g., fl u oci n ol o ne acet o ni de I V T 
i m pla nt, Il u vie n) is e x cl usi o nar y. 
1 8.  
Pri or treat me nt wit h s u pr ac h or oi dal ster oi ds  i n t he st u d y e ye is e xcl usi o nar y. 
1 9.  
C o nc urre nt use of s yste mic gl uc oc ortic oi d me dicati o ns or s yste mic ster oi ds wit hi n 
t wel ve ( 1 2) wee ks b ef ore scree ni n g is e x cl usi o nar y. I ntr a nasal, i n hal e d, a n d e xtra-
oc ular t o pical c ortic oster oi ds are all o we d .  

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C O N FI D E N TI A L  
Pa ge 7 2  of  1 6 9  
2 0.  
Pri or I V T or s u pr ac h or oi dal treat me nt wit h i n vesti gati o nal a ge nts i n eit her e ye ( e. g., 
a ge nts wit h a nti -V E G F acti vit y, or c o m bi ne d p h ar mac ol o gic acti vit y, ge ne t hera pies, 
cell t hera pies, or a n y ot h er t hera pe utic m o dalit y ) at a n y ti me. 
2 1.  
Partici pati o n i n a cli nic al trial i n w hic h a n i n vesti gati o nal dr u g ( wit h ot her r o utes of 
a d mi nistrati o n t ha n I V T or s u prac h or oi d al) was a d mi nistere d wit hi n 9 0 da ys of 
scree ni n g or 5 half-li ves of t he i n vesti gati o nal dr u g, w hic he ver is l o n ger. 
2 2.  
Treat me nt wit h ocri plas mi n (Jetrea ® ) at a n y ti me. 
2 3.  
Hist or y of vitre oreti nal s ur ger y (i ncl u di n g s ur ger y f or reti nal detac h m e nt or scleral 
b uc kle) i n t he st u d y e ye. Vitrect o m y is o nl y e xcl usi o nar y, if wit hi n t wel ve ( 1 2) wee ks 
pri or t o scree ni n g.  
2 4.  
A n y ot her pre vi o us o p ht hal mic s ur geries, 
u nc o m plicate d cataract s ur ger y, or 
u nc o m plicate d tra u ma i n t he st u d y e ye wit hi n t wel ve ( 1 2) wee ks pri or t o scree ni n g. 
C o m plicate d cataract s ur ger y or tra u ma t hat ma y i m pact access a n d/ or dr u g deli ver y t o 
t he s u prac h or oi dal s pace are e x cl usi o nar y. 
2 5.  
Part B o nl y: A n y hist or y of s ur gical c o m plicati o ns i n t he st u d y e ye t hat ma y i ncreas e 
t he ris k of a nteri or c ha m ber mi grati o n of i ntra vitreal i m pla nts (e. g., t or n or r u pt ure d 
p osteri or le ns ca ps ule, i m pla ntati o n of a n y iris -fi xate d or s clera-fi xate d i ntra oc ular 
le nses, iri dect o m y) re gar dless of t he ti me i nter val bet wee n t he pr oce d ure a n d t he st u d y 
e nr oll me nt.  
2 6.  
H y perse nsiti vit y t o O X U -0 0 1, or a n y of t h e e xci pi e nts i n t he O X U -0 0 1 f or m ulati o n or 
O x ul u mis ®  de vice c o m p o ne nts.  
2 7.  
Part B o nl y : H y perse nsiti vit y t o c o m p o ne nts of Oz ur de x ®  f or. 
2 8.  
Acti ve mali g na nc y or hist or y of mali g na nc y wit hi n t he past fi ve ( 5) years.  
2 9.  
U nc o ntr olle d dia b etes 
wit h a he m o gl o bi n 
A 1c ( H b A 1c) > 1 2 % or a n y ot her 
u nc o ntr olle d s yste mic disease at s cree ni n g.  
3 0.  
U nc o ntr olle d h y perte nsi o n, defi ne d as bl o o d 
press ure 
wit h a s yst olic val ue of 
≥ 1 6 0 m m H g or a diast olic val ue of ≥ 1 0 0 m m H g u p o n re peat assess me nt at scree ni n g.  
3 1.  
Hist or y of m y ocar dial i nfarcti o n, str o k e, tra nsie nt isc he mic attac k, ac ut e c o n gesti ve 
heart fail ure, or a n y ac ut e c or o nar y e v e nt wit hi n 9 0 da ys bef ore scree ni n g.  
3 2.  
S u bjects w h o are pre g na nt or breastf ee di n g at t he scree ni n g visit, or w h o test p ositi ve 
f or pre g n a nc y at t he s cree ni n g visit or are u n willi n g t o use a de q uate birt h c o ntr ol 
met h o ds t o pre ve nt pre g n a nc y t hr o u g h o ut t he st u d y.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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3 3.  
S u bjects w h o were pre vi o usl y ra n d o mize d i n t his trial, b ut i n w h o m a d mi nistrati o n of 
st u d y treat me nt c o ul d n ot be c o m plete d. 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 7 7  of  1 6 9  
6. 1  
O X U -0 0 1 –  D E X A s p heres A d mi nistere d wit h t he O x ul u mis ®  
O X U -0 0 1 is a n o p ht hal mic s ustai ne d-rel ease d e xa met has o ne acetate micr os p here f or m ulati o n 
( D E X As p heres® ), w hic h is i nte n de d f or s u prac h or oi dal a d mi nistrati o n usi n g t he O x ul u mis®  
O p ht hal mic A d mi nistrati o n De vice.  
O X U -0 0 1 is classifie d as a me dici nal pr o d uct re g ulate d  i n t he U S u n der 2 1 C F R 4 as a 
c o m bi nati o n pr o d uct  as d efi ne d i n 2 1 C F R 3. 2 (e) .  I n t he E U, O X U -0 0 1 is re g ulate d u n der 
Directi ve 2 0 0 1/ 8 3/ E C  as a c o m bi nati o n pr o d uct,  w hic h i ncl u des t he dr u g a n d t he 
a d mi nistrati o n de vice.  
To f ulfill t he G S P R re q uire me nts of t he E U M D R A n ne x I  f or t he me dical de vice c o m p o n e nt, 
t he o bjecti ves f or e val uati n g t he de vice safet y a n d perf or ma n ce are s e paratel y o utli ne d i n t he 
latest versi o n of t he O x ul u mis® Cli nical E val uati o n Pla n ( C E P) Versi o n O X U C T -1 0 2.   
6. 1. 1  De x a met h as o ne Acet ate Micr os p heres ( D E X As p here s® ) 
T he O X U -0 0 1 dr u g pr o d uct is a s us pe nsi o n of p ol y mer/ dr u g micr os p heres c o ntai ni n g 
de xa met has o ne acetate ( D M A) i n a n e x ci pie nt f or m ulati o n, w hic h is s u p plie d as a sterile, 
l y o p hilize d pr o d uct re q uiri n g rec o nstit uti o n j ust pri or t o a d mi nistrati o n. 
 
 
S u bjects e nr olle d i n t he cli nical trial will recei ve a sta n dar d v ol u metric d os e of O X U -0 0 1 of 
6 0 µl f or t he 3. 0 m g, a n d t he 1. 5 m g d ose, or 3 0 µl f or t he 0. 7 5 m g  d ose. T he  dr u g c o nte nt f or 
t he res pecti ve d ose le vels will be varie d t hr o u g h t h e micr os p here c o nce ntrati o n fr o m t he 
l y o p hilize d f or m ulati o n t o ac hie ve t h e 3. 0 m g, 1. 5 m g, or 0. 7 5 m g  O X U -0 0 1 st u d y treat me nt 
(f or a d etaile d des cri pti o n of rec o nstit uti o n a n d dr u g ha n dli n g see f urt her i nf or mati o n i n t he 
O X U C T -1 0 2 p har mac y ma n ual) . T he s ustai n e d-release O X U -0 0 1 dr u g pr o d uct is c urre ntl y 
n ot a p pr o ve d i n a n y c o u ntr y a n d t heref ore, is a n i n vesti gati o nal dr u g/ me dici nal pr o d uct.  
6. 1. 2  O x ul u mis ®  S u pr ac h or oi d al O p ht h al mic A d mi nistr ati o n De vice  
T he O x ul u mis ® O p ht hal mic A d mi nistrati o n De vice will be use d t o a d mi nister O X U -0 0 1 t o 
t he s u prac h or oi dal s pace via ill u mi nate d micr ocat heterizati o n . 
I n t otal f or t he o p ht hal mic a d mi nistrati o n pr oce d ure t o t he s u prac h or oi dal s pace, t he f oll o wi n g 
t hree me dical de vices will be use d i n t his cli nical trial. 
1.  
O x ul u mis ®  i n vesti gati o nal o p ht hal mic a d mi nistrati o n de vice ( n o n-C E mar ke d)  

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2.  
Merit Me dical L uer s yri n ge, 2 5 0 µl ( C E -mar ke d)  
3.  
N o va E ye Me di cal i L u mi n ™ Fi ber o ptic Ill u mi nat or ( C E -mar k e d)  
6. 1. 2. 1  Devic e M a n uf act uri n g Pr ocess  
 
 
 
  
T he C M O a n d all s u bc o ntract ors are I S O  1 3 4 8 5 certifie d.  T here are n o s pecial pr ocesses us e d 
i n t he ma n ufact ur e of t he O x ul u mis®  de vice. All pr ocesses h a ve a hist or y of use i n t he 
ma n ufact ur e of me dic al de vices.  
T he de vice c o m p o ne nts are recei ve d, q uara nti ne d, a n d i ns pecte d t o meet t heir res pecti ve 
s pecificati o ns. Rele ase d c o m p o ne nts are assi g ne d q ualit y c o ntr ol i de ntificati o ns a n d place d 
i nt o i n ve nt or y f or pr o d ucti o n. Refer t o t he O x ul u mis ®  I nstr ucti o ns f or Use (Versi o n: 
O X U C T -1 0 2 ) f or de vice asse m bl y a n d O X U-0 0 1 a d mi nistrati o n pr oce d ures.  
6. 1. 2. 2  I nte n de d Perf or m a nce a n d C o ntr ai n dic ati o ns 
T he O x ul u mis ®  de vice is i nte n de d f or t he a d mi nistrati o n of t hera p e utic m o dalities, e. g., dr u gs 
t o t he s u prac h or oi dal s p ace of a n e ye f or t he treat me nt of diseases a n d c o n diti o ns of t he 
p osteri or se g me nt a n d u v eal tract of t he e ye.  
T he  de vice  is i nte n d e d f or use o nl y b y certifie d me dical practiti o ners trai ne d i n reti nal disease 
ma na ge me nt. T h ese s pecialize d p h ysicia ns s h o ul d be a de pt i n i ntra oc ul ar dr u g a d mi nistrati o n 
a n d i n t he use of ma n u al o p ht hal mic i nstr u me nts. T he use setti n g i s si milar t o t he setti n g f or 
I V T i njecti o ns, w hic h ma y var y bet wee n ge o gra p hies a n d i ncl u des pr oce d ure, o perati n g 
r o o ms, or reti nal p h ysicia n’s cli nics. O nl y i n s u bjects w here t h e pr oce d ural C o njI ncisi o n  
V aria nt is perf or me d , a tr eat me nt setti n g i n a s ur gicall y e q ui p pe d pr oce d ure / o perati n g r o o m  is 
nee de d. T h e o pe ni n g a n d cl os ure of t he c o nj u ncti va/te n o ns t o s u p p ort t he O x ul u mis pr oce d ure 
is a s mall, r o uti ne pr oce d ure a n d will be perf or m e d i n li ne wit h l ocal s ur gical practice. 
C o ntrai n dicati o ns f or t he a d mi nistrati o n of treat me nts wit h t he O x ul u mis ®  de vice  are 
reflecte d i n t he e xcl usi o n criteria of t his trial (s ee Secti o n  5 . 2, e. g., e xcl usi o n criteri a 4  -1 2)  
a n d i ncl u de b ut are n ot li mite d t o oc ular s urface diseases wit h si g nifica nt c o nj u ncti val e de ma 
a n d/ or i nfla m mati o n, acti ve oc ular or peri oc ul ar i nfecti o ns, scleral ectasi a, oc ular h y p ot o n y, or 
str uct ural a b n or m alities li ke c h or oi dal c ol o b o ma, a n d c h ori oreti nal a nast o m osis.  

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T he materials use d i n t he O x ul u mis ®  were select e d f or a p pr o priate mec ha nical pr o perties, 
o ptical pr o perties, a n d bi oc o m pati bilit y of t he tiss ue a n d fl ui d c o ntact c o m p o ne nts.  T he tiss ue 
a n d dr u g fl ui d pat h wa y c o ntacti n g p orti o ns of t he O x ul u mis ®  ha ve bee n teste d t o I S O 1 0 9 9 3 
f or bi oc o m pati bilit y ass ura nce, h o we ver, s u bject-s pecific se nsiti vit y ma y occ ur t o t he 
f oll o wi n g tiss ue a n d dr u g fl ui d pat h wa y c o ntacti n g c o m p o ne nts of t he de vice: 
 
 
  
6. 1. 2. 3  Devic e Descri pti o n  
T he O x ul u mis ®  (Fi g ure 3 ) is a sterile, ma n uall y o p erate d, mi ni mall y i n vasi ve, si n gle-use 
de vice desi g ne d t o d e pl o y a t hera p e utic dr u g deli v er y -g ui di n g ill u mi nate d o p ht hal mic 
micr ocat heter i nt o t he s u prac h or oi d al s pace t o a d mi nister t hera pe utic m o d alities, i ncl u di n g 
dr u gs. T he il l u mi nati o n c o nfir ms t hat t he micr ocat heter is de pl o ye d c orrectl y, pri or t o 
a d mi nistrati o n of t he t hera pe utic me dici nal pr o d u ct. T he de vice c o nsists of a 2 7 -ga u ge  n ee dle 
c o ntai ni n g a micr ocat het er. T he nee dle is i nserte d i nt o t he sclera i n t he re gi o n of t he pars 
pla na, at a n ac ute a n gl e t o t he sclera, w hile ai mi n g p osteri orl y. T he tri g ger is acti vate d after 
t he nee dle ti p has f ull y e ntere d t he scl era; t he n ee dle is t he n a d va nce d f urt her u ntil t he 
micr ocat heter a ut o maticall y de pl o ys i nt o t he s u prac h or oi dal s pace. After t h e micr ocat h eter 
de pl o ys, t he t hera p e utic dr u g is ma n uall y a d mi nistere d t hr o u g h t he micr o cat heter t o t he 
s u prac h or oi dal s p ace, usi n g a s yri n ge attac he d t o t he dr u g li ne of t he O x ul u mis ®  de vice. T he 
t hera pe utic dr u g s h o ul d o nl y be a d mi nistere d aft er vis ual c o nfir mati o n t hat t he micr ocat h eter 
was s uccessf ull y de pl o ye d i n t he s u prac h or oi dal s pace.  T his vis ual c o nfir m ati o n is e na ble d b y 
t he ill u mi nati o n of t he micr ocat h eter. 
T he O x ul u mis ®  is c o m prise d of t he f oll o wi n g c o m p o ne nts (Fi g ure 4 ): 
• 
T he O x ul u mis ®  de vice b o d y c o nsists of t w o s u basse m blies, t he Micr ocat h eter H u b 
s u basse m bl y a n d t he Mai n S haft s u basse m bl y; a pr otecti ve ca p, tri g ger, s p ee d a dj ust me nt 
k n o b, a n d s pee d c o ntr ol acti vati o n pi n are p art of t he de vice b o d y.  
• 
A fle xi ble, ill u mi nate d micr ocat het er wit h a distal s oft ti p c o nfi g ure d f or s u prac h or oi d al 
de pl o y me nt.  
• 
A fi ber o ptic ca ble wit h a c o n nect or t hat attac hes t o a re m ote li g ht s o urce ( N o va E ye 
Me dical i L u mi n ™ Fi ber o ptic Ill u mi nat or) f or ill u mi nati o n of t he micr ocat heter.  

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• 
A micr ocat heter fl ui d li ne t hat ter mi nates i n a l o w dea d s pace L uer c o n nect or f or 
attac h me nt t o t he dr u g pr o d uct s yri n ge.  
• 
A n o pti o nal sterile, si n gle -use, dis p osa ble s yri n g e st o p, is pr o vi de d i n a se parate peel  
p o uc h i n t he O x ul u mis ®  pac ka g e. T he dis p osa ble s yri n ge st o p will n ot be utilize d as a part 
of t his cli nical trial.  
T he f oll o wi n g n o n -i n vesti gati o nal me dical de vices are re q uire d f or t he dr u g a d mi nistrati o n 
wit h t he O x ul u mis ® : 
1.  
Merit Me dical L uer s yri n ge, 2 5 0 µl ( 5 1 0 k i n U S; C E -mar ke d  i n E U) 
2.  
N o va E ye Me di cal i L u mi n ™ Fi ber o ptic Ill u mi nat or ( 5 1 0 k i n U S; C E -mar k e d  i n E U) 
T he O x ul u mis ®  de vice is pac ka g e d i n a p o uc h. T h e p o uc h is seale d t o create a sterile b arrier. 
T he O x ul u mis ®  de vice is sterilize d via e -b ea m irra diati o n b y a t hir d -part y v e n d or. T he 
p o uc he d pr o d u ct is la bele d a n d place d i nt o a la bel e d si n gle pr o d uct b o x.  Wit h t he pr o d uct 
b o x, a n I F U ( Versi o n: O X U C T-1 0 2) is pr o vi de d. T he la n g ua ge re q uir e me nt of eac h c o u ntr y 

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will be met bef ore distri b uti o n i n t hat c o u ntr y. T his pr o d uct will be pr o vi de d t o me dical 
pr ofessi o nals o nl y.  
La bels f or t he O x ul u mis ®  de vice i ncl u de o uter b o x la bels, a p o uc h la bel, a n d t he I F U 
(Versi o n: O X U C T -1 0 2 ). 
6. 1. 2. 4  I nstr ucti o ns f or I nst all ati o n a n d Use 
I nstr ucti o ns f or use of O x ul u mis®  are pr o vi de d i n t he I F U (Versi o n: O X U C T -1 0 2 ). 
6. 1. 2. 5  S u m m ary of Necess ary Tr ai ni n g a n d E x perie nce  
T he  O x ul u mis ®  de vice  is i nte n de d f or use o nl y b y certifie d me dical practiti o ners trai ne d i n 
reti nal disease ma n a ge m e nt. T hese s pecialize d p h ysicia ns s h o ul d be a de pt i n i ntra oc ular dr u g 
a d mi nistrati o n a n d i n t he use of ma n ual o p ht hal mi c i nstr u me nts. T he s p o ns or or desi g nees 
will perf or m a tr ai ni n g o n t he de vice pr oce d ures b ef ore st u d y i n vesti gat ors use t he O x ul u mis ®  
de vice i n t his cli nical trial.  
6. 1. 2. 6  O x ul u mis ®  Acc o u nt a bility  
T he i n vesti gati o nal de vices will n ot be distri b ute d t o t he i n vesti gati o n site u ntil all a gree me nts 
bet wee n t he i n v esti gat or a n d t he s p o ns or are fi nali ze d a n d I R B/I E C a p pr o v al has bee n 
o btai ne d.  
All i n vesti gati o nal de vices s hall be ke pt i n a sec ure place u n d er a p pr o priate st ora ge 
c o n diti o ns.  
Use of i n vesti gati o nal de vices will be l o g ge d i n a se parat e acc o u nta bilit y f or m st ore d i n t he 
I n vesti gat or Site File a n d be re vie we d at eac h m o nit ori n g visit.  
T he i n vesti gati o nal de vices ma y o nl y be use d i n t his cli nical trial a n d acc or di n g t o t he 
pr ot oc ol. T he  u n mas ke d i n vesti gat or or a n u n mas k e d a ut h orize d d esi g nee s hall kee p rec or ds 
d oc u me nti n g t he recei pt, use, ret ur n, a n d dis p osal of t he i n vesti gati o nal de vices.  
U n use d pr o d ucts are acc o u nte d f or a n d ret ur ne d t o t he S p o ns or or t heir desi g nee f or 
destr ucti o n or  are destr o y e d l ocall y u p o n a gree me nt wit h a n d a p pr o val fr o m t he s p o ns or or 
t heir desi g nee. 

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6. 2  
Oz ur de x ®   
Oz ur de x ®  is a n i ntra vitreal i m pla nt c o ntai ni n g 0. 7 m g  de xa met has o ne i n t he N o va d ur ®  s oli d 
p ol y mer s ustai ne d -rel eas e bi o de gra d a ble  dr u g d eli ver y s yste m. Oz ur de x ®  is prel oa de d i nt o a 
si n gle-use, D D S ®  a p plicat or t o facilitate i njecti o n of t he r o d -s ha p e d i m pla nt directl y i nt o t he 
vitre o us. T he N o va d ur ®  s yste m c o ntai ns p ol y ( D, L-lacti de-c o-gl yc oli de) P L G A i ntra vitreal 
p ol y mer matri x wit h o ut a preser vati ve. T he P L G A matri x sl o wl y de gra des t o lactic aci d a n d 
gl yc olic aci d. Oz ur de x vi a I V T d eli ver y wit h its a p plicat or is U S F D A -a p pr o ve d f or t he 
treat me nt of i) mac ular e de ma f oll o wi n g bra n c h reti nal vei n occl usi o n ( B R V O) or ce ntral 
reti nal vei n occl usi o n ( C R V O), ii) n o n-i nfecti o us u veitis affecti n g t he p osteri or se g me nt of t h e 
e ye, a n d iii) D M E  i n pati e nts. I n t he E U, Oz ur de x is a p pr o ve d f or i) vis ual i m pair me nt d ue t o 
D M E w h o are pse u d o p ha kic or t hat are c o nsi dere d i ns ufficie ntl y res p o nsi ve t o, or u ns uita ble 
f or n o n-c ortic oster oi d t hera p y, ii) mac ular e de ma f oll o wi n g eit her Bra nc h R eti nal Vei n 
Occl usi o n ( B R V O) or Ce ntral Reti nal Vei n Occl usi o n ( C R V O), a n d iii) i nfla m mati o n of t he 
p osteri or se g me nt of t he e ye pres e nti n g as n o n -i nf ecti o us u veitis. 
F or t his cli nical trial, Oz ur de x ®  will be a d mi nistere d i ntra vitreall y acc or di n g t o its a p pr o ve d 
r o ute a n d met h o ds of a d mi nistrati o n. N o ot her f or m of a d mi nistrati o n  or pr oce d ural varia nt  is 
all o we d. 
6. 3  
Lifest yle C o nsi der ati o ns  
N o s pecial lifest yle c o nsi derati o ns or restricti o ns are re q uir e d f or p artici pati o n i n t his cli nical 
trial. 
6. 4  
Scree n F ail ures  
A scree n fail ure occ urs w he n a s u bject w h o h as c o nse nte d t o partici pate i n t he cli nical trial is 
n ot s u bse q ue ntl y e nr olle d i n t he trial. A mi ni mal set of scree n fail ure i nf or mati o n is re q uire d 
t o e ns ure tra ns p are nt r e p orti n g of scree n fail ure s u bjects t o meet t he C O N S O R T p u blis hi n g 
re q uire 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 S A E. 
S u bjects, w h o  d o n ot meet eli gi bilit y criteria  at t he i nitial scree ni n g visit  b ut base d o n t he 
in vesti gat or ’s j u d geme nt are li kel y t o meet all  eli gi bilit y criteria wit hi n t he scree ni n g wi n d o w 
of u p t o 3 0 da ys  (e. g., if arterial h y p erte nsi o n is a b o ve pr ot oc ol-defi ne d t hr es h ol ds at t he 

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i nitial scree ni n g visit), ca n be re-assesse d wit hi n t he scree ni n g wi n d o w  a n d e nr olle d if 
eli gi bilit y criteria are s u bse q ue ntl y m et. 
I n di vi d uals w h o d o n ot meet t he criteri a f or p arti ci pati o n i n t his cli nical trial (scree n fail ure) 
ma y be res cree ne d o nce after faili n g t he i nitial scree ni n g. T he rescree ni n g ca n occ ur at a n y 
ti me after t he reas o n f or scree n fail ure is a d dresse d. Rescree n ed s u bjects s h o ul d be assi g ne d a 
ne w s u bject n u m ber , si g n a ne w I C F f or t he rescree ni n g e ve nt, a n d will nee d t o recei ve a 
c o m plete a ne w scree ni n g visit.  
7  
St u d y I nter ve nti o n(s) a n d C o nc o mit a nt T her a pies  
7. 1  
Dr u g Pre p ar ati o n, H a n dli n g St or a ge, a n d Acc o u nt a bilit y  
O nl y s u bjects e nr olle d i n t his cli nical trial ma y recei ve st u d y i nter ve nti o n, a n d o nl y 
a ut h orize d site staff ma y s u p pl y, pre pare, or a d mi nister st u d y i nter ve nti o n.  
All st u d y  treat me nts m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d 
( ma n ual or a ut o mat e d) area i n acc or da n ce wit h t he la bele d st ora g e c o n diti o ns wit h access 
li mite d t o t he i n vesti gat or a n d a ut h orize d site staff. 
T he i n vesti gat or or del e g ate ( e. g., t he p har mac y) are res p o nsi ble f or st u d y i nter ve nti o n 
acc o u nta bilit y, rec o nciliati o n, a n d rec or d m ai nte na nce ( i.e., recei pt, rec o n ciliati o n, a n d fi nal 
dis p ositi o n rec or ds).  
U n use d pr o d ucts are acc o u nte d f or a n d ret ur ne d t o t he S p o ns or or t heir desi g nee f or 
destr ucti o n or destr o ye d l ocall y u p o n a gree me nt wit h a n d a p pr o val fr o m t he s p o ns or or t heir 
desi g nee.  
7. 1. 1  O X U -0 0 1  
O X U -0 0 1 is descri be d i n Secti o n  6. 1 . Refer t o t he O X U C T-1 0 2 P har mac y Ma n ual f or 
detaile d i nstr ucti o ns o n st ora ge, pre parati o n, ha n dli n g, a d mi nistrati o n, acc o u nta bilit y, a n d 
destr ucti o n.  
7. 1. 1. 1  P ac k a gi n g a n d L a beli n g  
O X U -0 0 1 is pr o vi de d 
 
 
i n a si n gle-d ose, 2 m L vi al f or rec o nstit uti o n wit h sterile Water f or I njecti o n ( W FI). T h e 
O X U -0 0 1 dr u g pr o d uct will be rec o nstit ute d t o pr o vi de t w o d ose le vels as eit her a D M A 

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2 5 m g/ ml ( 1. 5 m g/ 6 0 µl or 0. 7 5 m g / 3 0 µl, mi d-d ose a n d l o w d ose D M A res pecti vel y) re q uiri n g 
rec o nstit uti o n wit h 1 m L of W FI or a D M A 5 0 m g/ ml c o nce ntrati o n ( 3 m g/ 6 0 µl) re q uiri n g 
rec o nstit uti o n wit h 0. 5 m L of W FI. T h e O X U-0 0 1 la beli n g c o m plies wit h l ocal re g ulati o ns f or 
t he la beli n g of a n i n vesti gati o nal dr u g/ me dici nal pr o d uct (f or a detaile d descri pti o n of 
rec o nstit uti o n a n d dr u g h a n dli n g see f urt her i nf or mati o n i n t he O X U C T -1 0 2 p har mac y 
ma n ual) . 
7. 1. 1. 2  St or a ge  
After ma n ufact uri n g, O X U -0 0 1 is st ore d b y a G o o d Ma n ufact uri n g Practice ( G M P) st ora ge 
facilit y a n d s hi p pe d o n dr y ice f or recei pt b y t he res pecti ve cli nical site pri or t o a s u bject’s 
sc he d ule d a d mi nistrati o n date. U p o n recei pt at t he cli nical site, O X U-0 0 1  s hall be st ore d 
fr oze n at -2 0° C ( -4° F) wit h a te m perat ure of t he st ora ge l ocati o n c o ntr olle d t o ± 1 0° e ntere d 
i nt o i n ve nt or y a n d ma na ge d acc or di n g t o p har mac y sta n dar d o perati n g pr o ce d ures or 
c o m para ble u ntil rec o nstit ute d a n d dis pe nse d f or s u bject a d mi ni strati o n. 
7. 1. 1. 3  Pre p ar ati o n  
Rec o nstit uti o n of O X U -0 0 1 s hall be perf or me d b y q ualifie d cli nical pers o n nel i n acc or da nce 
wit h t he O X U C T -1 0 2 P har mac y M a n ual base d o n t he prescri b e d d osi n g c o nce ntrati o n f or t h e 
s u bject. Rec o nstit uti o n of t he l y o p hilize d O X U-0 0 1 dr u g pr o d uct s hall be perf or me d usi n g 
sta n dar d ase ptic a n d sterile tec h ni q ues. If a vial is o bser ve d t o be da ma ge d a n d/ or lea ki n g, 
n otif y t he i n vesti gat or a n d s p o ns or, a n d d o n ot dis pe nse t he O X U -0 0 1 dr u g pr o d uct f or 
a d mi nistrati o n t o t he s u bject.  
7. 1. 1. 4  A d mi nistr ati o n  
T he s u prac h or oi dal i njecti o n pr oce d ure s hall be carrie d o ut u n der c o ntr olle d ase ptic 
c o n diti o ns as esta blis he d f or f or ms of i ntra oc ular dr u g t hera pies, e. g., i ntra vitreal dr u g 
a d mi nistrati o n  a n d i n cas e of t he O X U -0 0 1 C o njI ncisi o n  V aria nt wit h a n i ncisi o n of t he 
c o nj u ncti va/te n o ns o nl y t o a d mi nister O X U -0 0 1 . A de q uate a nest hesia (t o pical or i njecti o n) 
a n d a br oa d -s pectr u m micr o bici de (e. g., p ol y vi d o ne-i o di ne, or c hl or h e xi di ne) are re q uire d t o 
be a p plie d t o t he peri o c ular s ki n, e yeli d , a n d o c ular s urface pri o r t o t he a d mi nistrati o n 
pr oce d ure.  
O X U -0 0 1 s hall be a d mi nistere d s u prac h or oi dall y usi n g t he O x ul u mis ®  i n acc or da n ce wit h t he 
O x ul u mis ®  I F U ( Versi o n O X U C T-1 0 2) . O X U-0 0 1 s hall be a d mi nistere d o nl y b y cli nical trial 

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pers o n nel w h o ha v e recei ve d f or mal trai ni n g fr o m t he s p o ns or ( or desi g ne e) o n t he 
pre parati o n a n d use of t h e O x ul u mis de vice.  
F oll o wi n g t he s u prac h or oi dal i njecti o n of O X U -0 0 1, m o nit or t he s u bject f or ele vati o n i n I O P 
f or 6 0 mi n a n d f or e n d o p ht hal mitis i n t he visits f oll o wi n g dr u g a d mi nistrati o n, i.e., Da y 1 a n d 
Da y 7. A d diti o nall y, c hec k f or e vi de n ce of dr u g deli ver y t o t he wr o n g oc ular c o m part me nt 
(e. g., t he t hera pe utic a ge nt i n t he vitre o us h u m or or s u bc o nj u ncti val) after t he a d mi nistrati o n. 
S u bjects s h o ul d be i nstr ucte d t o re p ort a n y s y m pt o ms s u g gesti ve of e n d o p ht hal mitis wit h o ut 
dela y.  
O X U -0 0 1 a d mi nistere d wit h t he O x ul u mis ®  is i nte n de d f or o n e-ti me use a n d a d mi nistrati o n t o 
a si n gle e ye o nl y. Dis p ose of t he dr u g vial a n d de vice as me dical waste i m me diatel y after use.  
7. 1. 2  Oz ur de x ®   
Refer t o a n d a d mi nister Oz ur de x ®  acc or di n g t o t h e f ull prescri bi n g pr o d uct i nsert 
acc o m pa n yi n g t he dr u g.  
7. 2  
Assi g n me nt t o St u d y I nter ve nti o n  
7. 2. 1  P art A  
Part A will i ncl u de treat me nt-naï ve or D M E  s u bj ects pre vi o usl y treate d i n t he st u d y e ye wit h 
I V T a nti-V E G F ( n = 1 8) . N o mi ni m u m n u m ber of treat me nt -naï ve s u bj ects is fi xe d i n Part A, . 
S u bjects will be ra n d o mize d usi n g  a 1: 1 rati o, t o r ecei ve eit her t he mi d-d os e  O X U -0 0 1  
(treat me nt ar m A 1, n = 9) or  t he hi g h d ose O X U -0 0 1  (treat me nt ar m A 2, n = 9) acc or di n g t o a 
ce ntral r a n d o mizati o n sc he me pr o vi de d b y a n i nteracti ve v oice res p o ns e s yste m 
(I V R S)/i nteracti ve w e b res p o nse s yste m (I W R S) t o t he desi g nate d st u d y p h ar macist ( or 
q ualifie d desi g nee).  If s u bjects ha ve bee n  ra n d o mize d b ut t he st u d y treat me nt ca n n ot be 
a d mi nistere d, t hese s u bjects will be re place d  t o reac h a p pr o xi mat el y 1 8  treate d s u bjects i n 
Part A . E nr oll me nt of pre vi o usl y treate d a n d treat me nt -naï ve s u bjects will be c o m petiti ve  u ntil 
t he tar gete d s u bj ect n u m ber is reac he d. 
7. 2. 2  P art B  
A p pr o xi matel y 1 1 0 s u bjects will be ra n d o mize d i n a 2: 2: 1 rati o t o recei ve eit her O X U -0 0 1 
D ose 1 ( mi d -d ose, 1. 5 m g, Ar m B 1), O X U -0 0 1 D ose 2 ( d ose le vel of O X U -0 0 1 eit her 3. 0 m g, 
or 0. 7 5 m g , de pe n di n g o n Wee k 6 s afet y r e vie w, Ar m B 2), or I V T Oz ur de x ® (0. 7 m g ) 

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( Ar m B 3) acc or di n g t o a ce ntral r a n d o mizati o n sc he me pr o vi de d b y a n i nteracti ve v oice 
res p o nse s yste m (I V R S)/i nteracti ve w e b res p o ns e s yste m (I W R S) t o t he desi g nate d st u d y 
p har macist ( or q u alifie d desi g nee).  S u bjects will be ra n d o mize d after t he treati n g p h ysicia n 
has ma de a d ecisi o n o n t he l ocati o n of t he 1st treat me nt sessi o n (cli nic, pr oce d ure, or o perati n g 
r o o m) f oll o wi n g a n e x pert j u d ge me nt o n t he e x pecte d pr oce d ural c o m ple xit y  (f or g ui da nce o n 
t he c o m ple xit y assess me nt see Secti o n 1 2. 4 ). N o s ha m pr oce d ure will be p erf or me d f or t he 
c o nj u ncti val/te n o n i ncisi o n i n case of ra n d o mizati o n t o t he Oz ur de x®  treat me nt ar m. 
I n Part B, b ot h treat me nt-naï ve a n d a nti-V E G F pre vi o usl y treate d s u bjects (i n t he st u d y e ye) 
will be e nr olle d . E nr oll me nt of pre vi o usl y treate d a n d treat me nt -n aï ve s u bj ects will be 
c o m petiti ve, wit h a t least 5 5 s u bjects bei n g treat m e nt-naï ve i n t he st u d y e ye. E nr oll me nt of 
s u bjects t hat are a nti-V E G F pre vi o usl y treate d i n t he st u d y e ye will st o p o nce 5 5 s u bjects wit h 
pre vi o us a nti -V E G F treat me n t i n t he st u d y e ye are ra n d o mize d t o all o w reac hi n g t he f ores ee n 
n u m ber of treat me nt -naï v e s u bjects . S u bjects will be stratifie d bas e d o n t heir a nti -V E G F 
treat me nt hist or y (see Secti o n 4. 1. 1 ). If s u bjects h a ve bee n  ra n d o mize d b ut t he st u d y 
treat me nt ca n n ot b e a d mi nistere d, t hese s u bjects will be re place d t o r eac h a p pr o xi matel y 
1 1 0  treate d s u bjects i n Part B . 
7. 3  
M as ki n g  
P art A : T his part of t he trial has  an o pe n -la bel, si n gle-d os e desi g n  wit h 1: 1 ra n d o mizati o n t o 
o ne of t w o treat me nt  ar ms . All s u bjects will recei v e i n vesti gati o nal treat me nt. 
P art B : T his Part of t he trial has  a mas ke d, acti ve c o m parat or, si n gle -d ose  desi g n wit h  a 2: 2: 1 
ra n d o mizati o n t o o ne of t hree tr eat me nt ar ms. I n t his part of t he trial, t he f oll o wi n g r oles are 
a p plie d t o s u p p ort t he scie ntific vali dit y of t he trial . 
A.  R oles  full y m as ke d  t o treat me nt assi g n me nt. 
1.  
S u bjects : 
S u bjects will be  f ull y mas ke d t o t he st u d y i nter ve nti o n. Assi g n me nt t o treat me nt 
ar ms will o nl y be discl ose d after t he e n d of t h e tri al (after all s u bjects ha v e 
c o m plete d t he Wee k 5 2 visit). T o li mit t he treat me nt b ur de n f or s u bjects, n o s ha m 
treat me nt f or t he n o n -assi g ne d treat me nt m o dalit y (I V T i m pla nt or s u prac h or oi dal 
a d mi nistrati o n) will be perf or me d. T his is c o nsi dere d acce pta bl e as re gar dl ess of t he 
ra n d o mize d tr eat me nt, s u bjects ha d ne ver recei ve d a n y of t he p ote ntial treat me nts 
bef ore  i n t he st u d y e y e p er eli gi bilit y cr iteria. T he u n mas ke d treat me nt tea m is 

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e x pecte d t o c o ver t he st u d y treat me nt a n d a n cillar y  material s u ntil t he s u bject is 
p ositi o ne d i n t he treat me nt c hair a n d t he n a gai n after c o m pleti o n of t he pr o ce d ure  
w he n t he s u bject lea ves t he treat me nt r o o m . 
F or mas ki n g p ur p oses, t he c h oice of t he pr oce d ural setti n g (i.e., t he selecti o n of t he 
treat me nt alter n ati ve s h o w n see Ta ble 4 ) will be ma de bef ore ra n d o mizati o n , a n d it 
will  n ot  be  c ha n ge d e v e n i n case a s u bject i n Part B is ra n d o mize d t o recei ve 
Oz ur de x ® . 
T he  pr oce d ure alter nati v e N o. 2  of  direct l y m o vi n g t o a n O X U -0 0 0 1  C o njI ncisi o n  
Pr oce d ural Varia nt  i n a n s ur gicall y e q ui p pe d pr o ce d ure or o perati n g r o o m (see Ta ble 
4 ) will n ot carr y a n  i n crease d ris k f or a s u bjects g etti n g hi nts t o t heir ra n d o mizati o n 
t o t he Oz ur de x®  or o ne of t he O X U -0 0 1 treat me nt ar ms, as t here will  be  o nl y o ne 
st u d y treat me nt i n t his trial. 
I n case of n o n -c o m pleti o n of t he O X U -0 0 1 Sta n dar d  Pr oce d ural varia nt  (i. e., 
Alter nati ve N o. 3) , resc h e d uli n g of  st u d y treat me nt as i n a s ur gicall y e q ui p pe d 
pr oce d ure r o o m or a n o p erati n g r o o m  all o wi n g t h e O X U -0 0 0 1 C o njI n cisi o n  
Pr oce d ural Varia nt ma y pr o vi de hi nts f or t he s u bject i n res pect t o t he assi g n me nt, 
b ut still t he ra n d o mize d O X U -0 0 1 d ose w o ul d re mai n c o m pletel y mas ke d.  S u b gr o u p 
a nal yses f or t h e t hree differe nt sc h e d uli n g o pti o ns ( N o. 1-N o 3) will  be perf or me d.  
2.  
F ull y Mas ke d s ite staff assessi n g mai n e n d p oi nts: 
T he s ite staff w h o assess es  t he N EI-V F Q 2 5, t h e S u bject E x perie nce Assess me nt 
a n d best c orrecte d vis u al ac uit y  ( E T D R S) will be f ull y mas ke d . T hese i n di vi d uals 
will ha ve n o access t o ot her st u d y assess me nt s or trial data n or  t o t he e C R F a n d m ust 
n ot be i nf or me d res c he d uli n g of t he st u d y treat me nt . O utc o mes of t hese assess me nts 
will be e ntere d i nt o t he e C R F b y ot her site staff. 
3.  
F ull y Mas ke d C R C Rea ders : 
T he f ull y mas ke d rea ders at t he C R C will o nl y ha ve access t o S D -O C Ts f or 
assessi n g t he C S T. Ot her trial i ma gi n g, e. g., C F P , 4 Wi de -Fi el d I R Pl us i ma ges  or 
peri p heral O C T ma y pr o vi de hi nts t o treat me nt assi g n me nt a n d will be a nal yze d  
se parat el y wit h meas ures i n place t o sec ure mas ki n g, as detaile d i n Secti o n B 
bel o w) . 
 

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B.  R oles m as ke d t o tre at me nt assi g n me nt  b ut wit h ris k of i na d verte ntl y getti n g hi nts t o 
treat me nt assi g n me nt. 
As t he I V T O z ur de x i m pla nt or t he s u prac h or oi dal dr u g ble b of O X U -0 0 1 ma y be vis ualize d 
d uri n g s o me of t he st u d y assess me nts, e. g., i n direct o p ht hal m osc o p y, or peri p heral O C T 
i ma gi n g, it ca n n ot be e xcl u de d, t hat t he f oll o wi n g r oles ma y get hi nts t o t he i n di vi d uall y 
assi g ne d st u d y i nter ve nti o n. H o we ver, as t hese r oles ha ve n o access t o t he treat me nt 
assi g n me nt of a n i n di vi d ual s u bject,  t he y will re m ai n f ull y mas ke d t o t he d ose le vel 
assi g n me nt i n t he O X U -0 0 1 ar ms.  
1.  Mas ke d Site Staff perf or mi n g st u d y assess me nts, i ncl u di n g o p ht hal mic assess me nts: 
Site staff i n v ol ve d i n perf or mi n g o p ht hal mic assess me nts a n d i ma gi n g re vie ws  f or 
safet y p ur p oses, m a y see hi nts t o t he st u d y i nter ve nti o n b y detecti n g t he I V T Oz ur de x 
i m pla nt or t he s u prac h or oi dal dr u g ble b o n oc ular  i ma gi n g. 
If me m bers of t hese e v al uati o n tea ms w o ul d i na d verte ntl y get i nf or mati o n o n t he 
treat me nt assi g n me nt, t his i nf or mati o n m ust n ot  be e xc h a n ge d wit h ot her c ollea g ues. 
T his als o i ncl u des t he i nf or mati o n a b o ut a nee d f or a 2n d treat me nt sessi o n, i n case t he 
first treat me nt sessi o n i n a n i n-cli nic setti n g ca n n ot be c o m plete d.  
P ote ntiall y  u n mas ki n g i nf or mati o n , w hic h is pi v otal  f or ma na gi n g safet y e ve nts, is 
rec o m me n de d t o b e s hare d wit h t he u n mas ke d st u d y tea m. T h e u n mas ke d st u d y tea m 
w o ul d  t he n c o nti n ue t he ma na ge me nt of p ote ntial safet y e ve nts or c o m plicati o ns.  
2.  Staff at C R C i n v ol ve d i n assess me nt of i ma gi n g ot her t ha n S D -O C T :  
T his part of t he C R C staff will be m as ke d t o t he tr eat me nt assi g n me nt b ut ma y 
i na d verte ntl y get hi nts o n treat me nt assi g n me nt ( Oz ur de x or O X U-0 0 1) fr o m t he 
ac q uire d i ma gi n g.  
C.  R oles mas ke d t o O X U -0 0 1 d ose le vel b ut n ot t o treat me nt assi g n me nt . 
1.  I ma gi n g te c h nicia n at t he i n vesti gati o nal sites: 
S pecificall y f or  a nteri or s e g me nt i ma gi n g, a n d f or  peri p heral i ma gi n g of t he O X U -0 0 1 
ble b i njecti o n, t he i ma gi n g tec h nicia ns will ha ve t o recei v e i nf or mati o n o n t he re gi o n 
of O X U -0 0 1/ O x ul u mis i nserti o n b y t he u n mas ke d treati n g tea m. As s uc h, t he i ma gi n g 
tec h nicia ns will be u n mas ke d t o t he treat me nt ( Oz ur de x or O X U-0 0 1) b ut n ot t o t he 
O X U -0 0 1 d ose le v el.  T his r ole m ust n ot tal k t o ot her me m bers of t he mas ke d 
e val uati o n tea m or t o f ull y mas ke d r oles a b o ut t he treat me nt assi g n me nt.  

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D.  R oles u n mas ke d Site t o treat me nt assi g n me nt i ncl u di n g O X U -0 0 1 d ose le vel . 
1.  I P ha n dli n g a n d pre parati o n pers o n nel: 
T he tea m i n v ol ve d i n pre pari n g t he treat me nt ( e. g. , dr u g rec o nstit uti o n) a n d 
pre parati o n f or i njecti o n . 
2.  Treati n g p h ysicia n a n d s u p p orti n g r oles : 
T he treati n g reti nal p h ysicia n a n d s u p p orti n g tea m assisti n g i n t he treat me nt 
a d mi nistrati o n a n d p ost -treat me nt f oll o w-u p. Acti vities i ncl u de dr u g a d mi nistrati o n, 
p ost -i nter ve nti o n safet y m o nit ori n g f or 6 0 mi n utes, t he c o m pleti o n of t he P h ysicia n’s 
assess me nt of t he a d mi nistrati o n pr oce d ure a n d  d eci di n g o n a n d a p pl yi n g f oll o w -o n 
treat me nt ( b y t he reti nal p h ysicia n). 
3.  S p o ns or tea m  or dele gat es  tas ke d wit h o n-site or re m ote de vice tr ai ni n g a n d pr oce d ure 
s u p p ort: 
S p o ns or e m pl o yees or dele gate pers o n nel will be o n -site f or all st u d y i nter ve nti o ns. 
T his gr o u p nee ds t o k n o w all i nf or mati o n a b o ut t he pla n ne d treat me nt t o f ull y s u p p ort 
t he treati n g p h ysicia n (i n cl u di n g t he O X U-0 0 1 d ose le vel).  
S p o ns or, C R O, a n d ot her r oles wit h res pect t o mas ki n g will be detaile d i n t he Data 
I nte grit y/ Mas ki n g Pla n. Site staff, C R O, ot her ve n d ors, a n d S p o ns or  staff will be trai ne d o n 
t heir r oles pri or t o t he start of ra n d o mizati o n of s u bjects. 
T he I V R S/I W R S will be pr o gra m me d wit h mas k -brea ki n g i nstr ucti o ns. I n case of a n 
e mer ge n c y, t he i n vesti gat or  or e xter n al p h ysicia ns, w h o ma y re q u est u n mas ki n g i n e mer ge nc y 
sit uati o ns ha ve  t he s ole res p o nsi bilit y f or deter mi ni n g if u n mas ki n g of a s u bjects’ i nter ve nti o n 
assi g n me nt is warra nte d. S u bject safet y m ust al wa ys be t he first c o nsi derati o n i n ma ki n g s uc h 
a deter mi nati o n . If t h e i n vesti gat or deci des t hat u n mas ki n g is warra nte d, t h e i n vesti gat or ma y, 
at t he i n vesti gat or’s discreti o n, c o ntact t he s p o ns or t o disc uss t he sit uati o n pri or t o u n mas ki n g 
a s u bject’s i nter ve nti o n assi g n me nt u nless t his c o ul d dela y e mer g e nc y tr eat me nt f or t he 
s u bject. If a s u bject’s i nter ve nti o n assi g n me nt is u n mas ke d, t he s p o ns or m ust be n otifie d 
wit hi n 2 4  h o urs of t his occ urre nce. T he d ate a n d reas o n f or t he u n mas ki n g m ust be rec or de d  
i n t he s o urce d oc u m e ntati o n a n d case re p ort f or m ( C R F), as a p plica ble. 
7. 4  
St u d y I nter ve nti o n C o m pli a nce  
T he i n vesti gat or ( u n mas k e d i n vesti gat or i n Part B) will a d mi nister t he st u d y i nter ve nti o n. T he 
date a n d ti me of eac h  tr eat me nt sessi o n a n d fi nall y of t he  d ose a d mi nistere d will be rec or de d 

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i n t he s o urce d oc u m e nts. T he st u d y i nter ve nti o n a n d st u d y s u bject i de ntificati o n will be 
c o nfir me d at t he ti me of d osi n g b y a me m ber of t he st u d y site staff ot her t ha n t he pers o n 
a d mi nisteri n g t he st u d y i nter ve nti o n.  
7. 5  
D ose M o dific ati o n, F oll o w -o n Tre at me nt, a n d Tre at me nt of D i a betic Reti n o p at h y 
C o m plic ati o ns  
7. 5. 1  D ose Le vel C o nfir m ati o n i n  P art B  Tre at me nt Ar m B 2  
T he ra n d o mize d o pe n -la bel Part A of t his trial will treat 1 8 s u bjects wit h s u prac h or oi d al 
s ustai ne d-rele ase O X U -0 0 1. S u bjects will be ra n d o mize d t o  recei ve eit her mi d -d ose ( Ar m A 1 
1. 5 m g/ 6 0 µl) or  hi g h d ose ( Ar m A 2 3. 0 m g/ 6 0 µl)  O X U -0 0 1 . S h ort-ter m o utc o mes wit h a f oc us 
o n safet y i n Part A will be e val uat e d o nce all 1 8  treate d s u bjects h a ve c o m plete d t he Wee k 6 
visit.  
T he f oc us of t h e e val u ati o n will be o n t he occ urre nce of oc ul ar A Es, A E SIs, a n d S A Es. As t he 
o nset of cli nicall y mea ni n gf ul i ncreas es i n I O P is us uall y see n wit hi n u p t o Wee k 6 after 
oc ular a d mi nistrati o n of ster oi ds, a s pecific f oc us will be o n I O P i ncrea se p er d ose gr o u p. 
Cate g ories of e v al uati o n will i ncl u de b ut are n ot li mite d t o : 
1.  S u bjects wit h at least 1 0 m m H g i ncrease after treat me nt a d mi nistrati o n . 
2.  S u bjects wit h I O P of at least 3 0 m m H g.  
T he e val uati o n will be disc usse d wit h t he D M C. Base d o n t he D M C rec o m me n dati o n, t he 
s p o ns or will t he n, f or t he d ose le vel i n treat me nt ar m B 2, eit her:  
1.  C o nfir m d ose le vel t o be 3. 0 m g D M A a d mi nistere d i n 6 0 µ l, or  
2.  Assi g n t he l o wer d ose le vel of 0. 7 5 m g  D M A a d mi nistere d i n 3 0 µl  
All ot her desi g n ele me nts of Part B will n ot be i m pacte d.  
7. 5. 2  F oll o w -o n Tre at me nt  
S u bjects will be f oll o we d wit h re g ular visits t o assess t he safet y a n d t he c o urse of vis ual a n d 
a nat o mic o utc o mes. Starti n g at t he Wee k 1 2 visit, s u bjects will be e val uate d a gai nst 
pres pecifi e d criteria i n dicati n g t he nee d f or f oll o w -u p treat me nt ( i.e., i n dicati n g t he e n d of t he 
c urre nt treat me nt i nter val). Criteria are as f oll o ws:  

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1.  
At least 7 5 µ m t hic ke ni n g i n C S T o n S D -O C T c o m pare d t o best C S T val ue si nce t he 
baseli ne visit, Visit 2, Da y 0 ; or  
2.  
A decrease i n B C V A of > 1 0 letters ( E T D R S) fr o m t he best ac hie ve d B C V A si nce t he 
baseli ne visit, Visit 2, Da y 0, t hat, i n t he o pi ni o n of t he i n vesti gat or, is d ue t o t he 
w orse ni n g of D M E.  
F or s u bjects s h o wi n g n o re d ucti o n of e d e ma or n o i m pr o ve me nt of B C V A  after Visit 2, Da y 0 , 
t he baseli ne visit will be c o nsi dere d t he best C S T or B C V A val ue. 
T he C S T val ues  t o i nf or m t he e val uati o n of t he  f oll o w-o n treat me nt will be deri ve d fr o m t he 
S D -O C T o ut p uts ge nerat e d at t he site. I n Part B, t he mas ke d (e val uati o n) t ea m will re vie w 
C S T a n d B C V A a n d will i nf or m t he u n mas ke d treati n g i n vesti gat or. T he u n mas ke d treati n g 
i n vesti gat or will t he n select t he a p pr o priate f oll o w-o n treat me nt . 
If acc or di n g t o t he assess me nt of t he a b o ve criteri a ( b y a mas k e d i n vesti gat or i n Part B), t he 
nee d f or a d mi nistrati o n of f oll o w -o n treat me nt is i n dicate d, s u bjects will be ma na ge d 
acc or di n g t o l ocal sta n dar d of care f or t he rest of t he st u d y d urati o n. Sta n dar d of care 
treat me nts ma y i ncl u de I V T a nti-V E G F, oc ular I V T ster oi ds, or ot her n o n -i n vesti gati o nal 
treat me nts. Treat me nt wit h a p ort deli ver y s yste m d uri n g partici pati o n i n t his trial is f or bi d de n 
d ue t o t he c o m ple xit y of t he s ur gical a d mi nistrati o n pr o ce d ure a n d p ost a d mi nistrati o n 
f oll o w-u p a n d care.  
I n Part B, w he n f oll o w -o n treat me nt criteria are m et base d o n mas ke d assess me nt, t he 
u n mas ke d  i n vesti gat or will deter mi ne t he ki n d of f oll o w-o n treat me nt t o be a d mi nistere d  (e. g., 
I V T a nti-V E G F treat me nt, I V T ster oi d, or ot her) c o nsi deri n g t he treat me nt hist or y a n d t he 
res p o nse t o t he st u d y treat me nt recei ve d. F or t his p ur p ose , t he o utc o me of t he B C V A a n d C S T 
assess me nts are s h are d wit h t he u n mas ke d i n vesti gat or tas ke d wit h t he treat me nt of s u bjects. 
After recei vi n g t he first f oll o w -o n treat me nt i n t he st u d y e ye, s u bjects will c o nti n ue o n t he 
re g ular visit sc he d ule t hr o u g h t he E n d-of -St u d y visit at Wee k 5 2.  Patie nts will n ot be mas ke d 
t o t he assi g ne d f oll o w-o n treat me nt.  
7. 5. 3  Tre at me nt of Di a betic Reti n o p at h y Pr o gressi o n a n d C o m plic ati o ns  
A s u bject ma y recei ve treat me nt at a n y ti me if t he y e x perie n ce dia betic reti n o pat h y 
pr o gressi o n t hat re q uir es ur ge nt ma na g e me nt ( i.e., pr o gressi o n t o hi g h -ris k P D R or w orse) or 

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ma na ge me nt of dia b etic reti n o pat h y c o m plicati o ns ( v itre o us he m orr h a ge, n e o vasc ular 
gla uc o ma, iris ne o vas c ularizati o n, etc.).  
As per e x cl usi o n criteria N o. 1, N o. 5, a n d N o. 6 s u bjects wit h acti ve P D R, or a f oreseea ble 
nee d f or tr eat me nt of D R c o m plicati o ns ot her t ha n D M E are n ot eli gi ble f or partici pati o n i n 
t his trial. S uc h  D R c o m plicati o ns s h o ul d be ma na g e d bef ore a n y c o nsi derati o n of i ncl usi o n i n 
t he O X U C T-1 0 2 trial. A s u bject’s p ote ntial eli gi bilit y c o ul d be c hec k e d later  after t h e ti me 
i nter vals lai d o ut f or treat me nts i n t he e xcl usi o n criteria (see Secti o n 5 . 2). 
Treat me nt o pti o ns f or D R c o m plicati o ns  f or e nr olle d s u bjects ge nerall y i ncl u de pa nreti nal 
p h ot oc oa g ulati o n ( P R P) f or P D R, I V T a nti -V E G F, a n d/ or pars pla n a vitrect o m y. Treat me nt 
o pti o ns are best e val u ate d a n d deci de d b y a n u n m as ke d reti nal p h ysicia n t a ki n g i nt o 
c o nsi derati o n t he st u d y i nter ve nti o n a d mi nistere d. After recei vi n g t he treat me nt f or 
c o m plicati o ns i n t he st u d y e ye, s u bjects will c o nti n ue o n t he re g ular visit sc he d ule t hr o u g h t he 
E n d -of -St u d y visit at Wee k 5 2, a n d ma y als o r ecei ve f oll o w -o n treat me nt, if t he y met t he 
res pecti ve criteria (see S ecti o n 7. 5. 2 ). 
7. 6  
C o nti n ue d Access t o St u d y I nter ve nti o n after t he E n d of t he St u d y  
C o nti n ue d access t o treat me nt wit h O X U -0 0 1 will n ot be a vaila ble after t he c o m pleti o n of t he 
st u d y. Oz ur de x®  is a n a p pr o ve d a n d mar kete d pr o d uct a n d ca n b e access e d b y t he s u bject/ PI 
i n de pe n de ntl y. 
7. 7  
Tre at me nt of O v er d ose  
T he st u d y i ncl u des a si n gle treat me nt wit h st u d y i nter ve nti o n b y t he PI or dele gate. T he ris k 
of o ver d ose , d efi ne d f or O X U-0 0 1  as a d ose hi g h er t ha n t he hi g hest d ose defi ne d i n t he 
res pecti ve p art of t his trial, fr o m recei vi n g st u d y i nter ve nti o n is ver y l o w. I n t he u nli kel y case 
of a hi g her d os e of D E X As p here s®  bei n g a d mi nistere d, s u bjects will be m o nit ore d cl osel y f or 
t he e mer g e nce of si de effects s uc h as i ncreas e d I O P a n d cataract f or mati o n. A n y e mer gi n g 
si de effects will be ma na ge d base d o n t he cli nical discreti o n of t he i n vesti g at or a n d 
c o ns ultati o n wit h t he s p o ns or ( O x ular M e dical M o nit or).  
7. 8  
Pri or a n d C o nc o mit a nt T her a p y  
F or h o w t o re vie w c o n c o mita nt me dicati o n, please see Secti o n 9. 2. 6 . 

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I ntra nasal, i n hal e d, a n d t o pical (e xtr a-oc ular) gl uc oc ortic oi d me dicati o ns or sta ble s yste mic 
ster oi ds are all o we d. F or f urt her g ui da nce see als o Secti o n 7. 8. 1 . 
T he use of oc ular t o pical ster oi ds d uri n g st u d y partici pati o n s h o ul d be li mite d t o a v oi d  a n 
i m pact o n st u d y o utc o mes. I n case of t he i nte n de d use of t o pical oc ular ster oi ds, t he Me dical 
M o nit or s h o ul d be c o ns ulte d pri or t o t he start of t he me dicati o n, if p ossi ble.  
Ge nerall y, t he me dical m o nit or s h o ul d be c o ntacte d if t here are a n y q u esti o ns re gar di n g 
c o nc o mita nt or pri or t hera p y.  
7. 8. 1  Pr o hi bite d Me dic ati o ns a n d/ or Tre at me nts  
S u bjects s h o ul d n ot recei ve a n y me dicati o ns (a p pr o ve d or i n vesti gati o nal) f or t heir D M E i n 
t he st u d y e ye ot her t ha n t he st u d y dr u g as s pecifie d i n Ta ble 1 1  f or t he d urati o n of 
partici pati o n i n t he st u d y. T his i ncl u des  D M E  me dicati o ns a d mi nistere d l ocall y ( e. g., I V T, 
s u prac h or oi dal, t o pic al, j u xtascleral, or p eri or bital r o utes). 
Ta ble 1 1  lists treat me nts:  
•  t hat are c o nsi d ere d e xcl usi o nar y  a n d/ or pr o hi bite d de pe n de nt o n t he s u b gr o u p 
(treat me nt-n aï ve or pre vi o usl y treate d s u bjects)  
•  t hat q ualif y as f oll o w -o n treat me nt  per s u b gr o u p as descri be d i n Secti o n  7. 5. 2 , as well 
as all o we d treat me nt  f or t he st u d y e ye or fell o w e y e. 
F oll o w -o n treat me nt of t he st u d y e ye or ne wl y starte d treat me nt i n t he fell o w e ye wit h a p ort 
deli ver y s yste m is pr o hi bite d d uri n g partici pati o n i n t his trial d ue t o t he o verall a d de d 
c o m ple xit y i n t he s ur gical a d mi nistrati o n  pr oce d ure a n d p ost a d mi nistrati o n f oll o w -u p a n d  
care.

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Ta ble 11  Pr o hi bite d Me dic ati o ns a n d/ or Tre at me nts  
 
St u d y E ye Pre vi o usl y tre ate d 
St u d y E ye Tre at me nt -N ai ve  
Fell o w E ye  
T hera p y  
E xcl usi o n ar y  
i nter val bef ore 
scree ni n g 
Q ualifies as 
F oll o w -o n  
Treat me nt  
F or bi d de n  
i nter val bef ore 
scree ni n g 
Q ualifies as 
F oll o w -o n  
Treat me nt  
Part A 
F or bi d de n  
i nter val bef ore 
scree ni n g 
Part B  
F or bi d de n  
i nter val bef ore 
scree ni n g 
Ra ni biz u ma b or 
be vaciz u m a b (I V T)  
 4 wee ks  
Yes  
At a n y ti me  
Yes  
n o restricti o n,  
all o we d  
n o restricti o n,  
all o we d  
Afli berce pt  
 8 wee ks  
Yes  
At a n y ti me  
Yes  
n o restricti o n,  
all o we d  
n o restricti o n,  
all o we d  
Farici ma b or br ol uciz u m a b  
 1 2 wee ks  
Yes  
At a n y ti me  
Yes  
n o restricti o n,  
all o we d  
n o restricti o n,  
all o we d  
I V T P ort Deli ver y S yste m 
At a n y ti me  
N ot all o we d  
At a n y ti me  
N ot all o we d  
N ot all o we d  
N ot all o we d  
I ntra- or peri oc ular/s u bte n o n 
i njecti o n of tria mci n ol o ne 
acet o ni de  
At a n y ti me  
Yes  
At a n y ti me  
Yes  
 1 2 wee ks  
n o restricti o n,  
all o we d  
I V T de x a met has o ne i m pl a nt 
( Oz ur de x® )  
At a n y ti me  
Yes  
At a n y ti me  
Yes  
 2 4 wee ks  
n o restricti o n , 
all o we d  
I V T fl u oci n ol o ne i m pla nt 
At a n y ti me  
Yes  
At a n y ti me  
Yes  
At a n y ti me 
n o restricti o n,  
all o we d  

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St u d y E ye Pre vi o usl y tre ate d 
St u d y E ye Tre at me nt -N ai ve  
Fell o w E ye  
T hera p y  
E xcl usi o n ar y  
i nter val bef ore 
scree ni n g 
Q ualifies as 
F oll o w -o n  
Treat me nt  
F or bi d de n  
i nter val bef ore 
scree ni n g 
Q ualifies as 
F oll o w -o n  
Treat me nt  
Part A 
F or bi d de n  
i nter val bef ore 
scree ni n g 
Part B  
F or bi d de n  
i nter val bef ore 
scree ni n g 
S u prac h or oi dal Ster oi ds , 
e. g., Xi pere ™ 
At a n y ti me  
n ot all o we d  
At a n y ti me  
n ot all o we d  
 1 2 wee ks  
At a n y ti me  
Vitrect o m y  
 1 2 wee ks  
Yes  
 1 2 wee ks  
Yes  
n o restricti o n,  
all o we d  
n o restricti o n,  
all o we d  
F ocal ( Mac ular) Las er 
P h ot oc oa g ulati o n  
 1 6 wee ks  
Yes  
 1 6 wee ks  
Yes  
n o restricti o n,  
all o we d  
n o restricti o n,  
all o we d  
Pa nreti nal Laser 
P h ot oc oa g ulati o n ( P R P)  
 1 6 wee ks  
Yes  
 1 6 wee ks  
Yes  
n o restricti o n,  
all o we d  
n o restricti o n,  
all o we d  

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St u d y E ye Pre vi o usl y tre ate d 
St u d y E ye Tre at me nt -N ai ve  
Fell o w E ye  
T hera p y  
E xcl usi o n ar y  
i nter val bef ore 
scree ni n g 
Q ualifies as 
F oll o w -o n  
Treat me nt  
F or bi d de n  
i nter val bef ore 
scree ni n g 
Q ualifies as 
F oll o w -o n  
Treat me nt  
Part A 
F or bi d de n  
i nter val bef ore 
scree ni n g 
Part B  
F or bi d de n  
i nter val bef ore 
scree ni n g 
I n vesti gati o nal T hera pies f or 
M E (a ge nts wit h a nti -V E G F 
acti vit y, or c o m bi ne d 
p har mac ol o gic acti vit y, ge ne 
t hera pies, cell t hera pies, or 
a n y ot her t hera pe utic 
me dici nal pr o d uct)  
At a n y ti me  
N ot all o we d  
At a n y ti me  
N ot all o we d  
At a n y ti me  
At a n y ti me  
A nti -Gla uc o ma Dr u gs ( ma x 
of 2 acti ve c o m p o n e nts), if 
sta ble 
 
Yes  
 
 
n o restricti o n, 
all o we d  
n o restricti o n, 
all o we d  
Ocri plas mi n (Jetrea)  
At a n y ti me  
n.a.  
At a n y ti me  
n.a.  
n o restricti o n,  
all o we d  
n o restricti o n, 
all o we d  
Pri or s yste mic t hera p y wit h 
a nti-V E G Fs  
At a n y ti me  
n.a.  
At a n y ti me  
n.a.  
At a n y ti me  
At a n y ti me  
 

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7. 8. 2  C o nc o mit a nt Me dic ati o ns  
F or pre vi o us a n d c o n c o mita nt me dicati o ns, t he ori gi nal ter ms will be rec or de d o n t he St u d y 
S u bjects’ e C R F b y t he i n vesti gat or. Pre vi o us a n d c o nc o mita nt me dicati o ns will be c o de d  
acc or di n g t o W H O -D D  a n d ver bati m ori gi nal ter ms rec or de d o n t he e C R F will be prese nte d 
as data listi n gs.  
7. 9  
Criteri a f or Te m p or aril y Del a yi n g P art(s) of t he St u d y  
After t he re vie w of t he si x wee ks safet y data of 1 8 s u bjects fr o m Part A, a n d i n case of 
u nclear assess me nt of t he be nefit/ris k bala nce of t h e treat me nt wit h O X U -0 0 1, t he S p o ns or 
ma y deci de t o del a y t he i nitiati o n of Part B u ntil l o n ger -ter m d ata is a vailable f or re vi e w a n d 
assess me nt. T he decisi o n t o dela y, ter mi nate a n d re -i nitiate t he trial will be ma de b y t he 
s p o ns or after c o ns ultati o n wit h t he D M C. 
T he trial as a w h ol e or parts of t he st u d y ma y be d ela ye d i n case of t he d e v el o p me nt of e ve nts 
or sit uati o ns t hat ma y affect t he safet y of t he s u bjects, i n vesti gat ors, or staff me m bers a n d/ or 
i nte grit y of t he st u d y (e. g., e xtre me l oc k d o w n m eas ures ass ociat e d wit h C O VI D-1 9, nat ural 
disasters , a n d ot her force m aje ure e v e nts) . 
7. 9. 1  C O VI D -1 9 Rel at e d Prec a uti o ns  
A p pr o priate preca uti o ns t o li mit t he s prea d of C O VI D -1 9, i n acc or da nce wit h t he 
i n vesti gati o nal site’s sta n dar d pr oce d ures, s h o ul d be ta ke n.  
T he F D A g ui da nce o n t h e ma na ge m e nt of cli nical trials d uri n g t he C O VI D -1 9 pa n de mic 
( F D A G ui da nce o n C o n d uct of Cli nical Trials of Me dical Pr o d ucts D uri n g t he C O VI D-1 9 
P u blic Healt h E mer ge n c y, A u g ust 2 0 2 1) will be i m ple me nte d i n t his st u d y as a p plica ble. A 
m ore li mite d i m pact o n treat me nt is e x pect e d as t his cli nical trial will o nl y a d mi nister a si n gle 
treat me nt wit h st u d y me dicati o n a n d sta n dar d-of -care t hera p y t hereafter. T h e f oll o wi n g 
meas ures will be ta k e n:  
1.  
Assess me nt of t he feasi bilit y of starti n g t he cli nical trial at t he c h ose n sites i n cl ose 
c olla b orati o n wit h t he sites a n d fact ori n g i n p ote ntial ris k wit h re peat tra vel t o t he sites 
f or st u d y visits. 

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2.  
As t his cli nical trial was desi g ne d d uri n g t he o n g oi n g pa n de mic, n o desi g n c ha n ges 
relate d t o t he C O VI D-1 9 pa n de mic are e x p ecte d, b ut a peri o dic ris k assess m e nt ma y 
res ult i n a da ptati o ns necessitati n g a n a me n d me nt. 
3.  
If restricti o ns w o ul d n ot all o w t he tra vel of treate d s u bjects t o t he i n vesti gati o n site, 
safet y f oll o w-u ps c o ul d be perf or me d b y a l ocal o p ht hal m ol o gist.  
8  
Disc o nti n u ati o n of St u d y I nter ve nti o n a n d S u bject Dis p ositi o n Disc o nti n u ati o n/ 
Wit h dr a w al  
8. 1  
Disc o nti n u ati o n  of St u d y I nter ve nti o n  
S u bjects will recei ve a si n gle i nter ve nti o n at t he b aseli ne visit of t his trial. Disc o nti n uati o n of 
st u d y i nter ve nti o n is t heref ore n ot a p plica ble. See Secti o n 8. 2  bel o w f or dis c o nti n uati o n i n 
case of i n a bilit y t o a d mi nister t he st u d y me dicati o n.  
8. 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 s h o ul d re mai n i n t he st u d y u ntil t he fi nal visit ( Wee k 5 2); h o we v er, a s u bject’s 
partici pati o n i n t he st u d y ma y be disc o nti n ue d at a n y ti me. S h o ul d t his occ ur, t he reas o n f or 
disc o nti n uati o n m ust be d oc u me nte d i n t he wit h dra wal f or m.  Reas o ns f or disc o nti n uati o n 
i ncl u de t he i na bilit y t o a d mi nister trial me dicati o n wit h t he O x ul u mis®  de vice  des pite usa g e 
of all alter nati ve o pti o ns descri be d f or  V 2 acti vities . 
S u bjects w h o deci de t o disc o nti n ue st u d y partici pati o n f or a n y reas o n  will u n der g o all e n d of 
st u d y visit assess me nts a n d pr oce d ures a n d t he visit will be c o nsi dere d a n e n d of st u d y visit.  If 
f or a n y reas o n t he st u d y treat me nt c a n n ot be a d mi nistere d, a n e xtr a e n d of st u d y visit is n ot 
necessar y a n d o nl y a cti vities f or Visit 2 nee d t o be c o m plete d as a p plica ble.  
S u bjects m ust be i nf or me d a b o ut t heir ri g ht t o wit h dra w fr o m t he st u d y at a n y ti me a n d f or 
a n y reas o n wit h o ut sa ncti o n, pe nalt y, or l oss of be nefits t o w hic h t he s u bject is ot her wise 
e ntitle d. Wit h dra wal fr o m t he st u d y will n ot je o par dize t he s u bj ect’s f ut ure me dical care or 
relati o ns hi p wit h t he i n vesti gat or.  
S u bjects will be as ke d t o s pecif y t he reas o n f or t he ter mi nati o n b ut ha ve t he ri g ht n ot t o 
a ns wer. I n t his cas e, o nl y p ote ntiall y o n g oi n g a d verse e ve nts or a d verse de vice effects  will be 
f oll o we d-u p, if t he s u bject a grees.  

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T he i n vesti gat or ma y deci de t o wit h dra w a s u bject fr o m t he st u d y at a n y ti me wit h reas o na bl e 
rati o nale. 
T he s u bject’s f ut ure care will n ot be i nfl ue nce d b y a decisi o n, v ol u ntar y or ot her wise, t o 
wit h dra w fr o m t he st u d y. All reas o n a ble eff orts s h o ul d be ma de t o retai n t h e s u bject i n t he 
cli nical st u d y u ntil t he c o m pleti o n of t he st u d y.  
Reas o ns f or a s u bject’s wit h dra wal i ncl u de, b ut are n ot li mite d t o:  
1.  
S u bject ref uses t o c o nti n ue partici pati n g i n t he st u d y  
2.  
S u bject’s n o n -c o m plia nce  
3.  
S u bject’s partici pati o n is ter mi nate d b y t he PI or i n vesti gat or, alt h o u g h t he s u bject 
c o nse nte d si nce p artici pati o n is n o l o n ger me dicall y a p pr o priate  
4.  
S u bject is ‘l ost t o f oll o w u p’: if t he s u bject re p eate dl y fails t o ret ur n f or sc h e d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he st u d y sit e (see Secti o n 8. 3 ). 
N ote: If a s u bject misses o ne or m ore of t he sc he d ule d f oll o w -u p visits (i ncl usi ve of t he 
assi g ne d visit wi n d o ws), t his will be c o nsi dere d a misse d visit. T he s u bject ma y t heref ore still 
ret ur n f or s u bs e q ue nt visits a n d will n ot be e xcl u de d fr o m t he st u d y. 
If a s u bject wit h dra ws fr o m t he cli nical st u d y, t he site will rec or d t he s u bject’s reas o ns f or 
wit h dra wal o n a Wit h dra wal C R F. W he n t he s u bject’s wit h dra wal fr o m t he st u d y is d ue t o a n 
a d verse e ve nt t he s u bject will be f oll o we d u ntil t he res ol uti o n of t hat  a d verse e ve nt or 
deter mi nati o n t hat t he s u bject’s c o n diti o n is sta ble f or a ma xi m u m d urati o n of si x ( 6) m o nt hs. 
T he stat us of t he s u bject’s c o n diti o n s h o ul d be d oc u me nte d at t he ti me of wit h dra wal.  
8. 3  
L ost t o F oll o w -U p  
A s u bject will be c o nsi dere d l ost t o f oll o w -u p if t he s u bject re p eate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site. 
T he f oll o wi n g acti o ns m ust be ta ke n if a s u bject f ails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit: 
1.  
T he site m ust 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 as s o o n as 
p ossi ble, 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 ne d visit 
sc he d ule a n d ascertai n w het her 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 ud y.  

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2.  
Bef ore a s u bj ect 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 ne e m ust ma ke 
e ver y eff ort t o r e gai n c o ntact wit h t he s u bject ( w h ere p ossi ble, 2 tele p h o ne calls, a n d if 
necessar y, a certifie d lett er t o t he s u bject’s last k n o w n maili n g a d dress or l oc al 
e q ui vale nt met h o ds). T hese c o ntact 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.  
3.  
S h o ul d t he s u bject c o nti n ue t o be u nreac ha bl e, t he s u bject will be c o nsi dere d l ost t o 
f oll o w-u p.  
9  
St u d y Assess me nts a n d Pr oce d ures  
St u d y pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o As i n Secti o n 1. 3 . Pr ot oc ol 
wai vers or e xe m pti o ns are n ot all o we d.  
If n ot s pecificall y i n dicate d, descri pti o ns a p pl y f or Part s A a n d B of t his cli nical trial.  
A d here n ce t o t he st u d y d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o As, is 
esse ntial a n d re q uire d f or t he trial c o n d uct.  
All scree ni n g e v al uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial s u bjects 
meet all eli gi bilit y criteria.  Scree ni n g assess me nts ca n be p erf or m e d o n differe nt da ys wit hi n a 
scree ni n g p eri o d of u p t o 3 0 da ys, if o perati o nall y re q uire d. O nl y f or t he visit wi n d o w of t he 
Scree ni n g Visit , a n e xt e nsi o n of t he visit wi n d o w t o 3 7 da ys ca n b e a p pr o ve d b y t he O x ular 
Me dical M o nit or base d o n a n i n di vi d ual re q uest of t he i n vesti gat or stati n g i m p orta nt me dical 
a n d/ or or ga ni zati o nal reas o ns. Als o, selecte d assess me nts li ke bl o o d press ure meas ure me nts 
ma y be re p eate d o n a differe nt visit da y after t he i nitial scree ni n g , t o meet eli gi bilit y criteria. 
S uc h re peat assess me nts nee d t o be me dicall y pla usi ble, e. g., if a s u bject h as f or g otte n t o ta ke 
a nti h y perte nsi ve me dic ati o n o n t he da y of t he i nitial sc ree ni n g visit, or if t he B C V A 
assess me nt s h o ws val ues j ust o utsi de t he eli gi bilit y c orri d or a n d a sli g ht f urt her decrease i n 
B C V A d uri n g t he scree ni n g peri o d w o ul d be e x p ecte d.  If d u plicate assess m e nts are re q uire d, 
e. g., f or B C V A, t hese d u plicates ha ve t o be perf or me d o n t he sa me scree ni n g visit da y, or i n 
case t he y w o ul d n ee d t o be re peate d, als o t he re peat meas ure m e nt w o ul d ha ve t o be 
perf or me d i n d u plic ate.  T he i n vesti gat or will mai ntai n a scree ni n g l o g t o rec or d details of all 
s u bjects scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or scree ni n g fail ure, as 
a p plica ble.  
Pr oce d ures c o n d ucte d as part of t he s u bject’s r o uti ne cli nical ma na g e me nt ( e. g., S D -O C T 
i ma gi n g, I O P meas ure m e nt, etc.) a n d o btai ne d b ef ore si g ni n g of t he I C F ma y be utilize d f or 

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scree ni n g or b aseli ne p ur p oses pr o vi de d t he pr o ce d ures met t he pr ot oc ol -s p ecifie d criteria a n d 
were p erf or me d wit hi n t he ti mefra me d efi ne d i n t h e S o As.  
T he f oll o wi n g ge neral rec o m me n dati o ns a p pl y f or t he se q ue nce of st u d y assess me nts:  
•  T he N EI V F Q -2 5 i nstr u me nt is rec o m me n de d t o be assesse d first o n a visit da y t o a v oi d 
bias b y o utc o mes of st u d y assess me nts  (see als o Secti o n 9. 2. 1 0 ). 
•  As s o me of t he assess me nts, s pecificall y i ma gi n g assess me nts are p erf or me d after dilati o n 
of t he p u pil(s), assess me nt ca n be gr o u p e d i n pre -dilati o n a n d p ost -dilati o n assess me nts.  
o  T he f oll o wi n g assess me nts are rec o m me n de d t o b e perf or me d bef ore dilati o n:  
▪ Vital si g ns, pre g na nc y test, B C V A, I O P, slit -la m p bi o micr osc o p y, a n d 
a nteri or se g me nt O C T.  
o  T he f oll o wi n g assess me nts are rec o m me n de d t o b e perf or me d after dilati o n:  
▪ A xial le n gt h, S D -O C T  i ncl u di n g 4 Wi de -Fi el d I R Pl us i ma gi n g, peri p heral 
O C T, c ol or f u n d us p h ot o, safet y, a n d P K la b ( P K o nl y i n Part A), 
fl u orescei n a n gi o gra p h y, a n d dilate d o p ht hal m osc o p y.  
▪ Ve ni p u nct ure f or la b ass ess me nts a n d pre -d osi n g P K ( Part A, Visit 2 , 
Da y  0 ) ma y b e perf or me d after dilati o n s o t hat  t he bl o o d sa m ple c ollecti o n 
ca n be c o m bi ne d  wit h  t he ve ni p u nct ure n ee d e d f or t he  fl u ores cei n 
a n gi o gra p h y.  
I n t he e ve nt of a si g nifica nt st u d y-c o nti n uit y iss ue ( e. g., ca us e d b y a p a n de mic), alter nate 
strate gies f or s u bject visits, assess me nts, me dicati o n distri b uti o n, a n d m o nit ori n g ma y be 
i m ple me nte d b y t he s p o ns or or t he i n vesti gat or, as per l ocal healt h a ut h orit y/et hics 
re q uire me nts.  
Access t o safet y, i ma gi n g, or ot her data t h at c o ul d p ote ntiall y u n mas k t he st u d y will be 
li mite d t o u n mas ke d i n di vi d uals as s pecifie d i n Secti o n 7. 3 . 
9. 1  
E v al u ati o ns Perf or me d D uri n g I n vesti g ati o n al Visits  
E val uati o ns will be perf or me d at s pecifi c visits as s h o w n i n t he S o As i n Secti o n 1. 3 . 
9. 1. 1  B aseli ne Visit V 2  Acti vities  
Acti vities of t he baseli ne visit nee d t o be a da pte d b ase d o n t he setti n g f or t h e a d mi nistrati o n 
of st u d y treat me nt (i n -cli nic/ pr oce d ure r o o m or s ur gicall y e q ui p pe d pr oce d ure r o o m/ o perati n g 
r o o m, Alter nati ve Sc h e d ule N o. 1 a n d N o. 2), a n d t he nee d t o s witc h t he setti n g i n case of n o n -

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c o m pleti o n of a d mi nistrati o n of st u d y treat me nt i n -cli nic/ pr oce d ure r o o m  ( Alter nati ve 
Sc he d ule N o. 3) . T h e t hree alter nati ves f ores ee n i n t his trial are s u m marize d i n Ta ble 3  f or Part 
A a n d i n Ta ble 4  f or Part B. As s ur gical ce nters ma y be i n differe nt facilities  fr o m 
i n vesti gati o nal sites, n ot all sta n dar d assess me nts f or V 2 ma y b e p ossi ble. T heref ore, s pecific 
a da ptati o ns f or V 2 i n Alt er nati ve N o. 2 a n d N o. 3 are ma de.  
T he decisi o n a n d pla n ni n g f or t he se q u e nce of V 2 acti vities a n d t he c h oice of t he alter nati ve 
sc he d ule N o. 1-N o. 3 will be base d o n a n e x pert ass ess me nt of t he e x pecte d c o m ple xit y of t he 
O X U -0 0 1 pr o ce d ure f oll o wi n g t he g ui da nce i n Secti o n 1 2. 4 . 
F or Part B, t he setti n g  f or st u d y treat me nts is deter mi ne d bef ore t h e ra n d o mizati o n t o I V T 
Oz ur de x ®  or o ne of t w o s u prac h or oi d al O X U -0 0 1  treat me nt ar ms a n d will f or mas ki n g 
p ur p oses als o n ot be c h a n ge d, if t he u n mas ke d tea m lear ns a b o ut a mas ke d Oz ur de x ®  
treat me nt sc he d ul e d f or a n o perati n g/s ur gicall y e q ui p pe d pr oce d ure r o o m.  
T he date f or cal c ulati o n of visits f oll o wi n g Visit 2, Da y 0 will be t he date of c o m pleti o n of 
a d mi nistrati o n of st u d y treat me nt, i.e., it ca n be t h e date of t he 2 n d s essi o n f or treat me nt 
a d mi nistrati o n . 
9. 1. 2  O pti o n al S afet y Visit Wee k 6 –  P art B  
At t he discreti o n of t he i n vesti gat or, a n a d diti o nal visit ca n be sc he d ule d f or s u bjects 
partici pati n g i n Part B at Wee k 6 +/ - 5 da ys. T his visit is rec o m me n de d if s u bjects s h o w i n t he 
o pi ni o n of t he i n vesti gat or  a tre n d f or a n I O P i ncrease i n t he pri or visits 3 –  5. T he o pti o nal 
safet y visit has a n a b bre viate d sc he d ule of assess me nts c o m pare d t o ot her re g ular visits as 
pr o vi de d i n Secti o n 1. 3 . 
9. 1. 3  E arl y Ter mi n ati o n Visit  
A n earl y ter mi nati o n  ( E T) visit s hall be perf or me d if s u bjects deci de t o st o p t heir partici pati o n 
i n t he st u d y. S u bjects are free t o wit h dra w c o ns e nt at a n y ti me d uri n g t he st u d y wit h o ut 
prej u dice. A n y s u bject w h o wit h dra ws c o nse nt s h o ul d be as ke d a b o ut t he reas o n(s) a n d t he 
prese nce of a n y A Es at t he ti me of wit h dra w n c o nse nt. T he act ual visit sc he d ule will be 
e xten de d b y t he assess me nts f oresee n f or t h e e n d of st u d y ( E o S) visit as lai d o ut i n Ta ble 1  
( Part A) a n d Ta ble 2  ( Part B). F or s u bjects i n w h o m t he st u d y treat me nt c o ul d n ot be 
a d mi nistere d, a n e xtr a E O S/ E T visit is n ot perf or me d.  

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9. 1. 4  U nsc he d ule d Visit  
All atte m pts s h o ul d be ma de t o kee p s u bjects o n t he st u d y sc he d ule. H o we ver, u nsc he d ul e d 
visits ma y be necessar y if a b n or mal fi n di n gs or A Es occ ur t o e v al uate f urt her or re peat testi n g 
f oll o wi n g a b n or mal fi n di n gs, or f or a n y ot her reas o n, as warra nte d. 
9. 2  
A d mi nistr ati ve a n d Ge ner al/ B aseli ne Pr oce d ures  
9. 2. 1  C o nse nt F or m C o m pleti o n  
F oll o wi n g I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee (I R B/ E C) a p pr o val a n d bef ore a n y 
i n vesti gati o n-relate d pr oce d ure, p ot e ntial s u bjects will be as ke d t o si g n a writte n i nf or me d 
c o nse nt f or m (I C Fs). T he s u bjects will be gi ve n s ufficie nt ti me f or t he i nf or mati o n t o be rea d 
a n d u n derst o o d. T he s u bj ect will be a p pr oac he d a n d gi ve n t he c ha n ce t o as k a n y q uesti o ns 
t hat ha ve aris e n after rea di n g t he I C Fs. F or m ore i nf or mati o n o n t he i nf or m e d c o nse nt, 
pr ocess se e Secti o n 1 1. 1. 3 . 
9. 2. 2  De m o gr a p hic I nf or m ati o n a n d Me dic al Hist or y  
At t he scree ni n g visit, i nf or mati o n a b o ut t he s u bject’s de m o gra p hics, a n d m e dical/s ur gical 
hist or y, will be o btai ne d.  
De m o gra p hics v aria bles  t o be c ollecte d are: age, g e n der, race, a n d et h nicit y (i n acc or da nce  
wit h  t he U S F D A g ui da nce d oc u me nt (U S F D A 2 0 1 6 ).  
9. 2. 3  Eli gi bilit y Assess me nt  
At t he Scree ni n g visit, t he p ote ntial s u bjects’ eli gi bilit y will be assesse d base d o n meeti n g all 
t he i ncl usi o n a n d n o ne of t he e xcl usi o n criteri a. O n, or pri or t o t he baseli ne visit ( Visit 2 , 
Da y  0 ), an a d diti o nal  eli gi bilit y re vie w is perf or me d  u p o n re vie w of t h e la b orat or y res ults, 
uri ne pre g n a nc y test ( U P T ), a n d res ults of t he C R C assess me nt of C S T per i ncl usi o n criteri o n, 
a n d a n y c h a n ge i n c o n c o mita nt me dicati o n or me dical hist or y si nce t he scree ni n g visit, t hat 
ma y re n der a s u bject  i neli gi ble f or partici pati o n. B C V A will be assess e d at t he baseli ne visit 
als o, b ut f or t he eli gi bilit y deter mi nati o n  o nl y  t he assess me nt fr o m t he scree ni n g visit is 
rele va nt. 
 
 

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9. 2. 4  Assess me nt of E x pecte d Pr oce d ur al C o m ple xit y  
T he treati n g p h ysicia n (w h o is a n u n mas ke d i n vesti gat or i n Part B)  will assess at t he scree ni n g 
visit t he e x pecte d pr o ce d ural c o m ple xit y i n cate g ories of l o w, me di u m, or hi g h . F or t he 
g ui da nce d oc u m e nt see S ecti o n 1 2. 4 . If s u bject c h aract eristics (e. g., e n o p ht hal m os, a n d/ or 
t hic k, o pa q ue c o nj u ncti v a or si milar feat ures) s u g gest a n i ncrease d c o m ple xit y f or e n ga gi n g 
t he O x ul u mis®  i nserti o n nee dle i nt o t he sclera, t he O X U-0 0 1 C o njI ncisi o n  Pr oce d ural V aria nt 
wit h a n i ncisi o n of t he c o nj u ncti va/te n o n  ma y be use d . T his pr oce d ural varia nt is e x pecte d t o 
be carrie d o ut aft er l ocal i njecti o n a nest hesia i n a n o perati n g  or s ur gi call y e q ui p pe d  pr oce d ure 
r o o m. L ocall y esta blis he d pr oce d ural practices f or c o nj u ncti val/te n o n i ncisi o n a n d cl os ure 
will be use d at t he discreti o n of t he treati n g p h ysicia n. Als o i n Part B, t he pr oce d ural s etti n g 
f or t he Baseli ne Visit V 2 is alrea d y pla n ne d as part of t he Scree ni n g Visit acti vities. F or 
mas ki n g p ur p oses,  t he i n vesti gat or decisi o n o n e. g ., perf or mi n g t he st u d y tr eat me nt directl y i n 
a n o perati n g/r o o m  will n ot be re verse d i n s u bjects ra n d o mize d t o r ecei ve I V T Oz ur de x ® . 
9. 2. 5  Pre g n a nc y Test  
F or w o me n of c hil d beari n g p ote ntial, a ne gati ve s er u m pre g n a nc y test at scree ni n g (Visit 1 , 
Da y -3 0 t o Da y -2 ) a n d uri ne pre g n a nc y test at bas eli ne (Visit 2 , Da y 0) is r e q uire d f or 
eli gi bilit y. A d diti o nal uri ne pre g na n c y tests will be perf or me d o n Visit s 4-1 8 ( Wee k  5 2) . F or 
t he pre g n a n c y test o n Visit  3, Da y 1, t he i nter val si nce pri or test o n D a y 0 is c o nsi dere d t o o 
s h ort. 
9. 2. 6  A d verse E ve nt a n d A d v erse De vice Effect C ollecti o n  
At e ver y visit, t he i n vesti gat or ( or desi g n ee) will assess f or a n d rec or d all A Es a n d A D Es t h at 
occ ur fr o m t he ti me t he i nf or me d c o ns e nt is si g ne d u ntil t he e n d of st u d y. M ore details are 
wit hi n Secti o n  9. 4. 1 . 
9. 2. 7  C o nc o mit a nt Me dic ati o n Re vie w  
A n y me dicati o n or vacci ne (i ncl u di n g o ver -t h e-c o u nter or pres cri pti o n me dici nes, vita mi ns, 
a n d/ or her bal s u p ple me nts) t hat t he s u bject recei ves at t he ti me of e nr ol me nt or recei ves 
d uri n g t he st u d y m ust be rec or de d at e ac h visit al o n g wit h:  
1.  
Reas o n f or use  
2.  
Dates of a d mi nistrati o n i ncl u di n g start a n d st o p dates  
3.  
Start a n d st o p dates f or c ha n ges i n me dicati o ns a n d c ha n ges i n d ose  

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4.  
D osa ge i nf or m ati o n i ncl u di n g t he r o ute of a d mi nistrati o n, d ose, a n d fre q ue n c y  
T he me dical m o nit or s h o ul d be c o ntacte d if t h ere are a n y q u esti o ns re gar di n g c o nc o mita nt or 
pri or t hera p y.  
9. 2. 8  P h ar m ac o ki netic Bl o o d S a m pli n g  
I n Part A, wh ol e bl o o d sa m ples of a p pr o xi matel y [ 5] m L will be c ollecte d f or meas ure m e nt of 
plas ma c o nce ntrati o ns of st u d y i nter ve nti o n o n Visits 1, 2, 3, 4, 5, 1 1, a n d 1 8 (scree ni n g, Da ys 
0 [ 6 0 mi n  after a d mi nistrati o n of t he st u d y treat me nt], a n d Da y 1, wee k 1, 4, 2 4, a n d 5 2, 
res pecti vel y) as s pecifie d i n t he S o A of Part A (Ta ble 1 ). F urt her details are a vaila ble i n  
Secti o n 9. 6 .  
9. 2. 9  St u d y I nter ve nti o n  
Details o n st u d y i nter ve nti o ns ca n be f o u n d i n  Secti o n 6 . 
9. 2. 1 0  N EI V F Q -2 5  
Nati o nal E ye I nstit ute 2 5 -ite m vis ual f u ncti o n q uesti o n naire ( N EI V F Q-2 5) is a c o m m o nl y 
use d i nstr u me nt t o deter mi ne t he visi o n -relate d q ualit y of life. T he N EI-V F Q 2 5 will be 
assesse d at scree ni n g, 2 4, a n d wee k 5 2 visits ( Visits 1, 1 1, a n d 1 8, res p ecti v el y ), as s pecifie d 
i n t he S o As (Ta ble 1  - Part A a n d Ta bl e 2  - Part B ). 
T he N EI V F Q -2 5 will be prese nte d i n t he l ocal la n g ua ge a n d a d mi nistere d i n a q uiet setti n g, 
prefera bl y bef ore ot her st u d y pr oce d ures are perf or me d  b y mas ke d site staff i n Part B . 
De pe n di n g o n t he s u bject’s vis ual ac uit y a n d rea di n g a bilit y, eit her t he i nter vie wer or t h e self -
a d mi nistere d N EI V F Q -2 5 versi o n will be use d. F or t he self -a d mi nistere d versi o n, t he 
s u bjects will c o m plete t he self-a d mi nistere d N EI V F Q 2 5. F or t he i nter vie wer versi o n, trai ne d 
site staff s h o ul d perf or m t he i nter vie w a d mi nistere d N EI V F Q -2 5 wit h t he s u bject. T he 
met h o d of a d mi nisteri n g t he q uesti o n naire s h o ul d re mai n t he sa me t hr o u g h o ut t he st u d y. If a 
s u bject’s visi o n deteri orates s o t hat t he y are n ot a ble t o self-a d mi nister t he q uesti o n naire at 
a n y ti me after t he s cree ni n g visit, a n i nter vie w a d mi nistere d q uesti o n naire will be perf or me d 
i nstea d. M ore details are pr o vi de d i n t he N EI V F Q-2 5 ma n ual.  
9. 2. 1 1  D oc u me nt ati o n a n d Assess me nt of t he A d mi nist r ati o n Pr oce d ure  
S h ortl y after t he pr oce d ure a d mi nistrati o n  o n treat me nt da ys of t he baseli ne visit V 2  a n d 
re gar dl ess of c o m pleti o n of st u d y treat me nt, t he treati n g p h ysicia n  (u n mas k e d i n vesti gat or i n 

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Part B) will d oc u me nt t he pr oce d ure d etails a n d  c o m plete t he pr oce d ure assess me nt q uesti o ns 
(f or details see Secti o n 1 2 . 3).  
If t he O x ul u mis®  pr oce d ure is re peate d, i.e., if t h e O X U-0 0 1 a d mi nistrati o n pr oce d ure is 
perf or me d  o n t w o treat m e nt da ys or i n 2 se parate sessi o ns o n o ne da y, t he q uesti o n naire will 
nee d t o be c o m plet e d t wice. If t h e varia nt w o ul d b e s witc he d wit hi n o ne treat me nt sessi o n 
(e. g., i n a n o perati n g r o o m wit h a first n o n-c o m plete d O X U -0 0 1 Sta n dar d  pr oce d ural varia nt 
directl y f oll o we d b y a n O X U -0 0 1 C o njI ncisi o n  Pr oce d ural Varia nt , o nl y o ne assess me nt 
nee ds t o be c o m plete d.  
9. 2. 1 2  P atie nt E x perie nce Assess me nt  
Details a b o ut t he s u bject's e x perie n ce d uri n g a n d after t he pr oce d ure will be c ollecte d ( b y 
mas ke d site staff i n Part B). F or details see Secti o ns 1 2. 1  a n d Secti o n 1 2. 2 . It is ma n dat ory  t o 
gi ve i nstr ucti o ns t o t he s u bject at t he be gi n ni n g of t he i nter vie w t o o nl y a ns wer t he i nter vi e w 
q uesti o ns . T his is s pecificall y i n part B i nte n de d t o a v oi d s hari n g of p ote ntiall y u n mas ki n g 
i nf or mati o n a b o ut t he pr oce d ure.  
T he Patie nt E x perie n ce asse ss me nt will o nl y be c o m plete d after c o m pleti o n of a d mi nistrati o n 
of st u d y treat me n t. S pecificall y, i n V 2 acti vit y alter nati ve N o. 3 (s ee Ta ble 3  a n d Ta ble 4 ), t he 
assess me nt will o nl y be perf or me d  after c o m pleti o n of treat me nt  o n t he 2 n d treat me nt da y of 
V 2 . 
9. 2. 1 3  Dis p ositi o n of S a m ples  
A n y re mai ni n g bl o o d, plas ma, ser u m, or uri ne sa m ples c ollecte d f or l a b orat or y testi n g will be 
destr o ye d.  
9. 3  
Oc ul ar Assess me nts  
Pla n ne d ti me p oi nts f or all oc ular assess me nts are pr o vi de d i n t he S o As i n Secti o n 1. 3 . 
9. 3. 1  A xi al Le n gt h Me as ure me nt  
A xial le n gt h meas ure m e nt will assess  t he a xial di me nsi o ns of t he e ye t o s u p p ort e x pl orat or y 
i ma gi n g of t he l ocati o n of t he de pl o y me nt of st u d y dr u g i n e q ui p pe d sites o nl y. A xial le n gt h 
will be meas ure d  at e q ui p pe d sites  at t he scree ni n g visit i n b ot h e yes usi n g a n o n -c o ntact 
o ptical bi o metr y de vice ( e. g., partial c o here n ce i nt erfer o metr y ( P CI) usi n g t he I O L M aster 

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( Carl Zeiss Me ditec A G), Le ns Star ( Haa g-Streit, S witzerla n d), Pe nt aca m A X L ( Oc ul us 
O pti k geräte G m b H, Ger ma n y)).  
If sites are n ot e q ui p pe d t o meas ure a xial le n gt h wit h o ne of t he i n dicate d de vices, t he a xi al 
le n gt h c o ul d be retri e ve d fr o m me dical r e p orts, e. g., i n s u bjects w h o have  u n der g o ne le ns 
re place me nt s ur ger y i n t he past. F or s uc h val ues ta ke n fr o m me dical hist or y, t he date (at least 
t he year) of t he meas ure me nt has t o be rec or de d.  
9. 3. 2  I O P Me as ure me nt 
I O P of t he st u d y e ye will be assesse d at e ver y visit usi n g G ol d ma n n a p pla nati o n t o n o metr y or 
t he To n o -pe n ™, as s pecifie d i n t he S o As i n S ecti o n 1. 3 . T he sa me met h o d of I O P 
meas ure me nt  use d at scree ni n g  m ust be use d t hr o u g h o ut t he st u d y f or a n i n di vi d ual s u bject.  
I O P meas ure me nt i n t he fell o w e ye will be assess e d at t he scree ni n g, bas eli ne, Wee k 1 2, 
Wee k  2 4, a n d Wee k 5 2 visits, as s pecifie d i n t he S o As i n Secti o n 1. 3 .  
After c o m plet e or partial treat me nt a d mi nistrati o n  at t he baseli ne visit, I O P meas ure me nt i n 
t he st u d y e ye m ust be p er f or me d at least t wice o ver  t he 6 0 mi n utes f oll o wi n g treat me nt u ntil 
n or malizati o n.  S u bjects will o nl y be disc har ge d  if t he I O P is n or mal after t hat f oll o w-u p 
peri o d or if I O P l o w eri n g meas ures ha v e bee n ta ke n. N o I O P m o nit ori n g is necessar y, neit her 
a c o m plete n or a partial O X U -0 0 1 d ose h as bee n a d mi nistere d.  F or s pecifi c g ui da nce o n 
sc he d uli n g of I O P me as ure me nts i n t he o perati o nal alter nat i ves N o. 1-N o. 3 see Ta bl e 3  f or 
Part A, a n d Ta ble 4  f or Part B. 
9. 3. 3  Slit -L a m p Bi o micr osc o p y  
S u bjects’ a nteri or oc ular str uct ure  (i ncl u di n g ass ess me nt a n d s yste matic gra di n g of le ns 
o pacities ) a n d o c ular a d n e xa will be e x a mi ne d i n t he st u d y e ye at eac h st u d y visit usi n g a slit 
la m p, as s pecifie d i n t he S o A’s i n Secti o n 1. 3 . T he s yste matic slit la m p e xa mi nati o n will 
c o m prise oc ular a d ne x a, oc ular s urface, a q ue o us h u m or a n d vitre o us, iris a n d p u pil, a n d t he 
le ns. Le ns o pacit y assess me nts will be gra de d f oll o wi n g t he scale s u g geste d b y t he W H O 
Cataract gr a di n g gr o u p  (T h ylef ors et al., 2 0 0 2 ; T he W H O C ataract Gra di n g Gr o u p 2 0 0 2 ). 
Gra di n g will c o m prise t h e s u bcate g ories n uclear cataract, c ortical cataract, a n d p osteri or 
s u bca ps ular cataract. Gra di n gs  ra n ge fr o m gra de 0 t o gra de 9 f or eac h of t h e cate g ories. 
Gra de  9 me a ns ca n n ot gr a de. Sites ma y use a s o urce data s h eet t o s u p p ort t he le ns o pacit y 
gra di n g.  

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Slit -la m p bi o micr osc o p y i n t he fell o w e ye will be assesse d at t he s cree ni n g, baseli ne, 
Wee k  1 2, Wee k 2 4, a n d Wee k 5 2 visits, as s pecifi e d i n t he S o As i n Secti o n 1. 3 . 
F or s pecific g ui da nce o n sc he d uli n g of slit -la m p bi o micr osc o p y i n t he o perati o nal alter nati ves 
N o. 1 -N o. 3 see Ta ble 3  f or Part A, a n d Ta ble 4  f or Part B. 
9. 3. 4  Dil ate d I n direct O p ht h al m osc o p y  
S u bjects’ p osteri or p ole a n d peri p heral reti na will be e xa mi ne d b y dilate d i n direct 
o p ht hal m osc o p y at eac h st u d y visit i n t he st u d y e ye, as s pecifi e d i n Secti o n 1. 3 . A p ost-d ose 
e val uati o n m ust be perf or me d after i njecti o n.  
F or s pecific g ui da nce o n sc he d uli n g of dilate d i n direct o p ht hal m osc o p y i n t he o perati o nal 
alter nati ves N o. 1 -N o. 3 see Ta ble 3  f or Part A, a n d Ta ble 4  f or Part B.  
Dilate d i n direct o p ht hal m osc o p y i n t he fell o w e y e will be perf or me d at t h e scree ni n g, 
baseli ne, Wee k 1 2, Wee k 2 4 , a n d Wee k 5 2  visits, as s pecifie d i n t he S o As i n Secti o n 1. 3 . 
9. 3. 5  Best -C orrecte d Vis u al Ac uit y  
Ma nifest refracti o n will be c o n d ucte d pri or t o t he B C V A assess me nt.  
T he B C V A assess me nt will be c o n d ucte d pri or t o dilati n g p u pils, usi n g t he sta n dar d E T D R S 
pr ot oc ol at 4 meters wit h bac k -ill u mi nate d e ye c h arts a n d bef ore a n y ot her oc ular 
pr oce d ures/assess me nts r e q uiri n g c o ntact wit h t he e ye are perf or me d.  
B C V A i n t he st u d y e ye will be assesse d at all visits  b y mas ke d site staff i n Part B , as s pecifie d 
i n t he S o As i n Secti o n 1. 3 . F or s pecific g ui da nce o n sc he d uli n g of B C V A  assess me nts  i n t he 
o perati o nal alter n ati ves N o. 1 -N o. 3 see Ta ble 3  f or Part A, a n d Ta ble 4  f or Part B. 
All B C V A assess me nts i n t he st u d y e ye nee d t o b e perf or me d i n d u plicate. B ot h 
meas ure me nts will be e nt ere d i n t he C R F. F or eli gi bilit y deter mi nati o n at t he scree ni n g visit, 
t he mea n of b ot h B C V A assess me nts will be calc ulate d, if b ot h E T D R S letters sc ores d o n ot 
differ b y m ore t ha n 5 lett ers. If t he differe nce is gr eater  t ha n 5 l etters, t he better ( hi g her) 
E T D R S letter sc ore will be use d. F urt her details o n ha n dli n g d u plicate B C V A assess me nts 
will be descri be d i n t he S A P.  
Refracti o n o nl y ne e ds t o be perf or me d a si n gle ti me, if d u plicate B C V A assess me nts are 
perf or me d s e q ue ntiall y.  

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B C V A i n t he fell o w e ye will be assesse d at t he scree ni n g, bas eli ne, Wee k 1 2, Wee k 2 4 , a n d 
Wee k 5 2  visits, as s pecifi e d i n t he S o As i n Secti o n 1. 3 . F or B C V A assess me nts i n t he fell o w 
e ye, o nl y si n gle meas ur e me nts are nee de d.  B C V A assess me nt will be perf or me d b y a certifie d 
vis ual ac uit y e xa mi ner , w h o is mas ke d t o t he st u d y treat me nt i n Part B. 
9. 3. 6  S pectr al -D o m ai n O ptic al C o here nce To m o gr a p h y  
Reti nal str uct ure a n d p at h ol o gical c ha n ges will be e val uate d at e ver y visit usi n g S D -O C T. 
S D -O C T i ma ges will be ca pt ure d a n d tra ns mitte d t o t he C R C  via a n e ncr y pte d sec ure we bsite. 
All S D O C Ts will be electr o nicall y arc hi ve d at t h e i n vesti gati o nal sites as part of t he s o urce 
d oc u me ntati o n.  
Acce pt a ble O C T ma c hi nes are S pectralis ( Hei del ber g E n gi neeri n g G m b H) a n d Cirr us ( Carl 
Zeiss Me ditec A G). Ot her de vices n ee d t o be a p pr o ve d b y t he s p o ns or u p o n re q uest. T he s a me 
de vice s h o ul d be use d f or scree ni n g , b aseli ne,  a n d t he s u bse q ue nt f oll o w -u p assess me nts f or 
eac h s u bject. 
S D -O C T will be perf or me d at eac h visit f or t he st u d y e ye.  
F or s pecific g ui da nce o n sc he d uli n g of S D -O C T  assess me nts  i n t he o perati o nal alter nati ves 
N o. 1 -N o. 3 see Ta ble 3  f or Part A, a n d Ta ble 4  f or Part B. 
F or t he  fell o w e ye, S D -O C T will be perf or me d at t he scree ni n g, baseli ne, Wee k 1 2, Wee k 2 4, 
a n d Wee k 5 2 visits, as s pecifie d i n t he S o As i n Secti o n 1. 3 . F urt her details are i ncl u de d i n t he 
i ma gi n g ma n ual i ncl u di n g details o n  4 -Wi de -Fiel d Near i nfrare d (I R) Pl us i ma gi n g at sites 
e q ui p pe d wit h a Hei d el ber g S pectr alis de vice . 
9. 3. 7  Peri p her al S we pt -S o urce O C T or  Peri p her al E n h a nce d  De pt h  I m a gi n g ( E DI) 
O C T  
T he reti na, c h or oi d, s u prac h or oi dal s pa ce, a n d scl era o ver t he area of treat me nt i nstillati o n 
will be assesse d usi n g peri p heral S S -O C T or peri p heral E DI -O C T i n t he st u d y e ye at 
e q ui p pe d sites.  
At t he scree ni n g visit, t he Wee k 1 2, t he Wee k 2 4, a n d Wee k 5 2/ E O S/ E T visit, b ot h e yes will 
be assesse d . St u d y e ye will be i ma ge d at all ot her visits. F urt her details are i ncl u de d i n t he 
i ma gi n g ma n ual. 

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F or s pecific g ui da nce o n sc he d uli n g of peri p heral O C T  assess me nts  i n t he o perati o nal 
alter nati ves N o. 1 -N o. 3 see Ta ble 3  f or Part A, a n d Ta ble 4  f or Part B. 
9. 3. 8  A nteri or Se g me nt O C T  (i n P art A o nl y) 
T he c h or oi d, s u prac h or oi dal s pace, a n d sclera i n t he area of i nserti o n site will be e x pl ore d 
usi n g A S -O C T  i n Part A o nl y at e q ui p pe d sites . At t he scree ni n g visits, b ot h e yes will be 
assesse d . T h e st u d y e ye will be assesse d  o n Visits 1, 2, 3, 4, a n d 5 as s pecifie d i n t he S o As i n 
Secti o n 1. 3 .  
F or s pecific g ui da nce o n sc he d uli n g of A S -O C Ts i n t he o perati o nal alter nati ves N o. 1 -N o. 3 
see Ta bl e 3  f or Part A, a n d Ta ble 4  f or Part B. F urt her details are i ncl u de d i n t he i ma gi n g 
ma n ual.  
9. 3. 9  C ol or F u n d us P h ot o gr a p h y  
Reti nal a nat o m y will be e val uate d b y C ol or  F u n d us P h ot o gra p h y ( C F P)  i n Part A a n d Part B. 
C F P i n t he st u d y e ye will be ca pt ur e d at all visits, as s pecifie d i n t he S o As i n Secti o n 1. 3 . C F P 
i n t he fell o w e ye will be ca pt ure d at t he scree ni n g, Wee k 1 2, Wee k 2 4, a n d We ek  5 2 visits, as 
s pecifie d i n t he S o As i n Secti o n 1. 3 . F or s pecific g ui da nce o n sc h e d uli n g of C F P  assess me nts 
i n t he o perati o nal alter n ati ves N o. 1-N o. 3 see Ta bl e 3  f or Part A, a n d Ta ble 4  f or Part B. 
A C F P m ust be perf or me d o nce a s u bject has met f oll o w -o n treat me nt criteria i n t he st u d y e ye 
a n d bef ore f oll o w -o n tr eat me nt is gi ve n. C F P will be ca pt ur e d usi n g eit her 4 W F or U W F 
i ma gi n g met h o ds. If t hese met h o d ol o gies are n ot a vaila ble , ac q uisiti o n of  a 7-fiel d C F P c o ul d 
be c o nsi dere d wit h t he a p pr o val of t he s p o ns or’s Me dical M o nit or . F urt her details o n C F P 
i ma gi n g are i ncl u de d i n t he i ma gi n g ma n ual.  
9. 3. 1 0  Fl u orescei n A n gi o gr a p h y  
T he a nat o mical state of t he reti nal vas c ulat ure will be e val uate d b y fl u ores cei n a n gi o gra p h y 
( F A). T h e st u d y e ye will be t he tra nsit e ye. F A will be ca pt ure d a n d a n al yze d f or b ot h e yes. F A 
will be ca pt ure d usi n g eit her 4 W F or U W F i ma gi n g met h o ds.  
Fl u orescei n a n gi o gra p h y will be perf or me d at t he scree ni n g, Wee k 2 4, a n d Wee k 5 2 visits, as 
s pecifie d i n t he S o As i n Secti o n 1. 3 . F urt her details are i ncl u de d i n t he i ma gi n g ma n ual.  
 

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9. 4  
S afet y Ass ess me nts  
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o As i n Secti o n 1. 3 . 
T he f oll o wi n g assess me nts will als o pr o vi de safet y -rele va nt i nf or mati o n b ut are disc usse d i n 
ot her secti o ns: I O P ass ess me nt ( Secti o n 9 . 3.2 ), slit-la m p bi o micr osc o p y (Secti o n 9 . 3.3 ), 
dilate d  i n direct o p ht hal m osc o p y (Secti o n 9 . 3. 4), S D-O C T ( Secti o n 9 . 3. 6), a n d pre g na nc y t est 
(Secti o n 9 . 2. 4). 
9. 4. 1  A d verse E ve nt a n d A d v erse De vice Effect C ollecti o n  
At e ver y visit, t he i n vesti gat or ( or desi g n ee) will assess a n d rec or d all A Es a n d A D Es t h at 
occ ur fr o m t he ti me t he i nf or me d c o ns e nt is si g ne d u ntil t he e n d of st u d y. D urati o n (start a n d 
st o p dates), se verit y/ gra d e, o utc o me, treat me nt, a n d relati o ns hi p t o st u d y treat me nt, 
a d mi nistrati o n pr oce d ure , a n d t he st u d y de vice will be rec or de d. F or m ore d etails,  please  refer 
t o Safet y Re p orti n g of A d verse E ve nts a n d Seri o us A d verse E ve nts  wit hi n Secti o n 9 . 5. 
9. 4. 2  L a b or at or y Testi n g  
Bl o o d sa m ples f or r o uti ne cli nical la b orat or y tests will be c ollecte d at t he s cree ni n g visit 
( Visit 1, Da y -3 0  t o -2) , at Visit 1 1 ( Wee k 2 4) , a n d Visit 1 8 ( Wee k 5 2) or E n d of St u d y / Earl y 
Ter mi nati o n  visit . Scree ni n g la b orat or y tests ma y be re peate d at t he discreti o n of t he 
i n vesti gat or. Tests t o  be perf or me d at t he scree ni n g visit are: 
1.  
N o n -fasti n g c h e mistr y ( bl o o d): s o di u m, p otassi u m, c hl ori de, bicar b o nate, al b u mi n, 
al kali ne p h os p hatase, as p artate a mi n otra nsferase, ala ni ne a mi n otra nsferas e,  g a m ma-
gl uta m yl tra nsferas e  bilir u bi n direct, bilir u bi n i n direct, t otal bilir u bi n, creati ni ne, bl o o d 
urea nitr o ge n, t otal pr ot ei n, calci u m, p h os p h or us, gl uc ose, a n d he m o gl o bi n A 1c  
2.  
He mat ol o g y (c o m plete bl o o d c o u nt wit h differe nti al): w hite bl o o d cell c o u nt, re d 
bl o o d cell c o u nt, he m o gl o bi n, he mat ocrit, mea n c or p usc ular v ol u me, mea n 
c or p usc ular h e m o gl o bi n, mea n c or p usc ular he m o gl o bi n c o nce ntrati o n, re d cell 
distri b uti o n wi dt h, platele t c o u nt, a n d mea n pl atelet v ol u me 
3.  
T h yr oi d: t h yr oi d -sti m ulati n g h or m o ne  
I n a d diti o n t o t he la b orat or y testi n g at t he scree ni n g visit, o nl y he m o gl o bi n A 1c will be teste d  
at Visit 1 1 ( Wee k 2 4) a n d Visit 1 8 ( Wee k 5 2) or E n d of St u d y / Earl y Ter mi n ati o n  visit.  

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La b orat or y testi n g will b e perf or me d b y a certifie d ce ntral la b orat or y. F or details see t he 
st u d y’s la b orat or y ma n ual. 
T he i n vesti gat or m ust re vie w t he la b orat or y re p ort, d oc u me nt t he re vie w, a n d rec or d a n y 
cli nicall y si g nifica nt a b n or mal fi n di n gs . C li nicall y si g nifica nt a b n or mal fi n di n gs fr o m t he 
scree ni n g la b orat or y testi n g t hat are e x pl ai ne d b y k n o w n diseases or c o n diti o ns will be 
c o nsi dere d me di cal hist or y a n d rec or de d as s uc h o n t he me dical hist or y pa g e of t he case 
re p ort f or m ( C R F). If t h e scree ni n g la b orat or y assess me nts detect ne w, cli nicall y si g nifica nt 
a b n or mal fi n di n gs, t hat are n ot e x plai ne d b y  k n o w n  diseases or  c o n diti o ns , s uc h fi n di n gs 
s h o ul d be rec or de d as n o n-treat me nt-e mer g e nt A E . A n y cli nicall y si g nifica nt ne w or 
w orse ne d  la b fi n di n gs oc c urri n g fr o m t he ti me of st u d y i nter ve nti o n o n  at Visit 2 , Da y 0, 
s h o ul d be rec or de d as tr eat me nt-e mer ge nt A E.  T h e la b orat or y re p orts s hall be file d wit h t he 
s o urce d oc u m e nts. T he la b orat or y re p orts m ust be file d wit h t he s o urce d o c u me nts.  
If la b orat or y val ues fr o m n o n-pr ot oc ol s pecifi e d la b orat or y assess me nts perf or me d at t he 
i nstit uti o n’s l ocal la b orat or y re q uire a c h a n ge i n p atie nt ma na ge me nt or are c o nsi dere d 
cli nicall y si g nifica nt b y t he i n vesti gat or ( e. g.,  A E, or seri o us a d verse e v e nt [ S A E]) t he n t he 
res ults m ust be rec or de d i n t he C R F. 
9. 4. 3  Vit al Si g ns , Wei g ht,  a n d  Hei g ht  
Hei g ht will o nl y be meas ure d at scree ni n g. Wei g ht a n d vital si g ns will be assesse d  at 
scree ni n g, Wee k 2 4, a n d Wee k 5 2. Vital si g ns i ncl u de meas uri n g b o d y te m perat ur e, bl o o d 
press ure after 5 mi n of sitti n g i n a rela xe d p ositi o n, a n d heart rate. If bl o o d press ure v al ues 
w o ul d re n der s u bj ects n ot eli gi ble per e xcl usi o n criteri o n N o. 3 0  at scree ni n g , at t he sa me visit 
o r later ( b ut wit hi n t he scree ni n g wi n d o w of u p t o 3 0 da ys), re p eat ass ess me nts c o ul d be 
perf or me d t o e xcl u de te m p oraril y e xa g g erate d val ues. S u bj ects are as k e d t o refrai n fr o m 
c o ns u mi n g a n y caffei nat e d be vera ges at least 3 0 mi n utes pri or t o bl o o d press ure a n d p ulse 
meas ure me nts.  
9. 5  
S afet y Re p orti n g of A d verse E ve nts a n d Seri o us A d verse E ve nts  
All s u bjects e nr olle d i n t he st u d y treat me nt will be assesse d f or safet y. 
I n vesti gat ors are res p o nsi ble f or m o nit ori n g t he safet y of s u bjects w h o ha v e e ntere d t his st u d y 
a n d f or al erti n g t he S p o ns or re gar di n g a n y e v e nt t hat see ms u n us ual, e ve n if t his e ve nt ma y be 

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c o nsi dere d a n u na ntici pat e d be nefit t o t he s u bject. T he I n vesti gat or is r es p o nsi ble f or 
a p pr o priate m e dical c are of s u bjects d uri n g t he st u d y.  
T he defi niti o ns of a d vers e e ve nts ( A Es) a n d seri o us a d verse e ve nts ( S A Es) acc or di n g t o 
c orres p o n di n g l oc al re g ul ati o ns ca n be f o u n d i n Secti o n 1 1 . 2. 
T he defi niti o ns of de vic e -relate d s afet y e ve nts, a d verse de vi ce effects ( A D Es), a n d seri o us 
a d verse d e vice effects ( S A D Es) ca n be f o u n d i n S ecti o n 1 1. 2. 1 0  a n d i ncl u d e re q uir e me nts of 
re g ulati o ns i n t he U S a n d E ur o pe. De vi ce deficie ncies are disc usse d i n Secti o n 1 1 . 2. 4. 
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or 
f oll o wi n g u p o n all AE s or  A D Es . T his i ncl u des e ve nts re p orte d b y t he s u bject ( or, w he n 
a p pr o priate, b y a care gi v er, s urr o g ate, or t he s u bject’s le gall y a ut h orize d re prese ntati ve).  
T he met h o d of rec or di n g, e val uati n g, a n d ass essi n g t he ca usalit y of A E s, S A Es , AD Es , a n d 
S A D Es  a n d t he pr oce d ures f or c o m pleti n g a n d tr a ns mitti n g c orres p o n di n g re p orts are 
pr o vi de d i n Secti o n 1 1 . 2. 
9. 5. 1  Ti me Peri o d a n d Fre q ue nc y of S afet y I nf o r m ati o n  
All A E s a n d S A Es will be c ollecte d fr o m t he si g ni n g of t he I C F u ntil t he E O S visit ( Wee k 5 2) 
at t he ti me p oi nts s pecifie d i n t he S o A s (Secti o n 1. 3 ). T he A E s a n d S A Es t hat be gi n bef ore t he 
start of st u d y i nter ve nti o n b ut after o btai ni n g I C F w here t he s e verit y di d n ot w orse n after t he 
start of st u d y i nter ve nti o n will be c ollecte d as s u c h, h o we ver , c o nsi dere d n o n -treat me nt 
e mer ge nt A Es  a n d S A Es. T he A Es  a n d S A Es t hat be gi n after t h e start of t h e st u d y 
i nter ve nti o n a n d t h ose e xisti n g pre-d ose t hat w ors e ne d i n se verit y p ost -d ose will be 
c o nsi dere d tr eat me nt -e m er ge nt A Es  a n d S A Es.  
All S A Es will be rec or de d a n d re p ort e d t o t he s p o ns or or desi g nee i m me di atel y a n d u n der n o 
circ u msta nce s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n Secti o n 1 1 . 2. T he i n vesti gat or will 
s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs of it bei n g a vaila ble. F or 
ti meli nes of re p orti n g t o re g ulat or y a ut h orities or I R Bs/ EC s, see Secti o n 1 1 . 2. 
I n vesti gat ors are n ot o bli gate d t o acti vel y se e k i nf or mati o n o n A Es  or S A Es after t he 
c o ncl usi o n of st u d y parti ci pati o n. H o we ver, if t he i n vesti gat or lear ns of a n y S A E, i ncl u di n g 
deat h, at a n y ti me after a s u bject has bee n disc h ar g e d fr o m t he st u d y, a n d t he i n vesti gat or 

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c o nsi ders t he e v e nt t o be reas o na bl y r elate d t o t he st u d y i nter ve nti o n or st u d y partici pati o n, 
t he i n vesti gat or m ust pr o m ptl y n otif y t he s p o ns or. 
9. 5. 2  Met h o d of Detecti n g S afet y E ve nts  
Care will be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A Es  a n d/ or S A Es. O pe n -e n d e d a n d 
n o n -lea di n g ver bal q uesti o ni n g of t he s u bject is t he preferre d met h o d t o i n q uire a b o ut A E 
occ urre nces.  
9. 5. 3  F oll o w -u p of S afet y E ve nts  
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr o acti vel y f oll o w eac h s u bject 
at s u bse q ue nt visits/c o ntacts. All S A Es (as defi ne d i n Secti o n 1 1 . 2.8 ) will be f oll o we d u ntil 
res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, or t he s u bject wit h dra ws t he 
i nf or me d c o nse nt or is l ost t o f oll o w-u p (as defi ne d i n Secti o n 8 .3 ). F urt her i nf or mati o n o n 
f oll o w-u p pr oce d ures is pr o vi de d i n Secti o n 1 1 . 2. 11 ). 
9. 5. 4  Re g ul at or y Re p orti n g Re q uire me nts of Seri o us S afet y E ve nts  
T he s p o ns or has a l e gal r es p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a g e ncies a b o ut t he safet y of a st u d y tr eat me nt u n der cli nical i n v esti gati o n. T he 
s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ul at or y re q uire m e nts relati n g t o safet y re p orti n g 
t o t he re g ulat or y a ut h orit y, I R Bs/I E Cs, a n d i n vesti gat ors. 
Safet y re p orti n g t o t he re g ulat or y a ut h orities will be perf or me d acc or di n g t o t he f oll o wi n g 
re g ulati o ns a p plica ble t o t he U S a n d t he E U (als o descri be d i n Secti o n 9. 5 ): 
•  I N D safet y re p orti n g G ui da nce f or I n d ustr y a n d I n vesti gat ors –  Safet y Re p orti n g 
Re q uire me nts f or I N Ds a n d B A/ B E St u dies (U S F D A 2 0 1 2 )  
•  G ui da nce S p o ns or Res p o nsi bilities –  Safet y Re p orti n g Re q uire me nts a n d Safet y 
Assess me nt f or I N D a n d Bi oa vaila bilit y/ Bi oe q ui vale nce St u dies f or I n vesti gat ors (U S 
F D A 2 0 2 1a ) a n d S p o ns ors  (U S F D A 2 0 2 1 b ) 
•  Detaile d g ui da nce o n t he c ollecti o n, verificati o n , a n d prese ntati o n of a d v erse 
e ve nt/reacti o n re p orts arisi n g fr o m cli nical trials o n me dici nal pr o d ucts f or h u ma n use 
fr o m t he E ur o pea n cli nic al trials directi ve (T h e E ur o pea n Parlia m e nt a n d t h e C o u ncil 
of t he E ur o pea n U ni o n 2 0 1 1 ) 
•  T he Cli nical Trials Directi ve 2 0 0 1/ 2 0/ E C  (T he E ur o pea n Parlia m e nt a n d t h e C o u ncil 
of t he E ur o pea n U ni o n 2 0 0 1 ) 

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•  Fr o m t he E U M e dical De vice C o or di nati o n Gr o u p: M D C G 2 0 2 0 -1 0/ 1 Safet y re p orti n g 
i n cli nical i n vesti gati o ns of me dical de vices u n der t he Re g ulati o n ( E U) 2 0 1 7/ 7 4 5 
(Me dical D e vice C o or di n ati o n Gr o u p ( M D C G) 2 0 2 0 ) a n d t he E ur o pea n Me dical 
De vice Directi ve  (E ur o p ea n Parlia me nt/ C o u ncil ( E C) 2 0 1 7 ) 
T he detaile d i nf or m ati o n o n safet y re p orti n g ti meli nes a n d pr ocesses acc or di n g t o t he 
a b o ve re g ul ati o ns will be  o utli ne d  i n Safet y M o nit ori n g Pla n,   
9. 5. 5  C o ntr ace pti o n G ui d a nce  
M ulti ple c o h orts a n d cas e -c o ntr ol st u dies i n h u ma ns s u g gest t hat mater nal c ortic oster oi d use 
s pecificall y d uri n g t he first tri mester i ncreas es t he rate of cleft li p wit h or wit h o ut cleft palate 
fr o m a b o ut 1/ 1 0 0 0 i nfa nts t o 3- 5/ 1 0 0 0 i nfa nts. T w o pr os pecti v e case -c o ntr ol st u dies s h o we d 
decrease d birt h w ei g ht i n i nfa nts e x p ose d t o mater nal c ortic oster oi ds i n uter o. H u ma n a n d 
a ni mal st u dies s u g gest a n i ncreas e d ris k f or i ntra ut eri ne gr o wt h r estricti o n a n d decrease d birt h 
wei g ht. A n i n de pe n d e nt o ver vie w a n d dis c ussi o n of t hese effects were rece ntl y c o m pile d als o 
b y Ba n d oli et al. (Ba n d oli et al., 2 0 1 7 ). 
Acc or di n gl y, a n d f oll o wi n g t he g ui da nce o n c o ntr ace pti o n of t he Cli nical Trial Facilitati o n 
Gr o u p  (Cli nical Trials Facilitati o n a n d C o or di nati o n Gr o u p 2 0 2 0 ), t he f oll o wi n g c o ntrace pti o n 
g ui da nce nee ds t o be i m ple me nte d i n t his st u d y a n d is als o me nti o ne d i n t he i ncl usi o n criteria 
i n Secti o n 5 . 
T he f oll o wi n g met h o ds are c o nsi dere d hi g hl y effecti ve as t he y ca n ac hi e ve a fail ure rate of 
less t ha n 1 % per year w h e n use d c o nsiste ntl y a n d c orrectl y:  
1.  
c o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n  
•  oral  
•  i ntra va gi nal  
•  tra ns der mal 
2.  
pr o gest o ge n -o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n  
•  oral  
•  i njecta ble 
3.  
i m pla nta ble 
4.  
i ntra uteri ne de vic e 
5.  
i ntra uteri ne h or m o ne-rel easi n g s yste m 

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6.  
bilateral t u bal occl usi o n  
7.  
vasect o mize d p art ner  
8.  
se x ual a bsti ne nce 
W o me n w h o are n ot p ost me n o pa usal ( i.e., at least 1 2 
m o nt hs of n o n -t hera p y-i n d u ce d 
a me n orr hea or s ur gicall y sterile (a bse nce of o v aries a n d/ or uter us) ) m ust a gree t o re mai n 
a bsti ne nt or us e c o m bi ne d c o ntrace pti ve met h o ds t hat res ult i n a fail ure rat e of less t ha n 1 % per 
year fr o m t he treat me nt visit (Visit 2, Da y  0) u ntil t he e n d of trial partici pati o n, or , if s u bjects 
disc o nti n ue trial partici pati o n bef ore Wee k 5 2 , f or at least 5 2  wee ks fr o m t he treat me nt visit 
(Visit 2, D a y 0).  
S o me f or ms of c o ntr ace pti o n, (e. g., h or m o nal c o ntrace pti o n) nee d t o b e starte d bef ore t h e 
treat me nt visit ( Da y 0) t o ha ve f ull effect fr o m t he ti me of e x p os ure o n. 
Males m ust a gree t o use a barrier met h o d of c o ntrace pti o n starti n g fr o m t he treat me nt visit 
(Visit 2, Da y  0) u ntil t he e n d of trial partici pati o n, or , if s u bjects disc o nti n ue trial partici pati o n 
bef ore Wee k 5 2 , f or at least 5 2  wee ks fr o m t he treat me nt visit ( Visit 2, D a y 0).  
Male s u bjects m ust defer fr o m s per m d o nati o n f or t he d urati o n of t he st u d y a n d / or 5 2  wee ks  
after recei vi n g t he st u d y treat me nt , w hic h e ver is l o n ger. 
9. 5. 6  A d verse E ve nts of S peci al I nterest  
I n t his trial, a d verse e ve nts of s pecial i nterest ( A E SIs) are d efi ne d a n d m o nit ore d f oll o wi n g 
t he sa me e x pe dite d re p orti n g as use d f or S A Es (see Secti o n 1 1. 2 ). A E SI c o m prise t he 
f oll o wi n g pres pecifi e d ter ms base d o n ge n eral c o nsi derati o ns o n p ote ntial safet y ris ks wit h 
s u prac h or oi dal d e vice d e pl o y me nt a n d treat me nt. 
1.  
S u prac h or oi dal he m orr ha ge  
2.  
Sterile i ntra oc ular i nfla m mati o n  
3.  
E n d o p ht hal mitis  
4.  
C h or oi dal bacterial i nf ecti o n  
5.  
Reti nal detac h me nt  
6.  
Reti nal perf orati o n  
7.  
Rise of I O P a b o ve 3 0 m m H g *  
8.  
Rise of at least 1 0 m m H g fr o m baseli ne I O P *  
9.  
Se vere pai n or disc o mf ort after a d mi nistrati o n of I P  

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A n A E SI of “se vere pai n or disc o mf ort after a d mi nistrati o n of I P”  s h o ul d be re p ort e d w he n a 
s u bject i n dicates se vere p ai n or disc o mf ort aft er c o m pleti o n  of t he i njecti o n pr oce d ure. Pai n 
or disc o mf ort d uri n g  t he pr oce d ure are re p orte d  se paratel y as A Es. F or ass essi n g t he 
occ urre nce of t he A E SI of “se vere pai n or disc o mf ort after a d mi nistrati o n of I P”, t he a ns w ers 
i n t he S u bject’s E x perie n ce Ass ess me nt Q uesti o n n aires s h o ul d be c o nsi dere d (see Secti o n  
1 2. 1 ) 
To c o nsi der a n ac ute I O P rise after t he treat me nt a d mi nistrati o n pr oce d ure , as a n A E SI , t h e 
rise m ust c o nti n ue be y o n d t he 6 0 mi n o bser vati o n peri o d o n Visit 2, Da y 0  or re q uire m e dical 
i nter ve nti o n, e. g., a parace ntesis t o l o wer I O P. A  rise of I O P w o ul d q ualif y as a n A E SI , w he n 
it is: 
a)  ne wl y detect e d at f oll o w -u p visits after Visit 2, D 0,  
b)  t he rise is persiste nt a n d,  
c)  t he rise is o bser ve d  o v er  at least  2 s uccessi ve sc he d ule d st u d y visits . 
9. 5. 7  Pre g n a nc y  
Details of all pre g n a ncies i n fe male s u bjects a n d fe male part ners of male s u bjects will be 
c ollecte d after t he start of t he st u d y i nter ve nti o n a n d u ntil t he c o m pleti o n of t he st u d y.  
If pre g n a nc y is re p orte d, t he i n vesti gat or will rec or d pre g na n c y i nf or mati o n o n t he a p pr o priat e 
f or m a n d s u b mit it t o t he s p o ns or wit hi n 2 4 h o urs of lear ni n g of t he pre g n a nc y. T his i ncl u des 
t he fe male s u bject or fe male part ner of a m ale s u bj ect (after o btai ni n g t he necessar y si g ne d 
I C F fr o m t he fe male p art ner). 
W hile pre g na n c y itself is n ot c o nsi dere d t o be a n A E or S A E, a n y pre g na n c y c o m plicati o n or 
electi ve ter mi nati o n of a pre g na nc y f or me dical reas o ns will be re p orte d as a n A E or S A E.  
A b n or mal pre g n a nc y o ut c o mes ( e. g., s p o nta n e o us a b orti o n, fetal deat h, still birt h, c o n ge nital 
a n o malies, ect o pic pre g n a nc y) are c o nsi dere d S A Es a n d will be re p ort e d as s uc h. A n y p ost -
st u d y pre g na nc y-relat e d S A E c o nsi dere d reas o n a bl y relate d t o t he st u d y i nter ve nti o n b y t he 
i n vesti gat or will be re p orte d t o t he s p o ns or as descri be d i n Secti o n 1 1 . 2. 
T he s u bject/ pre g n a nt fe m ale part ner will be f oll o we d t o deter mi ne t he o utc o me of t he 
pre g na nc y. T h e i n vesti gat or will c ollect f oll o w -u p i nf or mati o n o n t he s u bject/ pre g na nt f e male 
part ner a n d t he ne o n ate (after o btai ni n g a si g nat ure of pre g n a nc y f oll o w-u p s pecific I C F) a n d 
t he i nf or mati o n will be f or war de d t o t he s p o ns or. 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 11 8  of  1 6 9  
A n y fe male s u bject w h o bec o mes pre g na nt w hile partici pati n g i n t he st u d y will n ot be treate d 
wit h t he st u d y i nter ve nti o n w he n t he pre g na nc y b ec o mes a p p are nt b ef ore treat me nt 
a d mi nistrati o n at V 2. If pre g na nc y is d etecte d after a d mi nistrati o n of st u d y treat me nt, t he 
s u bject will be offere d t o atte n d st u d y visits f or a safet y f oll o w -u p wit h n o n -i n vasi ve 
assess me nts o nl y (as sta n dar d at t he rele va nt site f or t he assess me nt of pre g na nt patie nts).  
9. 5. 8  Dise ase -R el ate d E ve nts a n d/ or O utc o mes n ot Q u alif yi n g as S afet y E ve nts  
N o s pecific dise ase -relat e d e ve nts n ot q ualif yi n g as A Es or S A Es are d efi n e d f or t his cli nical 
trial. A si g nifica nt a n d u n e x pecte d l oss i n V A or para meters i n dicati n g a n i ncreas e of mac ular 
e de ma ma y b e re p orte d as A E if t he e xt e nt is si g nifica nt or u ne x p e cte d i n t h e o pi ni o n of t he 
i n vesti gat or or s p o ns or. N o n -i m pr o ve me nt or w orse ni n g of diseas e lea di n g t o t he nee d f or 
f oll o w-o n treat me nt ( as d efi ne d i n Secti o n  7 . 5. 2) w o ul d o nl y q ualif y as a n A E, if si g nifica nt 
or u ne x pect e d i n t he o pi ni o n of t he i n vesti gat or.  
9. 5. 9  Me dic al De vic e Defi cie ncies  
O x ul u mis ®  o p ht hal mic a d mi nistrati o n de vices are bei n g pr o vi de d f or us e i n t his st u d y t o 
a d mi nister D E X As p here ® as part of t he st u d y i nt er ve nti o n.  
De vice d eficie n c y is defi ne d i n I S O 1 4 1 5 5: 2 0 2 0 as a n y i na de q uac y i n t he i de ntit y, q ualit y, 
d ura bilit y, relia bilit y, safet y, or perf or ma n ce of a n i n vesti gati o nal de vice, i ncl u di n g 
malf u ncti o n, use err ors, or i na de q uac y i n t he i nf or mati o n s u p plie d b y t he ma n ufact ur er.  
To f ulfill re g ulat or y re p orti n g o bli gati o ns w orl d wi de, t he i n vesti gat or is res p o nsi ble f or t he 
detecti o n a n d d oc u m e ntati o n of e ve nts meeti n g t he defi niti o ns of de vice d eficie nc y t hat occ ur 
d uri n g t he st u d y wit h s uc h de vices.  
A n y de vice d eficie n cies o bser ve d d uri n g t he dr u g a d mi nistrati o n pr oce d ure t o cli nical trial 
s u bjects will be d oc u me nte d b y t he s p o ns or, f oll o we d-u p f or r o ot -ca use, a n d i ncl u de d i n t he 
de vice ris k ass ess me nt wit h a n e val uati o n f or t he nee d t o i m ple me nt a d di ti o nal ris k 
miti gati o ns.   
F urt her defi niti o n s re gar di n g de vice defi cie nc ies as well as pr ocesses a n d ti me peri o ds f or 
detecti o n, n otificati o n, re p orti n g, a n d f oll o w-u p  of t he me dical de vice defi cie ncies  ca n b e 
f o u n d i n Secti o n 1 1. 2 . 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 11 9  of  1 6 9  
N O T E: Defici e ncies f ulfilli n g t he defi niti o n of a n A E/ S A E will f oll o w t he pr ocesses 
o utli ne d i n Secti o n 1 1. 2. 1 1  of t he pr ot oc ol.  
9. 6  
P h ar m ac o ki netics  
P K e val uati o ns i n t he c o nte xt of t his trial are c o nsi dere d mai nl y safet y para meters t o e val uate 
p ote ntial s yste mic e x p os ure aft er s u prac h or oi dal a d mi nistrati o n. P K e val uati o ns ar e n ot 
e x pecte d t o pr o vi d e  s urr o gates f or t hera pe utic effects. 
W h ole bl o o d sa m ples of a p pr o xi matel y 5 m L will be c ollecte d f or meas ure me nt of plas ma 
c o nce ntr ati o ns of st u d y i nter ve nti o n o n Visits 1, 2, 3, 4, 5 , 1 1 , a n d 1 8 (scree ni n g, Da y 0 
[6 0 mi n  after a d mi nistrati o n of t he st u d y treat me nt], a n d Da y 1, wee k 1, 4, 2 4 a n d 5 2 visits, 
res pecti vel y) as s pecifie d i n t he S o A (Ta ble 1  –  Part A ) t o ass ess s yste mic e x p os ure of 
de xa met has o ne after a d mi nistrati o n of O X U -0 0 1  f or partici pa nts i n Part A o nl y. O n Visit 2, 
Da y  0, after t he a d mi nistrati o n of st u d y treat me nt, bl o o d sa m ples ma y be o btai ne d later t ha n 
6 0 mi n  after a d mi nistrati o n , b ut t he e xact ti me has t o be rec or de d. F or s u bjects recei vi n g 
f oll o w-o n treat me nt wit h I V T ster oi ds, P K sa m ples ta ke n fr o m t he ti me of a d mi nistrati o n of 
t his ster oi d f oll o w-o n treat me nt will n ot be c o nsi dere d as refl ecti n g P K of t he i nitial st u d y 
treat me nt. 
P har mac o ki netic dat a a n al ysis will be c o n d ucte d usi n g sta n dar d n o nc o m part me ntal met h o ds 
of a nal ysis wit h a P K s oft ware pr o gra m t hat meets or e xcee ds mi ni m u m s yste m re q uire me nts. 
T he versi o n of t he s oft ware use d f or t he a n al ysis will be d oc u me nte d, a n d t h e pr o gra m will 
meet t he re q uir e me nts of s oft ware v ali dati o n.  
Atte m pts s hall be ma de t o a d here t o t he s c he d ule d c ollecti o n ti mes, b ut it is rec o g nize d t hat 
sit uati o ns ma y arise t hat ma y c o m pr o mise t he sc h e d ule f or sa m ple c ollecti o ns. Para meters 
will be i n di vi d uall y calc ulate d f or eac h s u bject bas e d o n act ual c ollecti o n ti mes a n d prese nte d 
b y s u m mar y statistics.  
T he desi g n a n d met h o ds f or statistical a nal yses of t he p har mac o ki n etic data are pr o vi d e d i n 
Secti o n 1 0. 4. 4  a n d will be detaile d i n t he S A P. 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 2 0  of  1 6 9  
1 0  St atistic al C o nsi der ati o ns  
T his is a P hase 2 st u d y desi g ne d t o pri maril y assess t he safet y of t he e x peri me ntal 
i nter ve nti o n. Descri pti ve s u m maries of safet y, cli nicall y (e. g., mea n B C V A c ha n ge fr o m 
baseli ne), a n d a nat o micall y ( e. g., mea n C S T c ha n g e fr o m baseli ne) rel e va nt o utc o me 
meas ures will be prese nt e d. E x pl orat or y a n al yses will be perf or me d t o c o m pare t he effi cac y 
of t he e x peri me ntal i nter ve nti o n, i.e., t w o d oses of O X U-0 0 1 i n Part  A, a n d  B of t he trial, t o  i n 
Part B  t he acti ve c o m parat or, Oz ur de x. 
T he Statistical A nal ysis Pla n ( S A P) will be fi nalize d pri or t o dat a base l oc k, a n d it will i ncl u de 
a m ore tec h ni cal a n d d etaile d descri pti o n of t he statistical a nal yses descri b e d i n t his secti o n.  
1 0. 1  St atistic al H y p ot hesis  
As t he prese nt trial is pri maril y desi g ne d t o assess safet y, n o f or mal statistical h y p ot hesis 
testi n g will be perf or me d f or Part A a n d Part B. 
1 0. 2  S a m ple Size Deter mi n ati o n  
F or Part A of t he sa m ple size of 1 8 s u bjects is c o nsi dere d a d e q uate t o f ulfill t he o bjecti ves of 
t his i nitial part of t he trial. Ei g htee n ( 1 8 ) s u bjects are e x p ecte d t o b e s uffi cie nt t o detect 
c o m m o n a n d ver y c o m m o n a d verse e ve nts (s p ecificall y i ncreas es of I O P) t o pr o vi de safet y 
i n p ut o n t he d oses f or Part B (see als o Secti o n 7. 5. 1 ). Ra n d o mize d s u bjects i n w h o m st u d y 
treat me nt ca n n ot b e a d mi nistere d will be re place d. 
F or Part B of t his cli nical trial, t he ra n d o mizati o n sc he me is 2: 2: 1. Ar m B 3, t he Oz ur de x ®  ar m 
will o nl y half t he n u m ber of s u bjects c o m pare d t o t he O X U -0 0 1 Ar ms B 1 a n d B 2, t o 
mi ni mize e x p os ure t o t he e x pecte dl y m or e fre q ue nt ster oi d si de effects ass o ciate d wit h 
Oz ur de x ® . T h e sa m ple si ze was d eter mi ne d pri maril y base d o n esti mati n g t he treat me nt effect 
a n d safet y pr ofile of O X U -0 0 1 t o o btai n i nf or mati ve data f or desi g ni n g f urt her trials wit h a 
pi v otal i nte nt.  Ra n d o mize d s u bjects i n w h o m st u d y treat me nt ca n n ot b e a d mi nistere d will be 
re place d. 
I V T a d mi nistrati o n of Oz ur de x®  res ults i n pea k effects (i n ter ms of b ot h i ncrease d vis ual 
ac uit y a n d re d u ce d C S T) a b o ut 2 m o nt hs after treat me nt wit h a ret ur n t o le v els near baseli ne 
b y m o nt h 6. U n der t his pr ofile a n d t he f oll o w -o n treat me nt criteri a defi ne d i n Secti o n 7. 5. 2 , 
cli nical e x peri e nce b ase d o n o utc o mes wit h cli nical trials usi n g t he a p pr o ve d 6 -m o nt h 
treat me nt i nter val (B o yer et al., 2 0 1 4 ) or s h orter i nter vals li ke 1 6 wee ks  (Fraser -Bell et al., 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 2 1  of  1 6 9  
2 0 1 6 ; A u g usti n et al., 2 0 2 1 ) s u g gest t hat a lar g e pr o p orti o n of patie nts i n t he Oz ur de x ®  ar m 
will re q uire f oll o w -o n tr eat me nt b y m o nt h 6 (esti mate d at 7 5 %, 8 0 %, a n d 8 5 % i n  Ta ble 1 2 ). 
Pre -cli nical data s u g g est t hat s u prac h or oi dal a d mi nistrati o n of O X U -0 0 1 lea ds t o si milar 
pea ks at M o nt h 2. Ass u mi n g t hat t he treat me nt effect f or O X U -0 0 0 1 is sta ble f or at least 
6  m o nt hs, t he pr o p orti o n of patie nts re q uiri n g f oll o w -o n treat me nt b y 6 m o nt hs i n t he 
O X U  0 0 1 ar ms is e x p ect e d t o be s maller t ha n t hat i n t he Oz ur de x ®  ar m. Ta ble 1 2  s h o ws t he 
ma xi m u m para meter val ues of 2 4 -w ee k  f oll o w-o n treat me nt pr o ba bilities i n a n O X U -0 0 1 ar m 
t hat yiel d 8 0 % p o wer t o reject t he n ull h y p ot hesis ( of e q ual 6-m o nt h f oll o w -o n treat me nt 
pr o ba bilities) wit h Fis her’s e xact test ( 2 -si de d, Ty p e 1 err or c o ntr olle d at 1 0 % a n d sa m ple 
sizes of 2 2 a n d 4 4 f or t he Oz ur de x ®  a n d O X U-0 0 1 ar ms, res pecti vel y).  
Ta ble 1 2  Pr o b a bilit y of f oll o w -o n tre at me nt b y Wee k 2 4 f or Oz ur de x ®  
 
Pr o ba bilit y of f oll o w -o n treat me nt b y Wee k 2 4  f or Oz ur de x ®  
*  
7 5 %  
8 0 %  
8 5 %  
Ma xi m u m pr o ba bilit y f or 
O X U -0 0 1 t hat yiel ds at 
least 8 0 % p o wer 
4 1 %  
4 6 %  
5 2 %  
*( Ra n ge of para met er val ues ( pr o ba bilit y of f oll o w -o n treat me nt b y Wee k 2 4 ) f or a n 
O X U -0 0 1 d ose t hat yiel ds > 8 0 % p o wer f or a 2 -sa m ple c o m paris o n of pr o p orti o ns ( 2-si de d 
Fis her’s e xact test, 𝛼= 0 .1 , sa m ple sizes 2 2 a n d 4 4 f or Oz ur de x®  a n d O X U-0 0 1 ar ms 
res pecti vel y). 
A nal o g o usl y, f or a n e x pl orat or y a n al ysis c o m pari n g t he fre q u e nc y of safet y e ve nts i n o ne of 
t he O X U-0 0 1 ar ms t o t he Oz ur de x ®  ar m, Ta ble 1 3  s h o ws t he ma xi m u m pr o ba bilit y of e ve nts 
i n t he O X U-0 0 1 ar m t hat will yiel d 8 0 % p o wer usi n g a 2 -si de d Fis her’s E x act Test ( T y p e 1 
err or c o ntr olle d at 1 0 %) t o reject t he n ull h y p ot hesis t hat t he fre q ue n c y wit h w hic h a d verse 
safet y e v e nts occ ur is e q ual i n b ot h ar ms. 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 2 2  of  1 6 9  
Ta ble 1 3  Pr o b a bilit y of A d verse S afet y E ve nt f or Oz ur de x ®  
 
Pr o ba bilit y of A d verse S afet y E ve nt f or Oz ur de x ®  
*  
2 5 %  
3 0 %  
3 5 %  
Ma xi m u m 
pr o ba bilit y f or 
O X U -0 0 1 t hat yiel ds 
at least 8 0 % p o wer  
2. 5 %  
4. 6 %  
7. 2 %  
* Ra n ge of para meter val ues ( pr o ba bilit y of a d v erse safet y e ve nt) f or a n O X U -0 0 1 d ose t hat 
yiel ds > 8 0 % p o wer f or a 2 -sa m ple c o m paris o n of pr o p orti o ns ( 2-si de d Fis h er’s e x act test, 
𝛼= 0 .1 , sa m ple sizes 2 2 a n d 4 4 f or Oz ur de x®  a n d O X U-0 0 1 ar ms res pecti vel y)  
1 0. 3  A n al ysis Sets  
1 0. 3. 1  F ull A n al ysis Set  
T he F ull A nal ysis Set ( F A S) p o p ulati o n will i ncl u de all ra n d o mize d s u bj ects w h o recei v e d t he 
st u d y treat me nt a n d ha v e at least o ne p ost-bas eli ne efficac y o bser vati o n or meas ure me nt. 
S u bjects will be a nal yze d acc or di n g t o t he st u d y tr eat me nt gr o u p t o w hic h t he y were 
ra n d o mize d.  
1 0. 3. 2  Per Pr ot oc ol Set  
T he Per Pr ot oc ol S et ( P P S) c o nsists of t he F A S p o p ulati o n wit h e xce pti o n of s u bjects wit h 
i m p orta nt pr ot oc ol vi olati o ns t hat c o ul d i nfl ue nce t he vali dit y of t he data f or t he pri mar y 
effic ac y e v al uati o ns. I n t he a nal yses b ase d o n P P S, s u bjects will be a nal yze d acc or di n g t o t he 
ra n d o mize d st u d y treat me nt gr o u p. All criteria t o e xcl u de s u bjects fr o m t he P P S will be ma de 
base d o n a mas k e d re vie w of t he data pri or t o t he u n mas ki n g of t he trial f or t he Wee k  2 4  
a nal ysis.  
1 0. 3. 3  S afet y  A n al ysis Set  
T he Safet y A nal ysis Set ( S A S) will i ncl u de all s u bjects i n w h o m t he a d mi nistrati o n of st u d y 
treat me nt was starte d (re gar dless of w h et her t he s u bjects were recr uite d i n Part A or Part B). 
I n a nal yses perf or m e d o n t he Safet y A nal ysis Set, s u bjects will be a nal yze d acc or di n g t o t heir 
act ual treat me nt recei ve d.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 2 3  of  1 6 9  
1 0. 3. 4  P h ar m ac o ki netics ( P K) A n al ysis Set  
P K A nal ysis Set ( P K S) p o p ulati o n will i ncl u de s u bjects e nr olle d i n Part A of t he st u d y w h o 
ha ve recei ve d st u d y dr u g a n d f or w h o m at least o ne P K sa m ple has bee n a n al yze d a n d wit h n o 
maj or pr ot oc ol de viati o ns t hat ha ve P K i m plicati o ns.  
1 0. 4  St atistic al A n al yses  
1 0. 4. 1  Ge ner al C o nsi der ati o ns  
All statistical a nal yses will be o utli ne d i n detail i n a n  S A P w hic h will be pre pare d a n d si g n e d 
pri or t o data base l o c k or a n y st u d y -s pecific a nal ys es. S u m mar y statistics fr o m i n vesti gat or 
fi n di n gs will be ta b ulate d a n d s u m marize d d escri pti vel y. All c o nti n u o us meas ures will be 
s u m marize d descri pti vel y, i ncl u di n g t he n u m ber of a vaila ble val ues, mi ni m u m, 1st q uartile, 
me dia n, mea n, sta n dar d de viati o n, 3r d q uartile, m a xi m u m, a n d 9 5 % c o nfi d e nce i nter val f or 
t he mea n, if a p pr o priate. Cate g orical data will be prese nte d b y fre q u e nc y a n d perce nt a ge. 
Or di nal rati n gs ma y be h a n dle d as c o nti n u o us dat a if a p pr o pri ate or prese nte d as cate g orical if 
t he n u m ber of cate g ories is s mall. 
1 0. 4. 2  S afet y A n al ysis  
All safet y a nal yses will be perf or me d o n t he S A S p o p ulati o n.  
T he treat me nt -e mer g e nt A Es/ A D Es ( defi n e d as a n y A E occ urri n g or w ors e ni n g wit h t he sa me 
date or later t ha n t hat of t he first a p plicati o n of st u d y treat me nt) will be e n c o de d usi n g t he 
Me d D R A  dicti o nar y.  
T he treat me nt -e mer g e nt A Es or A D Es will use t he s yste m or ga n cl ass ( S O C) a n d preferre d 
ter m ( P T) c o des. T he treat me nt-e mer g e nt A Es or A D Es will be s u m marize d b y S O C a n d P T. 
B ot h t he n u m ber a n d perce nta ge of s u bjects w h o e x perie n ce t he e ve nt a n d t he n u m ber of 
e ve nts will be s u m marize d.  
T E A Es, st u d y dr u g -rel ate d A Es, A Es of S pecial I nterest ( A E SIs), A Es le a di n g t o wit h dra wal 
fr o m t he st u d y, S A Es, a n d seri o us A D Es will be s u m marize d si milarl y. A Es will be prese nte d 
cate g oriz e d as o c ular a n d n o n -oc ular A Es. O c ular A Es will be prese nte d s e paratel y f or t he 
st u d y e ye a n d t he n o n-st u d y e ye. 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 2 4  of  1 6 9  
1 0. 4. 3  E x pl or at or y Effic ac y a n d S afet y A n al yses  
T he f oll o wi n g mai n e x pl orat or y e n d p oi nts will be descri be d o n effi cac y e v al ua ble p o p ulati o n 
a n d per-pr ot oc ol efficac y p o p ulati o n (if differe nt)  f or eac h part of t he trial s e parat el y, i.e., o ne 
a nal ysis f or eac h part : 
1.  
Ti me fr o m baseli ne ( Visit 2) t o s u bjects re q uiri n g f oll o w-o n treat me nt  ( per pre-
s pecifie d criteria). 
2.  
Mea n C ha n ge B C V A ( E T D R S) at Wee k 2 4 c o m pare d t o bas eli ne.  
3.  
Mea n C ha n ge i n c e ntral s u bfiel d t hic k ness ( C S T o n S D -O C T) at Wee k 2 4 c o m pare d 
t o baseli ne.  
4.  
Mea n C ha n ge i n B C V A ( E T D R S) t hr o u g h Wee k 5 2 c o m pare d t o bas eli ne.  
5.  
Mea n C ha n ge i n C S T o n S D -O C T  t hr o u g h Wee k 5 2 c o m pare d t o bas eli ne. 
6.  
Pr o p orti o n of s u bjects re q uiri n g f oll o w -o n treat m e nt at st u d y visits fr o m Wee k 1 2 
t hr o u g h Wee k 5 2. 
7.  
Pr o p orti o n of s u bjects wit h 5 -, 1 0-, or 1 5-letter ( E T D R S) gai n of B C V A fr o m wee k 4 
t o wee k 5 2 c o m pare d t o baseli ne. 
8.  
Pr o p orti o n of s u bjects wit h 5 -, 1 0-, or 1 5-letter ( E T D R S) l oss of B C V A fr o m wee k 4 
t o wee k 5 2 c o m pare d t o baseli ne.  
9.  
Pr o p orti o n of s u bjects wit h B C V A  > 6 8  letters ( E T D R S) at eac h st u d y visit fr o m wee k 
4 t o wee k 5 2.  
1 0.  
Mea n c ha n g e i n N EI V F Q -2 5 T otal Sc ore Wee k 2 4, a n d Wee k  5 2 c o m pare d t o 
baseli ne.  
F urt her e x pl orat or y e n d p oi nts f or Part A a n d Part B deri ve d fr o m t he assess me nts of t his trial 
will be s u m marize d i n detail i n t he S A P.  
All c o nti n u o us meas ures will be s u m marize d descri pti vel y, i ncl u di n g t he n u m ber of a v aila ble 
val ues, mi ni m u m, 1st q uartile, me dia n, mea n, sta n dar d de viati o n, 3r d q u artile, ma xi m u m, a n d 
9 5 % c o nfi de n ce i nter val f or t he mea n, if a p pr o pri ate. Cate g orical data w ill be prese nt e d b y 
fre q ue n c y a n d p erce nta g e. Or di nal rati n gs ma y be ha n dle d as c o nti n u o us d ata if a p pr o priate or 
prese nte d as cate g orical if t he n u m ber of cate g ories is s mall.  

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1 0. 4. 4  P h ar m ac o ki netics A n al yses  
Base d o n P K e val uati o n f or ot her s u prac h or oi dal, or i ntra vitreal ster oi ds as well as P K data 
fr o m testi n g of D M A a n d D X M s yste mic e x p os ure f oll o wi n g s u prac h or oi dal a d mi nistrati o n of 
D M A micr os p here f or m ulati o ns i n a ni mal m o dels, it is e x pecte d t hat t he maj orit y of data 
p oi nts reflect mi ni mal s yste mic e x p os ure or are b el o w t he l o wer le vel of q ua ntitati o n. If 
o bser ve d plas ma d e xa met has o ne c o nce ntrati o ns all o w, t he y will be use d t o calc ulate s e veral 
P K para meters, i ncl u di n g ti me t o ma xi m u m o bser ve d dr u g c o nce n trati o n (t ma x), ma xi m u m 
o bser ve d dr u g c o nce ntrati o n ( C ma x), area u n der t he c ur ve ( A U C) fr o m ti me zer o ( pre -d ose) 
t o ti me t, w here t is t he last ti me p oi nt wit h a meas ura ble c o n ce ntr ati o n [ A U C( 0-tlast)], A U C 
fr o m ti me zer o t o 6 0 mi n [ A U C( 0-6 0 mi n)], A U C fr o m ti me zer o t o o ne d a y [ A U C( 0-1 d)], 
A U C fr o m ti me zer o t o o ne wee k [ A U C( 0 -1 w)], a n d A U C fr o m ti me zer o t o eac h of t h e 
re mai ni n g ti me p oi nts. F or t he Da y 0 sa m ple, t h e e xact ti me of sa m pli n g after st u d y treat me nt 
will be rec or de d a n d t his ti me i nter val will b e use d f or cal c ulati o ns , as it ma y n ot be e xactl y 
6 0 mi n . 
P har mac o ki netics an al yses  will be descri be d i n  d etail  i n t he S AP. 
1 0. 4. 5  I m p ort a nt Pr ot oc ol Vi ol ati o ns 
Pr ot oc ol vi olati o ns will be c ollecte d a n d re vi e we d d uri n g t he trial.  
I m p orta nt pr ot oc ol vi olati o ns are defi n e d as t h ose vi olati o ns fr o m t he pr ot oc ol li kel y t o ha ve 
a n i m pact o n t he percei v e d efficac y a n d/ or safet y of st u d y treat me nts.  
E xa m ples of  i m p orta nt pr ot oc ol vi olati o ns i ncl u de: 
1.  
N ot meeti n g t he i ncl usi o n criteria or m eeti n g t he e xcl usi o n criteria, res pecti vel y  
2.  
Missi n g st u d y visits or o ut of wi n d o w st u d y visits ( de pe n di n g o n t he t y pe of visit a n d 
o n t he ti me i nter val).  
3.  
I nta k e of n o n-a ut h orize d c o nc o mita nt treat me nt  
4.  
Missi n g i m p orta nt safet y data p oi nts (I O P meas ure me nts, dilate d f u n d us e x a mi nati o ns, 
B C V A meas ure me nt, S D -O C T meas ure me nt, etc.)  

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1 0. 4. 6  Ot her A n al yses  
1 0. 4. 6. 1  S u bject Dis p ositi o n a n d B aseli ne C h ar acteristics  
S u bject dis p ositi o n will i ncl u de t he n u m ber of s u bjects w h o e nr oll i n t he st u d y a n d t he 
n u m ber a n d perce nt a ge of s u bjects i ncl u de d i n eac h a nal ysis p o p ulati o n b y treat me nt. T he 
fre q ue n c y a n d p erce nta g e of s u bjects w h o wit h dra w or disc o nti n ue fr o m t he st u d y, al o n g wit h 
t he reas o n f or wit h dra wal or disc o nti n uati o n, will be s u m marize d b y tr eat m e nt. De m o gra p hics 
a n d baseli ne c h aracteristi cs, i ncl u di n g a ge, ge n d er, a n d race will be s u m marize d usi n g 
descri pti ve statistics f or t he S A F p o p ulati o n.   
1 0. 4. 6. 2  Me dic al Hist ory  
Me dical hist or y fi n di n gs will be prese nte d b y c o u nt, fre q ue n c y, a n d perce nta ge of fi n di n gs.  
1 0. 4. 6. 3  Ot her S afety  
La b orat or y test res ult s, a n d vital si g ns  will be prese nte d b y c o u nt, fre q ue n c y, a n d perce nta ge 
of fi n di n gs.  
1 0. 4. 6. 4  C o nc o mit a nt Me dic ati o ns  
F or  pri or a n d c o n c o mita nt me dicati o ns, t he ori gi nal ter ms will be rec or de d o n t he St u d y 
S u bjects’ e C R F b y t he i n vesti gat or. Pri or a n d c o nc o mita nt me dicati o ns will be c o de d  usi n g 
W H O -D D , a n d ver bati m ori gi nal ter ms rec or de d o n t he e C R F will be prese nte d as data 
listi n gs a n d s u m mar y ta bles . 
1 0. 4. 6. 5  P h ysici a n Pr oce d ure Assess me nt  
A nal yses of t he P h ysicia n Pr oce d ure Assess me nt will be descri be d in t he S A P. 
1 0. 4. 6. 6  P atie nt E x perie nce Assess me nt  
A nal yses of t he Patie nt E x perie nce Ass ess me nt will be descri be d in t he S A P. 
1 0. 4. 7  Missi n g D at a a n d I m p ut ati o n Met h o ds  
I n case t h e start date f or a n A E/ A D E is missi n g or i nc o m plete, s o t hat it is n ot p ossi ble t o 
e val uate if it has o cc urre d pre - or p ost -tr eat me nt, t his A E/ A D E will be classifie d 
c o nser vati vel y as treat me nt -e mer g e nt.  

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S u bject s w h o will re q uire t he nee d f or t hera p y of D R c o m plicati o ns will be i m p ute d as t h ose 
re q uiri n g f oll o w-o n treat me nt . F urt her cate g orizati o ns f or i m p utati o ns ma y be e x pl ore d as 
se nsiti vit y a nal yses. 
M ore details ca n b e f o u n d i n t he st u d y S A P.  
1 1  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 1. 1  Re g ul at or y, Et hic al, A n d St u d y O versi g ht C o nsi der ati o ns  
1 1. 1. 1  Re g ul at or y a n d Et hic al C o nsi der ati o ns  
T he st u d y will be perf or me d i n acc or da nce wit h et hical pri nci ples t hat ha v e t heir ori gi n i n t he 
Declarati o n of Helsi n ki a n d are c o nsiste nt wit h I C H/ G C P a n d a p plica ble re g ulat or y 
re q uire me nts. T h e s p o ns or or t he s p o ns or’s re pres e ntati ves will o btai n re g ulator y a p pr o val 
fr o m t he c o m pete nt a ut h orit y pri or t o t he cli nical trial start. T he s p o ns or will pr o vi de all 
necessar y d oc u me nts t o o btai n s uc h a p pr o val.  
If a n y of t he d oc u me nts r ele va nt t o o btai ni n g a p pr o val are a me n de d, t he s p o ns or or t he 
s p o ns or’s re prese ntati ves will s u b mit t hese d oc u me nts f or re vi e w a n d s u bse q ue nt a p pr o val t o 
t he c o m pete nt a ut h orit y. 
A n a n n ual safet y/ pr o gress re p ort will be pr o vi de d b y t he s p o ns or or t he s p o ns or’s 
re pres e ntati ves t o t he c o m pete nt re g ulat or y a ut h orit y as re q uire d b y a p plica ble re g ulati o ns. 
T he s p o ns or or t he s p o ns or’s re prese nt ati ves will o btai n et hical a p pr o v al fr o m t he I nstit uti o nal 
Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C) pri or t o t he cli ni cal trial start. T he 
s p o ns or will pr o vi de all necessar y d oc u me nts t o o btai n s uc h a p pr o val.  
If a n y of t he d oc u me nts r ele va nt t o o btai ni n g a p pr o val is a me n de d, t he s p o ns or or t he 
s p o ns or’s re prese ntati ves will s u b mit t hese d oc u me nts f or re vi e w a n d s u bse q ue nt a p pr o val t o 
t he I R B/I E C. 
T he i n vesti gat or is res p o nsi ble f or t he acc urac y a n d c o m plete ness of all data rec or de d i n t he 
patie nt me dical c harts a n d C R Fs.  All data rec or de d i n t he C R F are deri ve d fr o m s o urce d ata 
u nless s pecificall y e x e m pte d. S o urce data will be defi ne d pri or t o t he start of t he cli nical trial 
b ut c o nsists i n ge neral of t he i nf or mati o n d oc u me nte d i n t he patie nt me dical c hart.  
C orrecti o ns t o data s h o ul d be ma de i n a wa y s o t hat t he ori gi nall y rec or de d data is still le gi ble 
a n d tracea ble. A n y c h a n g es s h o ul d be i nitiale d  a n d date d b y t he pers o n c orrecti n g t he m . T he 

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i n vesti gat or will mai ntai n a file of ess e ntial d oc u me nts of t he trial as defi n e d b y t he re g ulat or y 
re q uire me nts, I C H, a n d t he s p o ns or. 
1 1. 1. 2  Fi n a nci al Discl os ure  
Fi na ncial c o m pe nsati o n of t he i n vesti gat or a n d/ or his/ her i nstit uti o n will be re g ulate d i n a 
fi na ncial a gree me nt esta blis he d bet wee n t he s p o ns or or t he s p o ns or’s re pres e ntati ve a n d t he 
i n vesti gat or a n d/ or his/ her i nstit uti o n. 
1 1. 1. 3  I nf or me d C o nse nt Pr ocess 
F oll o wi n g I R B/I E C a p pr o val a n d bef ore a n y i n v esti gati o n -relate d pr oce d ure, p ote ntial 
s u bjects will be as ke d t o si g n a writte n I C F. T he s u bjects will be gi ve n s ufficie nt ti me f or t he 
i nf or mati o n t o be rea d a n d u n derst o o d. T he s u bject will be a p pr oac h e d a n d gi ve n t he c ha n ce 
t o as k a n y q uesti o ns t hat ha ve aris e n after rea di n g t he I C F. 
T he s p o ns or’s sa m ple I C F will be pr o vi de d t o eac h site. If a p plica ble, it will be pr o vi de d i n a 
certifie d tr a nslati o n of t he l ocal la n g ua g e. T he s p o ns or or its desi g nee m ust re vie w a n d 
a p pr o ve a n y pr o p ose d d e viati o ns fr o m t he s p o ns or's sa m ple I C Fs bef ore I R B/I E C s u b missi o n. 
T he fi nal I R B/I E C a p pr o ve d C o nse nt F or ms m ust be pr o vi de d t o t he s p o ns or f or healt h 
a ut h orit y s u b missi o n p ur p oses acc or di n g t o l ocal r e q uire me nts.  
T he C o nse nt F or ms m ust be si g ne d a n d date d b y t he s u bject bef ore his or her partici p ati o n i n 
t he st u d y. T he case hist or y or cli nical rec or ds f or eac h s u bject s hall d oc u m e nt t he I C F pr ocess 
a n d t hat writte n I C F was o btai ne d pri or t o partici p ati o n i n t he st u d y.  
S u bject s u na ble t o gi ve c o nse nt pers o nall y will o nl y be c o nse nte d i n t h ose c o u ntries w here 
nati o nal la w/re g ulati o ns per mit.  
T he C o nse nt F or ms s h o ul d be re vise d w h e ne ver t here are c ha n ges t o st u d y pr oce d ures or 
w he n ne w i nf or mati o n bec o mes a v aila ble t hat ma y affect t he willi n g ness of t he s u bject t o 
partici pate. T h e fi nal r e vise d I R B/I E C -a p pr o ve d C o nse nt F or ms m ust be pr o vi de d t o t he 
s p o ns or f or healt h a ut h orit y s u b missi o n p ur p oses. 
S u bject s m ust be re-c o ns e nte d t o t he m ost c urre nt versi o n of t he C o nse nt F or ms ( or t o a 
si g nifica nt ne w i nf or mati o n/fi n di n gs a d de n d u m i n acc or da nce wit h a p plica ble la ws a n d 
I R B/I E C p olic y) d uri n g t heir partici pati o n i n t he st u d y. F or a n y u p date d or re vise d C o nse nt 
F or ms, t he case hist or y or cli nical rec or ds f or eac h s u bject s hall d oc u me nt t he I C F pr ocess 

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a n d t hat writte n I C F was o btai ne d usi n g t he u p date d/re vise d C o nse nt F or ms f or c o nti n ue d 
partici pati o n i n t he st u d y.  
A c o p y of eac h si g ne d C o nse nt F or m m ust be pr o vi de d t o t he s u bject. All si g ne d a n d date d 
C o nse nt F or ms m ust re mai n i n eac h s u bject’s st u d y file or t he site file a n d m ust be a vaila ble 
f or verifi cati o n b y st u d y m o nit ors at a n y ti me. 
1 1. 1. 4  Recr uit me nt Str ate g y  
S u bjects i n t his cli nical trial will be recr uite d fr o m t he p o ol of patie nts at t he partici pati n g 
i n vesti gati o nal sites a n d b y referrals fr o m ge neral o p ht hal m ol o gists or o pt o metrists t o t he 
i n vesti gati o nal ce nters.  
1 1. 1. 5  D at a Pr otecti o n  
1 1. 1. 5. 1  Or g a niz ati o n al a n d Tec h nic al Arr a n ge me nts  
I n t he f oll o wi n g or ga ni zati o nal a n d tec h ni cal arra n ge m e nts are s u m marize d t hat will be 
i m ple me nte d t o a v oi d u na ut h orize d access, dis cl os ure, disse mi nati o n, alterati o n or l oss of 
i nf or mati o n, a n d pers o n al data pr ocess e d.  
Pr ocessi n g of pers o nal data s hall be carrie d o ut o n be half of t he S p o ns or b y eac h cli nical 
i n vesti gati o n site, g o ver ne d b y a c o ntract a n d strictl y acc or di n g a n d s u bject t o c o m plia nce wit h 
eac h c o u ntr y’s data pri vac y la ws, i ncl u di n g t he U nite d States’ ( U S) Healt h I ns ura nce P orta bilit y 
a n d A cc o u nta bilit y Act of 1 9 9 6 ( HI P A A), t he E ur o pea n U ni o n ( E U) Ge n eral Data Pr otecti o n 
Re g ulati o n Article 6( 1)(f) a n d Article 9( 2)(j), t he U nite d Ki n g d o m’s ( U K) Data Pr otecti o n A ct 
of 2 0 1 8, a n d a n y s u bse q ue nt a me n d me nts t o t he s e re g ulati o ns or l ocal la w e q ui vale nt t hat is 
later a d o pte d (“ Re g ulati o n”) as w ell as t h e pri v ac y a n d c o nfi d e ntialit y re q uire me nts of I C H 
G o o d Cli nical Practice ( G C P).  
All pers o nal data s hall b e treat e d as c o nfi de ntial b y t he cli nical trial sites. W he n c ollecti n g 
pers o nal d ata a n d healt hcare i nf or mati o n, t h e cli nical site s hall b e t he C o ntr oller f or t his data. 
T he cli nical site s hall utilize pse u d o n y mizati o n w here b y a u ni q ue s u bject i de ntificati o n n u m ber 
is assi g ne d t o eac h s u bject e nr olle d i n t he st u d y. T his mea ns t hat s u bject na mes are n ot i ncl u de d 
i n data sets t hat are tra ns mitte d t o a n y s p o ns or l ocati o n. T he cli nical site will mai ntai n t he ke y 
li n ki n g t he u ni q ue s u bject i de ntifier t o pers o nal i de ntif yi n g i nf or mati o n ass ociate d wit h eac h 
patie nt (“ Pse u d o n y mize d 
Data C o ntr oller”). T he s p o ns or s hall o nl y be C o ntr oller of 
a n o n y mize d data (“ A n o n y mize d Data C o ntr oller”) t hat is create d d uri n g t he cli nical trial, w hic h 

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t he cli nical trial site s hall pr ocess o n t he s p o ns or’s be half as a Pr ocess or. W he n s er vi n g as 
C o ntr oller or Pr ocess or, t he cli nical site s hall act i n acc or da nce wit h t he a p plica ble d ata 
pr otecti o n la ws.  
1 1. 1. 5. 2  C o nfi de nti ality Me as ures  
Eac h cli nical trial site s hall i m ple me nt a p pr o pri ate tec h ni cal a n d or g a ni zati o nal meas ures t o 
e ns ure a le vel of sec urit y a p pr o priate t o t he ris k, ta ki n g i nt o acc o u nt t he state of t he art, t he 
c osts of i m ple me ntati o n a n d t he nat ure, s c o pe, c o nte xt,  a n d p ur p oses of pr ocessi n g as well as 
t he ris k of var yi n g li keli h o o d a n d s e verit y f or t h e ri g hts a n d free d o ms of n at ural p ers o ns. A n y 
access t o pers o nal d ata i nf or mati o n c o ntai n e d wit hi n data bases a n d bi n ders s hall be caref ull y 
restricte d a n d o nl y vie wa ble b y a p pro priate cli nical trial staff f or le giti mate p ur p oses. Sec urit y 
pr oce d ures s hall be i n place t o pr otect a gai nst u na ut h orize d access or l oss of pers o nal data t o 
e ns ure t hat pers o nal data is ke pt safe a n d treate d i n acc or da nce wit h pri vac y p olicies a n d dat a 
p r otecti o n a n d pri va c y la ws.  
I n acc or da nce wit h data pri vac y la ws a n d g o o d practice, eac h cli nical site s hall o btai n c o nse nt 
fr o m st u d y s u bjects t o c ollect, use a n d discl ose t heir data c o nsiste nt wit h g o o d cli nical practice 
a n d t he la ws o n c o nfi de ntialit y a n d data pri vac y re g ulati o ns.  
Me dical i nf or mati o n ma y be gi ve n t o a s u bject’s pers o nal p h ysicia n or ot her a p pr o priate 
me dical pers o n n el res p o nsi ble f or t he s u bject’s welfare, f or treat me nt p ur p os es.  
Data ge nerate d b y t his st u d y m ust be a vaila ble f or i ns pecti o n u p o n re q uest b y re prese nt ati ves 
of a p plica bl e nati o nal a n d l ocal healt h a ut h orities, s p o ns or m o nit ors, re prese ntati ves, a n d 
c olla b orat ors, a n d t h e I R B/I E C f or eac h st u d y site, as a p pr o priat e.  
All reas o na ble preca uti o ns wit hi n t he c o nstrai nts of t he a p plica ble re g ulat or y re q uire m e nt(s) 
will be ta ke n t o mai ntai n t he c o nfi de ntialit y of s u bjects' i de ntities a n d s p o ns or’s pr o prietar y 
i nf or mati o n b y a n y part y (e. g., d o mestic a n d f orei g n re g ulat or y a ut h orities, s p o ns or's 
m o nit ors, a n d a u dit ors) wit h direct access t o s u bject me dical i nf or m ati o n.  
1 1. 1. 5. 3  Miti g ati o n Me as ures i n C ase of  D at a S ec urity B re ac h  
T he data pr otecti o n officer of t he cli nical trial site s hall be i nf or me d a b o ut t he pr oject bef ore 
t he start of a cli nical st u d y. T he dat a pr ot ecti o n officer is o bli gat e d t o m o nit or c o m plia nce wit h 
t he re q uir e me nts of all d ata pr otecti o n re g ul ati o ns. T he d ata pr ot ecti o n officer m ust, t heref ore, 

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n ot o nl y be i nf or me d b ut all necess ar y i nf or m ati o n m ust be pr o vi de d s o t hat t he data pr ot ecti o n 
officer ca n f ulfill his or her i ns pecti o n o bli gati o ns.  
I n case of a data sec urit y breac h, t he data pr ot ecti o n officer s hall be i nf or me d. T he data 
pr otecti o n officer is re q uire d t o re p ort t he breac h i m me diatel y ( wit hi n 7 2 h) t o t he res p o nsi ble 
data pr otecti o n s u per vis or y a ut h orit y. S u bjects w h o are pers o nall y c o ncer ne d a n d p ote ntiall y 
e n da n gere d b y a data pr otecti o n breac h will be i nf or me d i m me diatel y. A n y p ossi ble meas ure t o 
re me d y t he d ata pr otecti o n breac h will be arra n g e d. A p pr o priate tec h nical a n d or g a nizati o nal 
meas ures are i m ple me nte d t o pr otect i nf or mati o n a n d pers o nal data pr ocesse d a gai nst 
u na ut h orize d or u nla wf ul access, discl os ure, disse mi nati o n, alterati o n, destr ucti o n, or 
acci de nt al l oss, i n partic ular w here t he pr o cessi n g i n v ol ves t he tra ns missi o n.   
1 1. 1. 6  C o m mittees Str uct ure  
1 1. 1. 6. 1  D at a M o nit ori n g C o m mittee  
T his trial will be m o nit ore d b y a n i n de pe n d e nt dat a m o nit ori n g c o m mittee ( D M C). T he 
c o m p ositi o n, r oles, res p o nsi bilities, a n d r ules g o ver ni n g t he D M C are a vaila ble i n a D M C 
C harter.  
1 1. 1. 6. 2  St u d y Steeri n g C o m mittee  
T his trial’s e xec uti o n will be s u per vise d b y a st u d y steeri n g c o m mittee ( S S C). T he 
c o m p ositi o n, r oles, res p o nsi bilities, a n d r ules g o ver ni n g t he S S C are a vaila ble i n t he S S C 
C harter.  
1 1. 1. 7  Disse mi n ati o n of Cli nic al St u d y D at a  
I n vesti gat ors a n d t heir st aff s h all h ol d c o nfi de ntial a n d n ot discl ose directl y or i n directl y t o a 
t hir d part y ot her t ha n t h ose pers o ns i n v ol ve d i n t he st u d y w h o ha ve a nee d t o k n o w, t he 
pr ot oc ol, t he data arisi n g o ut of t he st u d y, a n d a n y ot her i nf or mati o n rel ate d t o t he st u d y or t o 
S p o ns or’s pr o d ucts or res earc h pr o gra ms t hat is pr o vi de d t o t he I n vesti gat or. All s uc h pers o ns 
m ust be i nstr ucte d n ot t o f urt her disse mi nate t his i nf or mati o n t o ot hers. I n vesti gat ors s hall n ot 
use t he c o nfi de ntial i nf or mati o n f or a n y p ur p ose ot her t ha n t he st u d y. T he f ore g oi n g 
o bli gati o ns of c o nfi de nce a n d n o n -use ass u me d b y t he I n vesti gat or s hall n ot a p pl y t o (a) 
i nf or mati o n w hic h at t he ti me of discl os ure is i n t he p u blic d o mai n; ( b) i nf or mati o n w hic h 
t hereafter la wf ull y bec o mes part of t he p u blic d o mai n ot her t ha n discl os ur e b y or t hr o u g h t he 
I n vesti gat or; (c) i nf or mati o n w hic h, as e vi de nce d b y t he I n vesti gat or’s writte n rec or ds, was 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 3 2  of  1 6 9  
k n o w n b y t he I n vesti gat or pri or t o O x ular Li mite d’s discl os ure; ( d) i nf or mati o n w hic h is 
la wf ull y discl ose d t o t he I n vesti gat or b y a t hir d part y, n ot u n der a n y o bli gati o n of c o nfi de nce 
t o O x ular Li mite d; or (e) i nf or mati o n w hic h is re q uire d t o be discl ose d b y l a w or g o ver n me nt 
re g ulat or y a g e nc y, pr o vi de d reas o n a ble a d v a nce n otice of s uc h discl os ure is gi ve n t o O x ular 
Li mite d.  
All data a n d disc o veries arisi n g o ut of t he st u d y, pate nta ble or n o n -pate nta ble, s hall be t he 
s ole pr o pert y of O x ul ar Li mite d. O x ular Li mite d reser ves t he ri g ht of pri or re vie w of a n y 
p u blicati o n or prese ntati o n of i nf or mati o n relat e d t o t he st u d y. O x ular Li mite d reser ves t he 
ri g ht of pri or re vie w of a n y p u blicati o n or prese nt ati o n of i nf or mati o n relat e d t o t his st u d y. 
O x ular Li mite d ma y use t hese data n o w or i n t he f ut ure f or prese ntati o n or p u blicati o n at 
O x ular Li mite d’s discreti o n or s u b missi o n t o Re g ul at or y A ut h orities.  
1 1. 1. 8  D at a Q u alit y Ass ur a nce  
All s u bject data rel ati n g t o t he st u d y will be rec or de d o n electr o ni c C R Fs. T he i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.  
T he s p o ns or is res p o nsi ble f or t he d ata ma na g e me nt c o m plia nce of t his st u d y, i ncl u di n g 
q ualit y c hec ki n g of t he d ata, a n d ass u mes acc o u nt a bilit y f or acti o ns dele gat e d t o ot her 
i n di vi d uals. A ut h orize d re prese nt ati ves of t he s p o ns or ma y perf or m a u dits or i ns pecti o ns, 
i ncl u di n g s o urce data v erificati o n. T he p ur p os e of a n a u dit or i ns pecti o n is t o s yste maticall y 
a n d i n de pe n de ntl y e x a mi ne all st u d y -relate d acti vities a n d d oc u me nts t o det er mi ne w het her 
t hese acti vities were c o n d ucte d, a n d dat a were rec or de d, a nal yze d, a n d acc uratel y re p orte d 
acc or di n g t o t he pr ot oc ol, a n d G C P g ui deli nes of t he I C H, a n d a n y a p plica ble l ocal re g ulat or y 
re q uire me nts. T h e I n vesti gat or a grees t o acc o m m o date a n d partici pate i n a u dits c o n d ucte d at a 
reas o na bl e ti me a n d i n a reas o na bl e ma nner. T h e S p o ns or’s cli nical q ualit y ass ura nce gr o u p 
ma y re q uest a ccess t o all s o urce d oc u m e nts, e C R Fs, a n d ot her st u d y d oc u m e ntati o n f or o n -
site a u dit or i ns pecti o n.  
Direct a ccess t o t hes e d o c u me nts m ust be g uara nt ee d b y t he I n v esti gat or, w h o m ust pr o vi de 
s u p p ort at all ti mes f or t hese acti vities. A d diti o nall y, t he i n vesti gati o nal site s hall pr o vi de 
direct access t o all trial -relate d sites, s o urce data/ d oc u me nts, a n d re p orts f or t he p ur p ose of 
i ns pecti o n b y l ocal a n d re g ulat or y a ut h orities. I n t he e ve nt of t his latter, t he I n vesti gat or s hall 
c o ntact t he s p o ns or i m me diatel y if c o ntacte d b y a re g ulat or y a g e nc y a b o ut a n i ns pecti o n.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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C O N FI D E N TI A L  
Pa ge 1 3 3  of  1 6 9  
Q C pr oce d ures s hall be i m ple me nte d be gi n ni n g wit h t he data e ntr y s yste m, a n d data Q C 
c hec ks t hat will be r u n o n t he data base s h all be ge nerate d. A n y missi n g data or data a n o malies 
s hall 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 S O Ps, t he 
m o nit ors will verif y t hat t he cli nical trial is c o n d u cte d, a n d dat a are ge nerat e d, d oc u me nte 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, G C P, a n d a p plica ble re g ulat or y 
re q uire me nts. 
Cli nical st u d y rec or ds s h all be retai ne d acc or di n g t o t he f oll o wi n g re q uire me nts u nless l ocal 
re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n g er ret e nti o n peri o d t ha n s u m marize d:  
1.  
U S re g ulati o ns ( 2 1 C F R Part 3 1 2. 6 2) re q uir e t hat rec or ds a n d d oc u me nts p ertai ni n g t o 
t he c o n d uct of t his st u d y a n d t he distri b uti o n of i n vesti gati o nal pr o d ucts (i n cl u di n g 
me dical rec or ds, e C R Fs, I C Fs, test res ults, a n d i n v esti gati o nal pr o d uct rec or ds) be 
k e pt o n file b y t he I n vesti gat or f or 2 years after a mar keti n g a p plicati o n is a p pr o ve d 
f or t he i n vesti gati o nal pr o d uct f or t he i n dicati o n f or w hic h it is bei n g st u die d. If n o 
a p plicati o n is file d or a p pr o ve d, t hese rec or ds m ust be ke pt f or 2 y ears after t he  
i n vesti gati o n has bee n disc o nti n ue d a n d t he F D A has bee n n otifie d. 
2.  
I C H-G C P re q uires t hat d oc u me nts s h o ul d be retai ne d u ntil at least 2 years after t he 
last a p pr o val of a m ar keti n g a p plicati o n i n a n I C H re gi o n a n d are n o pe n di n g or 
c o nte m plate d mar k eti 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 ve 
ela pse d si nce t h e f or mal disc o nti n uati o n of cli nical de vel o p me nt of t he i n vesti gati o nal 
pr o d uct.  
N o cli nical trial rec or ds s hall be destr o ye d or tra nsferre d t o a n ot her l o cati o n or part y wit h o ut 
pri or n otificati o n a n d a ut h orizati o n fr o m t he S p o ns or.  
1 1. 1. 9  S o urce D oc u me nts  
A n i n vesti gat or is re q uire d t o pre pare a n d mai ntai n a de q uate a n d acc urate case hist ories t hat 
rec or d all o bser vati o ns a n d ot her data perti ne nt t o t he cli nical trial o n eac h s u bject e nr olle d. 
Case hist ories i ncl u de t he C R Fs a n d s u p p orti n g s o urce d oc u m e nts. S o ur ce d oc u me nts i ncl u de 
s u bject si g ne d I C Fs, a n d s u bject me dical rec or ds wit h dates a n d details of t he trial pr oce d ures 
(scree ni n g, la b orat or y a n d ot her test res ults, st u d y treat me nts, A Es, s u bject stat us, etc.). T he 
s o urce d oc u m e nts pr o vi de e vi de nce f or t h e e xiste n ce of t he s u bject a n d s u bsta ntiate t he 
i nte grit y of t he data c ollecte d. T hes e s o urce d oc u me nts s hall be file d at t he i n vesti gat or’s site. 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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C O N FI D E N TI A L  
Pa ge 1 3 4  of  1 6 9  
T he s p o ns or will pr o vi de t he st u d y sites wit h e C R Fs t hat will be c o m plete d f or eac h st u d y 
s u bject base d o n t he s o urce d oc u me nt ati o n. It is t he I n vesti gat or’s res p o nsi bilit y t o e ns ure t he 
acc urac y, c o m plete n ess, le gi bilit y, a n d ti meli ness of t he data re p ort e d i n t h e s u bject’s e C R F.  
Data re p orte d o n t he C R F or e ntere d i n t he e C R F t hat are tr a nscri be d fr o m s o urce d oc u m e nts 
s hall be c o nsiste nt wit h t he s o urce d o c u me nts or t he discre p a ncies m ust be e x plai ne d. T he 
i n vesti gat or ma y nee d t o re q uest pre vi o us me di cal rec or ds or tra nsfer rec or ds, de pe n di n g o n 
t he st u d y. Als o, c urre nt me dical rec or ds s hall be a vaila ble. 
T he I n vesti gat or, or desi g nate d re prese ntati ve, s h all c o m plete t he e C R F pa ges as s o o n as 
p ossi ble after i nf or m ati o n is c ollecte d d uri n g a n e xa mi nati o n, treat me nt, or a n y ot her cli nical 
trial pr oce d ure. A n y o utsta n di n g e ntries s hall be c o m plete d i m me diatel y after eac h s u bj ect 
c o m pletes t he cli nical tri al. A n e x pla n ati o n s hall be pr o vi de d f or all missi n g data.  
T he s p o ns or’s re pres e ntati ve will perf or m m o nit ori n g t o c o nfir m t hat data e ntere d i nt o t he 
C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifi a ble fr o m s o urce 
d oc u me nts; t hat t he safet y a n d ri g hts of s u bjects are bei n g pr otecte d; a n d t h at t he st u d y is 
bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot o c ol a n d a n y ot her st u d y 
a gree m e nts, I C H G C P, a n d all a p plica ble re g ulat or y re q uire m e nts (see Secti o n 1 1 . 1). 
1 1. 1. 1 0  St u d y a n d Site St art a n d Cl os ure  
First Act of Recr uit me nt  
T he st u d y start date is t he date o n w hic h t h e cli nical st u d y will be o pe n f or t he recr uit me nt of 
s u bjects. 
T he first act of recr uit me nt is t he first site o pe n a n d will be t he st u d y start date.  
St u d y/ Site Ter mi nati o n  
T he s p o ns or or desi g ne e reser ves t he ri g ht t o cl ose t he st u d y site or ter mi nate t he st u d y at a n y 
ti me f or a n y reas o n at t he s ole discreti o n of t he s p o ns or. St u d y sites will be cl ose d u p o n st u d y 
c o m pleti o n. A st u d y site is c o nsi dere d cl os e d w he n all re q uire d d o c u me nts a n d st u d y s u p plies 
ha ve bee n c ollecte d a n d a st u d y -site cl os ure visit has bee n perf or m e d. 
F urt her t o re g ulati o ns o utli ne d i n Secti o n 8 , reas o ns f or t he earl y cl os ure of a st u d y site b y t he 
s p o ns or or i n vesti gat or ma y i ncl u de b ut are n ot li mite d t o: 

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C O N FI D E N TI A L  
Pa ge 1 3 5  of  1 6 9  
F or st u d y ter mi nati o n:  
1.  
Disc o nti n uati o n of f urt her st u d y i nter ve nti o n de vel o p me nt . 
F or site ter mi nati o n:  
1.  
Fail ure of t he i n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uir e me nts of t he 
I R B/I E C or l ocal h ealt h a ut h orities, t he s p o ns or’s pr oce d ures, or G C P g ui deli nes 
2.  
I n a de q uat e or n o recr uit me nt (e val uate d after a reas o na ble a m o u nt of ti me) of s u bjects 
b y t he i n vesti gat or  
3.  
T otal n u m ber of s u bjects i ncl u de d earlier t ha n e x p ecte d  
If t he st u d y is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
i n vesti gat ors, t he I R B/I E Cs, t he re g ulat or y a ut h orities, a n d a n y c o ntr act res earc h 
or ga nizati o n(s) use d i n t he st u d y of t he reas o n f or t er mi nati o n or s us pe nsi o n, as s pecifie d b y 
t he a p plica ble re g ulat or y re q uire me nts. T h e i n vesti gat or s hall pr o m ptl y i nf or m t he s u bject a n d 
s hall e ns ure a p pr o priate s u bject t hera p y a n d/ or f oll o w -u p.  
1 1. 1. 1 1  P u blic ati o n P olic y  
T he data res ulti n g fr o m t his cli nical trial will be pr o prietar y i nf or mati o n of t he s p o ns or. N o ne 
of t he data res ulti n g fr o m t his cli nical trial will be all o we d t o be pres e nte d or p u blis he d i n a n y 
f or m, b y t he i n vesti gat or or a n y ot her p ers o n, wit h o ut t he pri or a p pr o val of t he s p o ns or. T he 
s p o ns or s hall n ot u nreas o na bl y ref use, or dela y p u blicati o ns base d o n t he trial . T he s p o ns or 
will p u blis h data fr o m t his cli nical trial als o i n cas e of ne gati ve res ults. 
T he s p o ns or ma y re q uest, a n d t he i n vesti gat ors s h all n ot u nreas o na bl y r ef use, t he deleti o n of 
c o nfi de ntial i nf or mati o n fr o m a pr o p ose d p u blicati o n. T he parties will use t heir best eff orts t o 
pr o vi de scie ntificall y me a ni n gf ul e q ui vale nt i nf or mati o n f or s uc h  delete d c o nfi de ntial 
i nf or mati o n. 
1 1. 2  S afet y: E ve nts, Defi niti o ns , a n d Pr oce d ures  
1 1. 2. 1  E mer ge nc y C o nt a cts f o r I n vesti g at or Re p orti n g of S afet y E ve nts  
T he pri mar y mec ha nis m f or re p orti n g a n S A E/ S A D E/ A E SI t o S p o ns or will be t he electr o nic 
data ca pt ur e s yste m ( E D C). T he site will e nter t he S A E/ S A D E/ A E SI data i nt o t he electr o nic 
s yste m as s o o n as it bec o mes a vaila ble. If t he E D C s yste m is u na vaila ble f or a peri o d of ti me 
e x pecte d n ot t o all o w re p orti n g wit hi n 2 4 h o urs, t he ( pa per) S A E/ S A D E/ A E SI f or ms will be 

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C O N FI D E N TI A L  
Pa ge 1 3 6  of  1 6 9  
se nt b y fa x t o re p ort t he e ve nt wit hi n 2 4 h o urs. C o ntacts f or S A E re p orti n g ca n be f o u n d i n 
t he I n vesti gat or Site File. 
1 1. 2. 2  A d verse E ve nts  Defi niti o n  
A d verse e ve nt mea ns a n y u nt o war d me dical o cc urre nce ass oci ate d wit h t he use of a dr u g i n 
h u ma ns, w het her or n ot c o nsi dere d dr u g -relate d. 
A n A E ca n t heref ore be a n y u nfa v ora bl e a n d u ni nt e 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 xacer bate d) te m p orall y ass ociate d wit h t he 
use of st u d y i nter ve nti o n a n d d oes n ot i m pl y a n y j u d g me nt of ca usalit y.  
A n a d vers e e ve nt ca n arise wit h a n y use of t he dr u g ( e. g., off -la bel use, us e i n c o m bi nati o n 
wit h a n ot her dr u g) a n d wit h a n y r o ute of a d mi nistrati o n, f or m ulati o n, or d ose, i ncl u di n g a n 
o ver d ose . 
1 1. 2. 3  De vice A d vers e E ve nts a n d De vice A d verse Effects  Defi niti o ns  
T he A E d efi niti o n pr o vi de d i n Secti o n 1 1. 2  i ncl u des Me dical D e vice A Es.  
I n a d diti o n, acc or di n g t o p ositi o n pa per of t he Me dical De vice C o or di nati o n Gr o u p  o n safet y 
re p orti n g f or me di cal de vices, (Me dic al De vice C o or di nati o n Gr o u p ( M D C G) 2 0 2 0 ) a n  A E is 
defi ne d as a n y u nt o war d me dical occ urre n ce, u ni nte n de d disease or i nj ur y , or a n y u nt o war d 
cli nical si g ns, i ncl u di n g a n a b n or mal la b orat or y fi n di n g, i n s u bjects, users or ot her pers o ns, i n 
t he c o nte xt of a cli nical i n vesti gati o n, w het her or n ot relate d t o t he i n vesti gati o nal de vice. 
T his defi niti o n i ncl u des e ve nts : 
a. 
t hat are a ntici p ate d as w ell as u na ntici pate d e ve nts 
b.  
occ urri n g i n t he c o nte xt of a cli nical i n vesti gati o n relate d t o t he i n vesti gati o nal de vice, 
t he c o m parat or, or t he pr oce d ures i n v ol ve d  
F or safet y re p orti n g, all acti vities relate d t o t he use of a me dical d e vice ma y be c o nsi dere d 
pr oce d ures.  
A n a d vers e de vic e effect ( A D E) is a n a d verse e ve nt relate d t o t he use of a n i n vesti gati o nal 
de vice.  
T his defi niti o n i ncl u des a n y A E res ulti n g fr o m i ns ufficie nt or i na de q uate i nstr ucti o ns f or use, 
de pl o y me nt, i m pla ntati o n, i nstallati o n, or o perati o n, or a n y malf u ncti o n of t he i n vesti gati o nal 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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C O N FI D E N TI A L  
Pa ge 1 3 7  of  1 6 9  
me dical de vice as well as a n y e ve nt r es ulti n g fr o m use err or or i nte nti o nal mis use of t he 
i n vesti gati o nal me dical de vice. 
A seri o us a d verse d e vice effect ( S A D E) is a n a d verse de vice effect t hat has res ulte d i n a n y of 
t he c o nse q ue n ce c h aracteristics of a seri o us a d v erse e ve nt (f or detaile d i nf or mati o n, refer t o 
Secti o n 1 1 . 2.8 ). 
A d e vice defi cie nc y is defi ne d as a n y i na de q uac y i n t he i de ntit y, q ualit y, d ura bilit y, relia bilit y, 
safet y, or perf or ma nce of a n i n vesti gati o nal de vice, i ncl u di n g malf u ncti o n, use err ors, or 
i na de q uac y i n t he i nf or m ati o n s u p plie d b y t he ma n ufact ur er. T he  safet y r e p orti n g of de vice  
deficie nci es f oll o ws t he g ui da nce of t hes e re g ul ati o ns as a p plica ble (E ur o pea n 
Parlia me nt/ C o u ncil ( E C) 2 0 1 7 ).  
1 1. 2. 4  Ti me Peri o d f or Detecti n g De vice Deficie ncies  
Me dical de vice defici e ncies t hat res ult i n a n i nci de nt will be detecte d a n d  d oc u me nte d d uri n g 
t he peri o d of t he st u d y i n w hic h t he me dical d e vice is use d.  
T hereafter, if  t h e i n vesti gat or lear ns of a n y de vi ce deficie nc y at a n y ti me aft er a s u bject has 
recei v e d dr u g a d mi nistrati o n wit h t he de vice , or has bee n disc har ge d fr o m t he st u d y , a n d s uc h 
a deficie n c y is c o nsi dere d reas o na bl y r elate d t o a me dical de vice pr o vi de d f or t he st u d y, t he 
i n vesti gat or will pr o m ptl y n otif y t he s p o ns or. 
1 1. 2. 5  F oll o w -u p Peri o d of De vice Defi cie ncies  
T he f oll o wi n g pri nci ples f or f oll o w -u p will be a p plie d f or de vice defici e nci es:  
1.  
F oll o w -u p a p plies t o all s u bjects, i ncl u di n g t h ose w h o disc o nti n ue st u d y i nter ve nti o n.  
2.  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat f oll o w -u p i ncl u des a n y s u p ple me ntal 
i n vesti gati o ns as i n dicate d t o el uci date t he nat ur e a n d/ or ca us alit y of t he deficie nc y. 
3.  
Ne w or u p d ate d i nf or mati o n will be rec or de d o n t he ori gi nal c o m plete d f or m wit h all 
c ha n ges si g ne d a n d date d b y t he i n vesti gat or.  
1 1. 2. 6  Re p orti n g Re q uire me nts of De vice Defici e ncies  
T he s p o ns or will re p ort  t o t he Re g ulat or y A ut h orities: 
1.  
De vice d eficie n c y -relate d S A Es a n d S A D Es, o bser ve d eit her d uri n g t he dr u g 
a d mi nistrati o n pr oce d ure or s u bse q ue ntl y re p orte d b y i n vesti gat ors (see bel o w) as 
e x pe dite d safet y re p orts f oll o wi n g t he g ui deli nes i n Secti o n 9 . 5.4 . 

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2.  
N o n -seri o us A Es d ue t o de vice deficie nci es (i ncl u di n g b ut n ot li mite d t o “fail ure t o 
treat” wit h t he de vi ce) will be re p orte d i n t he a n n u al D S U R as part of t he I N D a n n ual 
re p orti n g re q uir e me nts of 2 1 C F R 3 1 2. 3 3. 
3.  
A n y de vice d eficie n c y t hat mi g ht ha ve le d t o a seri o us a d verse e ve nt if a p pr o priate 
acti o n ha d n ot bee n t a ke n, i nter ve nti o n ha d n ot occ urre d, or circ u msta nces h a d bee n 
less f ort u nate will be re p orte d b y t he s p o ns or wit h o ut dela y t o t he c o ncer ne d 
Re g ulat or y A ut h orities.  
4.  
A n y ne w fi n di n gs t o a n y e ve nt referre d t o i n p oi nts ( 1), ( 2) a n d ( 3).  
T he f oll o wi n g re g ulati o ns a p pl y f or re p orti n g of De vice Deficie nci es t o t he S p o ns or : 
1.  
A n y d e vice d eficie n cies will be re p orte d t o t he s p o ns or wit hi n 2 4 h o urs aft er t he 
i n vesti gat or deter mi nes t hat t he e ve nt meets t he pr ot oc ol defi niti o n of a me dical 
de vice deficie nc y.  
2.  
T he me dical de vi ce deficie nc y  wit h o ut a n y relat e d A E or relat e d t o n o n -seri o us A E 
will be rec or de d i n t he c orres p o n di n g E D C c h a pters . T he i n vesti gat or has t o n otif y t he 
S p o ns or a b o ut a ne wl y rec or de d me dical de vice deficie nc y  via e mail or a tel e p h o ne 
call. T he me dical de vice deficie nci es relat e d t o S A Es, S A D Es a n d A E SIs will be 
rec or de d i n t he E D C bas e d S A E f or m. If t h e E D C is u na vaila ble, t he n t he pr oce d ure 
descri be d i n  Secti o n 1 1. 2. 1  m ust be a p plie d . 
3.  
T he s p o ns or will be t he c o ntact f or t he recei pt of de vice deficie nc y re p orts.  
T he i n vesti gat or will pr o m ptl y re p ort all S A Es or A Es s us pecte d t o be d e vice defi cie nc y -
relate d occ urri n g p ost -tr eat me nt wit h a n y me dical de vice pr o vi de d f or use i n t he st u d y f or t he 
s p o ns or t o f ulfill t he le gal res p o nsi bilit y t o n otif y a p pr o priate re g ulat or y a ut h orities a n d ot her 
e ntities a b o ut certai n safet y i nf or mati o n relati n g t o me dical de vices b ei n g use d i n cli nical 
stu dies.  
T he i n vesti gat or, or res p o nsi ble pers o n acc or di n g t o l ocal re q uire m e nts, will c o m pl y wit h t he 
a p plica ble l ocal re g ulat or y re q uire me nts relati n g t o t he re p orti n g of S A Es or S A D Es 
deter mi ne d t o be de vi ce deficie nc y -rel ate d t o t he I R B/I E C. 
 
1 1. 2. 7  Re g ul at or y Re p orti n g Re q uire me nts (Seri o us S afet y E ve nts , S afet y Re p orti n g i n 
Cli nic al I n vesti g ati o ns of Me dic al D e vices , a n d D S U R).   

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T he s p o ns or has a l e gal r es p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a g e ncies (as a p plica ble) a b o ut t he s afet y of a st u d y treat me nt u n der cli nical 
i n vesti gati o n. T he s p o ns or will c o m pl y wit h c o u ntr y -s pecific re g ulat or y re q uire me nts relate d 
t o safet y re p orti n g t o t he re g ulat or y a ut h orit y, I R Bs/I E Cs, a n d i n vesti gat ors acc or di n g t o t he 
re g ulati o ns liste d i n Secti o n 1 1 . 2. T he s pecific re p orta bilit y criteria, re p orti n g ti meli nes a n d 
pr oce d ures f or e x pe dite d re p orti n g, cr oss -re p orti n g f or t he i n vesti gati o nal me dici nal pr o d uct 
a n d me dical de vice , a n d s u b missi o n of t he Dr u g Safet y U p dat e Re p ort ( D S U R) will be 
o utli ne d i n t he Safet y Ma na ge me nt Pla n a n d i n acc or da nce wit h  t he re g ulati o ns liste d i n t he 
Secti o n 1 1 . 2. 
1 1. 2. 8  Seri o us A d verse E ve nt  Defi niti o n  
A n S A E is defi ne d as a n y u nt o war d me dical o cc urre nce t hat, at a n y d os e, meets o ne or m ore 
of t he criteri a liste d:  
1.  
Res ults i n de at h  
2.  
Is life-t hre ate ni n g 
T he ter m life -t hr eate ni n g i n t he defi niti o n of seri o us refers t o a n e ve nt i n w hic h t he 
s u bject was at (i m me diat e) ris k of deat h at t he ti me of t he e v e nt. It d oes n ot refer t o a n 
e ve nt, w hic h h y p ot heticall y mi g ht ha ve ca use d deat h if it were m or e se vere.  
3.  
Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n  
I n ge neral, h os pitalizati o n si g nifies t hat t he s u bject has bee n a d mitte d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) t o t he h os pital or e mer g e nc y war d f or o bser vati o n 
a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h ysicia n’s office or 
o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A Es. If a 
c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he e ve nt is 
seri o us. W he n i n d o u bt as t o w het her h os pitalizati o n occ urre d or was necessar y, t he 
A E  s h o ul d be c o nsi dere d seri o us. 
H os pitalizati o n f or ele cti ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot w orse n 
fr o m baseli ne is n ot c o nsi dere d a n A E. 
4.  
Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y  

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T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct 
n or mal life f u ncti o ns.  
T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie n ces of relati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea dac he, n a usea, v o miti n g, diarr hea, i nfl ue nza, 
a n d acci de ntal tra u ma ( e.g ., s prai ne d a n kle) t hat ma y i nterfere wit h or pre ve nt 
e ver y da y life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.  
5.  
Is a c o n ge nit al a n o m al y/ birt h defect 
6.  
Ot her i m p ort a nt me dic al e ve nts:  
Me dical or scie ntifi c j u d g me nt s h o ul d be e xercise d b y t he i n vesti gat or i n deci di n g 
w het her S A E re p orti n g is a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical 
e ve nts t hat ma y n ot be i m me diatel y life -t hreate ni n g or res ult i n deat h or 
h os pitalizati o n b ut ma y je o par dize t he s u bject or ma y re q uire m e dical or s ur gical 
i nter ve nti o n t o pre ve nt o ne of t he ot her o ut c o mes liste d i n t he a b o ve defi niti o n. T hese 
e ve nts s h o ul d us uall y be c o nsi dere d seri o us.  
E xa m ples of s uc h e v e nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt i n 
a n e mer g e nc y r o o m or at h o me f or aller gic br o n c h os pas m, bl o o d d yscrasias, 
c o n v ulsi o ns n ot res ulti n g i n h os pitalizati o n, or de vel o p me nt of i nter ve nti o n 
de pe n de n c y or i nter v e nti o n a b use.   
1 1. 2. 9   S us pecte d U ne x pecte d Seri o us A d verse Re acti o n  Defi niti o n  
F or a n e ve nt t o be q ualifi e d as a s us pe cte d u ne x p ecte d seri o us a d v erse reacti o n ( S U S A R), t he 
A E m ust meet t hree ( 3) criteria:  
•  t he e ve nt is seri o us,  
•  t here is a reas o na bl e p ossi bilit y f or t he e ve nt t o esta blis h a ca usal r elati o ns hi p t o t he 
st u d y dr u g bei n g researc he d (i.e., it q ualifies a d v erse reacti o n), a n d  
•  t he nat ure a n d s e verit y of t he reacti o n are n ot i n a gree me nt wit h t he pr o d u ct 
i nf or mati o n a n d t he safet y i nf or mati o n i n t he I B (i.e., t he reacti o n is u ne x pecte d as per 
t he refere n ce safet y i nf or mati o n, i.e., t he e ve nt is u ne x pecte d). 
All S U S A Rs will be re p orte d as re q uire d t o t he C o m pete nt A ut h orities a n d t he Et hics 
C o m mittee ( E C)/I nstit uti o nal Re vie w B oar ds (I R Bs)  as re q uire d b y a p plica ble re g ulati o ns . 

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A n  a d vers e e ve nt or s us pecte d a d v erse reacti o n is c o nsi dere d “ u ne x pecte d” if it is n ot liste d i n 
or n ot liste d at t he s pecifi cit y or se verit y t hat has b ee n o bser ve d i n t he I B’s  Refere n ce Safet y 
I nf or mati o n f or t he i n v esti gati o nal me dici nal pr o d uct a n d/ or i n vesti gati o nal de vice.  
F or t he c o m parat or Oz ur de x ® , t he R SI fr o m t he U S Prescri bi n g I nf or mati o n will be use d. 
I n vesti gat or g ui da nce f or re p orti n g of Oz ur de x ® e ve nts is still pr o vi de d i n t he I n vesti gat or 
Br oc h ure.  
" U ne x pecte d," as use d i n t his defi niti o n, als o refers t o a d verse e ve nts or s us pecte d a d v erse 
reacti o ns t hat are me nti o ne d i n t he I B as occ urri n g wit h a class of dr u gs or as a ntici pate d fr o m 
t he p har mac ol o gical pr o p erties of t he dr u g b ut are n ot s pecificall y me nti o ne d as occ urri n g 
wit h t he partic ular dr u g u n der i n vesti gati o n.  
1 1. 2. 1 0  De vice Seri o us A d verse E ve nt, Seri o us A d verse De vice Effect, a n d U ne x pecte d 
Seri o us A d verse D e vice Effect  Defi niti o ns  
To all o w f or c o m para bilit y of safet y r e p orti n g acr oss trials i n t he de vel o p me nt pr o gra m of 
O x ular o n t he O x ul u mis de vice, als o a cate g orizati o n of De vice S A Es f oll o wi n g t he me dical 
de vice re g ulati o ns o utli ne d i n t he Secti o n 1 1. 2. 1 1  will be perf or me d . T he criteria f or 
seri o us ness assess me nt f or t he Me dical D e vice A d verse E ve nt are sli g htl y differe nt fr o m t he 
S A E criteria o utli ne d i n Secti o n 1 1 . 2. 8. 
A De vice S A E  is a n a d v erse e ve nt t hat le d t o  
1.  
D e at h  
2.  
S eri o us deteri or ati o n i n t he he alt h of t he s u bject, t h at eit her res ulte d i n:  
•  
Life -t hreate ni n g ill ness or i nj ur y. 
•  
Per ma ne nt i m pair me nt of a b o d y str uct ure or a b o d y f u ncti o n.  
•  
H os pitalizati o n or pr ol o n ge d h os pitalizati o n. Pla n ne d h os pitalizati o n f or a pre -
e xisti n g c o n diti o n, or a pr oce d ure re q uire d b y t he pr ot oc ol, wit h o ut seri o us 
deteri orati o n i n he alt h, is n ot c o nsi dere d a n S A E.  
•  
Me dical or s ur gic al i nter ve nti o n t o pre ve nt life -t hreate ni n g ill ness or i nj ur y or 
per ma ne nt i m pair me nt t o a b o d y str uct ure or a b o d y f u ncti o n.  
•  
C hr o nic disease ( as per M D R 2 0 1 7/ 7 4 5).  
3.  
F et al distress, f et al de at h, or a c o n ge nit al a b n or m alit y or birt h defect  

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A seri o us a d verse d e vice effect ( S A D E) is defi ne d as a n a d verse de vi ce effect t hat has 
res ulte d i n a n y of t he c o nse q ue nces c haracteristic of a n S A E. 
F or t he re p orta bilit y assess me nt p ur p oses t he f oll o wi n g e ve nts are als o disc usse d i n t his 
secti o n base d o n t he re g ulat or y g ui deli nes liste d i n t he Secti o n 1 1. 2. 1 1 , s hall be re p orte d, 
wit h o ut dela y t o c orres p o n di n g a ut h orities  as per l ocal re g ulati o ns:  
a)  a n y seri o us a d v erse e ve nt t hat has a ca us al relati o ns hi p wit h t he i n vesti gati o nal de vice, 
t he c o m parat or, or t he i n vesti gati o n pr oce d ure or  w here s u c h ca us al relati o ns hi p is 
reas o na bl y p ossi ble; 
b)  a n y de vice d eficie n c y t hat mi g ht ha ve le d t o a seri o us a d verse e ve nt if a p pr o priate 
acti o n ha d n ot bee n t a ke n, t he i nter ve nti o n ha d n ot occ urre d, or circ u msta nces ha d 
bee n less f ort u n ate;  
c)  a n y ne w fi n di n gs i n relati o n t o a n y e ve nt referre d t o i n p oi nts a) a n d b).  
A n u ne x pect e d seri o us a d verse de vi ce effect U S A D E (als o i de ntifie d as U A D E i n U S 
Re g ulati o ns 2 1 C F R 8 1 3. 3), is defi ne d as a seri o us a d verse d e vice effect t hat b y its nat ure, 
i nci de nce, se v erit y, or o utc o me has n ot bee n i de ntifie d i n t he c urre nt versi o n of t he ris k 
a nal ysis re p ort f or t he de vice.  
1 1. 2. 1 1  Rec or di n g a n d F oll o w -U p of A d vers e E ve nts a n d/ or Seri o us A d verse E ve nts 
( Dr u g or De vice)  
W he n a n A E/ S A E occ urs, it is t he res p o nsi bilit y of t he i n vesti gat or t o re vie w all 
d oc u me ntati o n ( e. g., h os pital pr o gress n otes, la b orat or y re p orts, a n d dia g n ostics re p orts) 
relate d t o t he e v e nt. T he i n vesti gat or will t he n rec or d all rele va nt A E/ S A E i nf or mati o n. 
It is n ot  acce pta bl e f or t h e i n vesti gat or t o se n d p h ot oc o pies/ di gital c o pies of t he s u bject’s 
me dical rec or ds t o O x ular Lt d. or its dele gates i n st ea d of c o m pleti n g  t he S A E re p ort f or m. 
T here ma y b e i nsta nces w he n c o pies of m e dical r ec or ds f or certai n cas es are re q u este d b y 
O x ular Lt d or its dele gat es. I n t his case, all s u bject i de ntifiers, e xce pt f or t h e s u bject n u m ber, 
m ust be re dact e d o n t he c o pies of t he me dical r ec or ds bef ore s hari n g  wit h O x ular Lt d. or its 
dele gates.  
T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, 
a n d/ or ot her cli nic al i nf or mati o n. W he ne v er p ossi ble, t he dia g n osis ( n ot t he i n di vi d ual 
si g ns/s y m pt o ms) will be d oc u me nte d as t he A E/ S A E. 

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I n vesti gat ors s h o ul d use c orrect me dical ter mi n ol o g y/c o nce pts w he n rec or di n g A Es or S A Es 
o n t he e C R F a n d/ or S A E f or m. C oll o q uialis ms a n d a b bre viati o ns s h o ul d be a v oi de d. Seri o us 
A Es m ust als o be rec or de d o n t he A E e C R F. O nl y 1  me dical c o nce pt s h o ul d be rec or de d i n 
t he e ve nt fiel d o n t he A E e C R F a n d S A E f or m (if a p plica ble). 
A d verse E ve nts Occ urri n g Sec o n d ar y t o Ot her E ve nts  
I n ge neral, A Es o cc urri n g sec o n dar y t o ot her e ve nts (e.g ., casca de e ve nts or cli nical se q uelae) 
s h o ul d als o be e ntere d as se parat e A Es. F or e xa m ple, if se vere diarr hea is k n o w n t o ha ve 
res ulte d i n de h y drati o n, b ot h diarr hea a n d de h y drati o n s h o ul d be e ntere d as A Es o n t he e C R F, 
a n d if als o seri o us, o n t he S A E f or m .  
Persiste nt or Rec urre nt A d verse E ve nts  
A persiste nt A E e xte n ds c o nti n u o usl y, wit h o ut res ol uti o n bet wee n s u bject e val uati o n ti me 
p oi nts. S uc h e ve nts s h o ul d o nl y be rec or de d o nce i n t he e C R F u nless t heir se verit y i ncreases. 
If a persiste nt A E bec o m es m ore se vere or its si g n or s y m pt o ms occ ur m ore fre q ue ntl y, t he 
c ha n ge i n t he se v erit y gr a di n g, t he date w h e n t he se verit y c ha n g e was re p orte d, a n d a n y n e w 
acti o n ta ke n s hall be rec or de d i n t he e C R F. 
A rec urre nt A E o cc urs a n d res ol ves bet w ee n s u bject e val uati o n ti me p oi nts a n d s u bse q ue ntl y 
rec urs. All rec urre nt A Es s h o ul d be rec or de d i n di vi d uall y o n t he A E e C R F. 
A b n or m al L a b or at or y Val ues  
O nl y cli nicall y si g nifica nt la b orat or y a b n or m alities will be rec or de d as A Es o n t he e C R F a n d 
S A E f or m (if a p plica bl e).  
If t he la b orat or y a b n or m alit y ca n be c h aracterize d b y a precis e cli nical ter m, t he cli nical ter m 
s h o ul d be rec or de d as t he A E or S A E. F or e x a m ple, a n ele vate d ser u m p otassi u m le vel of 
7. 0  m E q/ L s h o ul d be rec or de d as “ h y p er kal e mia”.  
O bser vati o ns of t he s a me cli nicall y si g nifica nt la b orat or y a b n or m alit y fr o m visit t o visit 
s h o ul d n ot be re peat e dl y rec or de d as A Es o n t he e C R F a n d S A E f or m (if a p plica ble), u nless 
t heir se verit y, seri o us ness, or eti ol o g y c ha n ges.  
 
 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 4 4  of  1 6 9  
De at hs  
All deat hs t hat occ ur d uri n g t he pr ot oc ol -s pecifie d A E re p orti n g peri o d (see Secti o n  9 . 5. 1), 
re gar dl ess of attri b uti o n, will be rec or de d o n t he A E e C R F a n d S A E f or m a n d re p orte d t o t he 
S p o ns or wit hi n 2 4  h o urs of e ve nt k n o wle d ge.  
W he n rec or di n g a d eat h, t he e ve nt or c o n diti o n t hat ca use d or c o ntri b ute d t o t he fatal o utc o me 
s h o ul d be rec or de d as a si n gle me dical c o nce pt. F or e xa m ple, if d eat h res ulte d fr o m 
res pirat or y fail ure, t he A E rec or de d s h o ul d be “ R es pirat or y Fail ure”, a n d t he o utc o me of t he 
A E w o ul d be “ D eat h”. If t he ca use of deat h is u n k n o w n a n d ca n n ot b e ascertai ne d at t he ti me 
of re p orti n g, r ec or d “ u ne x plai ne d deat h” o n t h e A E e C R F a n d S A E f or m.  
Pree xisti n g Me dic al C o n diti o ns  
A pree xisti n g me dical c o n diti o n is o ne t hat ha d bee n alrea d y  pres e nt at t he start of t he st u d y  
(at t he ti me of t he si g nat ure of t he I C F). S uc h c o n diti o ns s h o ul d be rec or de d o n t he Me dical 
a n d S ur gical Hist or y e C R F  (see als o Secti o n 1 1. 1. 9 ). 
A pre -e xisti n g me dical c o n diti o n s h o ul d be rec or de d as a n A E or S A E o nl y  if t he fre q u e nc y, 
se verit y, or c haracter of t he c o n diti o n w orse ns d uri n g t he st u d y. W he n rec or di n g s uc h e ve nts 
o n a n A E e C R F a n d S A E f or m (if a p plica ble), it is i m p orta nt t o c o n ve y t he c o nce pt t hat t he 
pree xisti n g c o n diti o n has c ha n ge d b y i ncl u di n g a p plic a ble descri pt ors ( e.g ., “ m ore fre q ue nt 
hea dac hes”).  
H os pit aliz ati o n, Pr ol o n ge d H os pit aliz ati o n , or S ur ger y  
A n y A E t hat res ults i n h os pitalizati o n or pr ol o n ge d h os pitalizati o n s h o ul d be d oc u me nte d a n d 
re p orte d as a n S A E u nless s pecificall y i nstr ucte d ot her wise i n t he pr ot oc ol.  
S peci al Sit u ati o ns Re p orti n g  
Me dicati o n err ors a n d us es o utsi de w hat is f ores ee n i n t he pr ot oc ol, i ncl u di n g o ver d ose a n d 
occ u pati o nal e x p os ure m ust be re p orte d t o t he S p o ns or o n a n A E e C R F a n d a n S A E f or m f or 
trac ki n g p ur p oses a n d will be c o nsi dere d a pr ot oc ol de viati o n. A d diti o nal i nstr ucti o ns 
f or re p orti n g s pecial sit uati o n i nf or mati o n will be pr o vi de d b y t he S p o ns or at t he ti me of 
n otificati o n.  
 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 4 5  of  1 6 9  
Assess me nt of I nte nsit y  
T he i n vesti gat or will assess t he i nte nsit y f or eac h A E a n d S A E re p orte d d uri n g t he st u d y a n d 
assi g n it t o o ne of t he f oll o wi n g cate g ories:  
1.  
Mil d:  
A t y pe of a d v erse e ve nt t hat is us uall y tra nsie nt a n d ma y re q uire o nl y mi ni mal 
treat me nt or t hera pe utic i nter ve nti o n. T he e v e nt d oes n ot ge nerall y i nterfere wit h t he 
us ual acti vities of dail y li vi n g.  
2.  
M o derate:  
A t y pe of a d v erse e ve nt t hat is us uall y alle viate d wit h a d diti o nal s pecific t hera pe utic 
i nter ve nti o n. T he e v e nt i nterferes wit h us ual acti vities of dail y li vi n g, ca usi n g 
disc o mf ort b ut p oses n o si g nifica nt or per ma n e nt ris k of har m t o t he researc h s u bject.  
3.  
Se vere:  
A t y pe of a d v erse e ve nt t hat i nterr u pts us ual acti vities of dail y li vi n g si g nifica ntl y 
affects cli nical stat us or ma y re q uire i nte nsi ve t h era pe utic i nter ve nti o n.  
Assess me nt of C a us alit y  
1.  
T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y i nter ve nti o n a n d 
eac h o cc urre nce of eac h A E/ S A E/ de vice defi cie nc y. T he i n vesti gat or will use cli nical 
j u d g me nt t o deter mi ne t he relati o ns hi p. 
2.  
T he relati o ns hi p will be deter mi ne d b y t he I n v esti gat or acc or di n g t o t he f oll o wi n g 
criteria (M e dical D e vice C o or di nati o n Gr o u p ( M D C G) 2 0 2 0 ): 
1.  
N ot rel at e d : T he rel ati o ns hi p t o t he i nter ve nti o n ca n be e x cl u de d. 
2.  
P ossi bl y rel ate d : T he rel ati o ns hi p wit h t he i nter ve nti o n is wea k b ut ca n n ot be 
r ule d o ut c o m pletel y. Alter nati ve ca uses are als o p ossi ble. 
3.  
Pr o b a bl y rel ate d : T he relati o ns hi p wit h t he i nter ve nti o n see ms rele va nt a n d/ or 
t he e ve nt c a n n ot reas o n a bl y be e x plai ne d b y a n ot her ca us e. 
4.  
C a us all y rel ate d : T he seri o us e ve nt is ass ociate d wit h t he i nter ve nti o n be y o n d 
reas o na bl e d o u bt. 
Assess me nt of t he O utc o me of A d verse E v e nts  
T he I n vesti gat or will rec or d t he o utc o me of A Es a n d S A Es usi n g t he f oll o wi n g 
criteria:  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 4 6  of  1 6 9  
Rec o vere d/res ol ve d:  T h e s u bject has f ull y rec o vere d fr o m t he e ve nt, wit h n o resi d ual 
effects o bser va ble.  
Rec o vere d/res ol ve d wit h se q uel ae:  T he s u bject has rec o v ere d fr o m t he e ve nt, b ut 
wit h resi d ual se q uela e effects o bser va bl e.  
N ot rec o vere d/res ol ve d:  Effects of t he e v e nt are still prese nt.  
Rec o veri n g/res ol vi n g:  T he s u bject has i m pr o ve d b ut has n ot f ull y rec o vere d fr o m t he 
e ve nt.  
F at al:  T he d eat h is relate d t o t he e ve nt.  
U n k n o w n:  T he o utc o me of t he e ve nt is u n k n o w n t o t he re p orter ( e.g ., t h e s u bject was 
l ost t o f oll o w-u p).  
F oll o w -u p of A Es a n d S A Es  
T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d u ct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as me dicall y i n dicate d or as re q uest e d b y t he s p o ns or or 
s p o ns or’s desi g nee t o el uci date t he nat ur e a n d/ or ca usalit y of t he A E or S A E as f ul l y as 
p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y t ests or i n vesti gati o ns, hist o pat h ol o gical 
e xa mi nati o ns, or c o ns ultati o n wit h ot her healt h care pr ofessi o nals.   
S A Es u nrelate d t o st u d y treat me nt a n d n o n -seri o us A Es are t o be f oll o we d u ntil t he last 
sc he d ule d st u d y visit ( E O S visit), wit h t he o utc o me at t hat p oi nt of ti me t o be rec or de d i n t he 
e C R F. S A Es relate d t o st u d y treat me nt are t o be f oll o we d u p u ntil res ol u ti o n or u ntil t he y 
ret ur n t o baseli ne, sta bili ze, or t he s u bject is l ost t o f oll o w-u p. Res ol uti o n of A Es a n d S A Es 
( wit h dates) s h o ul d be d o c u me nte d o n t he A E e C R F a n d S A E f or m (if a p pli ca ble) a n d i n t he 
s u bject’s me dical rec or d t o facilitate s o urce data verificati o n. F or s o me S A Es, t he S p o ns or or 
its desi g nee ma y f oll o w u p b y tele p h o ne, facsi mile, electr o ni c mail, a n d/ or a m o nit ori n g visit 
t o o btai n a d diti o nal case details dee me d necessar y t o a p pr o priatel y e v al uate t he S A E re p ort 
(e. g., h os pital disc har g e s u m mar y, c o ns ulta nt re p ort, or a ut o ps y re p ort).  
If a s u bject dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d f oll o w-u p peri o d, t he 
i n vesti gat or will pr o vi de t he s p o ns or or s p o ns or’s desi g nee wit h a c o p y of a n y p ost m orte m 
fi n di n gs i ncl u di n g hist o pat h ol o g y. 
 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 4 7  of  1 6 9  
E mer ge nc y u n m as ki n g pr oce d ure  
I n t he e ve nt of a me dical e mer ge n c y, w he n k n o wle d ge of treat me nt assi g n me nt is nee de d f or 
i m me diate me dical ma na ge me nt of t he s u bject’s h ealt h, I n vesti gat ors ca n o btai n u n mas ke d 
treat me nt assi g n me nts t hr o u g h t he ce ntr alize d ra n d o mizati o n s yste m at a n y ti me. T h or o u g h 
d oc u me ntati o n of t he rati o nale f or u n mas ki n g is re q uire d. C o ns ultati o n of t he S p o ns or 
Me dical M o nit or is rec o m me n de d f or all u n mas ki n g re q uests.  
  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 4 8  of  1 6 9  
1 2  O utc o me Assess me nts a n d Q uesti o n n aires  
1 2. 1  S u bject’s E x perie nce Assess me nt –  Visit 2 , D a y 0 
 
S u bject’s E x perie nce Assess me nt:  
C urre nt a n d Pr oce d ure P ai n & Dis c o mf ort  
To be c o m plete d b y t he Site I nter vie wer  
Site N u m ber  
 
S u bject n u m ber  
 
Date  
 
Visit n u m ber  
Visit 2 , Da y 0 
I nter vie w er / c o m plete d b y ( pri nt 
na me)  
 
I nstr ucti o ns f or t he site i nter vie wer: 
I nstr uct s u bjects o nl y t o a ns wer t he q uesti o ns o n pr oce d ur al p ai n a n d disc o mf ort. T his 
is of gre at i m p ort a nce s pecific all y i n P art B) t o a v oi d s h ari n g of a n y p ote nti all y 
u n m as ki n g i nf or m ati o n b y t he s u bject.  
As k t he st u d y s u bject t he q uesti o ns bel o w after t h e p ost -pr oce d ure o bs er vati o n peri o d.  
Q uesti o ns s h o ul d be as ke d at a n y ti me after 6 0 mi n utes p ost -treat me nt b ut s h o ul d n ot be as ke d 
wit hi n  fi ve mi n utes fr o m t he c o m pleti o n of a n y p ost-treat me nt meas ure me nt (e. g., O C T, I O P, 
etc.). I n dic ate t he st u d y s u bject’s res p o ns e b y c hec ki n g o ne  res p o ns e f or eac h q uesti o n. 
I nstr u cti o ns f or t he s u bject (t o be rea d t o t he s u bject b y t he i nter vie wer): Please a ns wer t he 
f oll o wi n g q uesti o ns a b o ut y o ur e x perie n ce of t h e pr oce d ure.  
 
Q uesti o n 1:  Are y o u c urre ntl y  e x perie n ci n g pai n  i n t he pr oce d ure e y e?  
☐ Yes  
☐ N o  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 4 9  of  1 6 9  
Q uesti o n  2: Rate y o ur c u rre nt  le vel of pai n  i n y o ur pr oce d ure e y e o n a s cal e of 1 –  5  
☐ ( 1) N o Pai n 
☐ ( 2) Mi ni mal Pai n 
☐ ( 3) Mil d Pai n 
☐ ( 4) M o derate Pai n 
☐ ( 5) Se vere Pai n 
Q uesti o n  3:  Rate y o ur pai n d uri n g  t he pr oce d ure  o n a scale of 1 –  5  
☐ ( 1) N o Pai n 
☐ ( 2) Mi ni mal Pai n 
☐ ( 3) Mil d Pai n 
☐ ( 4) M o derate Pai n 
☐ ( 5) Se vere Pai n 
Q uesti o n  4  Rate y o ur pai n after c o m pleti o n , of t h e pr oce d ure  o n a scale of 1 –  5  
☐ ( 1) N o Pai n 
☐ ( 2) Mi ni mal Pai n 
☐ ( 3) Mil d Pai n 
☐ ( 4) M o derate Pai n 
☐ ( 5) Se vere Pai n 
Q uesti o n  5 : Are y o u c urre ntl y  e x perie n ci n g disc o mf ort  i n t he pr oce d ure e y e?  
☐ Yes  
☐ N o  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 5 0  of  1 6 9  
Q uesti o n  6 : Rate y o ur c u rre nt  le vel of disc o mf ort  i n y o ur pr oce d ure e y e o n a scale of 1 –  5  
☐ ( 1) N o Disc o mf ort 
☐ ( 2) Mi ni mal Disc o mf ort 
☐ ( 3) Mil d Disc o mf ort 
☐ ( 4) M o derate Disc o mf ort 
☐ ( 5) Se vere Disc o mf ort 
Q uesti o n  7 : Rate y o ur disc o mf ort  d uri n g  t he pr oce d ure  o n a s cale of 1 –  5  
☐ ( 1) N o Disc o mf ort 
☐ ( 2) Mi ni mal Disc o mf ort 
☐ ( 3) Mil d Disc o mf ort 
☐ ( 4) M o derate Disc o mf ort 
☐ ( 5) Se vere Disc o mf ort 
Q uesti o n  8 : Rate y o ur disc o mf ort  after c o m pleti o n , of t he pr oce d ure  o n a scale of 1 –  5  
☐ ( 1) N o Disc o mf ort 
☐ ( 2) Mi ni mal Disc o mf ort 
☐ ( 3) Mil d Disc o mf ort 
☐ ( 4) M o derate Disc o mf ort 
☐ ( 5) Se vere Disc o mf ort 
Si g nat ure of site -
i nter vie wer 
 
Date  
 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 5 1  of  1 6 9  
1 2. 2  S u bject’s E x perie nce Assess me nt –  D a y 1, Visit 3 t hr o u g h Wee k 4, Visit 5  
S u bject’s E x perie nce Assess me nt:  
C urre nt a n d Pr oce d ure P ai n & Dis c o mf ort  
To be c o m plete d b y t he Site I nter vie wer  
Site N u m ber  
 
S u bject n u m ber  
 
Date  
 
Visit n u m ber (circle o n e)  
☐ Da y 1 ( Visit 3)  
☐ Da y 7 ( Visit 4)  
☐ Da y 3 0 ( Visit 5)  
I nter vie w er / c o m plete d b y ( pri nt na me) 
 
I nstr ucti o ns f or site i nter vie wer: 
I nstr uct s u bjects o nl y t o a ns wer t he q uesti o ns o n pr oce d ur al p ai n a n d disc o mf ort. T his 
is of gre at i m p ort a nce s pecific all y i n P art B) t o a v oi d s h ari n g of a n y p ote nti all y 
u n m as ki n g i nf or m ati o n b y t he s u bject.  
As k t he st u d y s u bject t he q uesti o ns bel o w. Q uesti o ns ca n be as k e d at a n y ti me d uri n g t he 
st u d y visit a n d se parate d b y at least fi ve mi n utes fr o m t he c o m pleti o n of a n y p ost -treat me nt 
meas ure me nt ( e. g., O C T, I O P, etc.). I n di cate t he st u d y s u bject’s res p o nse b y c hec ki n g o ne 
res p o nse f or eac h q uesti o n. 
I nstr u cti o ns f or st u d y s u bject (t o be rea d t o t he s u bject b y t he i nter vie wer): Please a ns wer t he 
f oll o wi n g q uesti o ns a b o ut y o ur c urre nt le v el of pai n a n d disc o mf ort i n t he e ye w hic h recei ve d 
t he st u d y treat me nt.  
Q uesti o n  1:  Are y o u c urre ntl y  e x perie n ci n g pai n  i n t he pr oce d ure e y e?  
☐ Yes  
☐ N o  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 5 2  of  1 6 9  
Q uesti o n  2: Rate y o ur c u rre nt  le vel of pai n  i n y o ur pr oce d ure e y e o n a s cal e of 1 –  5  
☐ ( 1) N o Pai n 
☐ ( 2) Mi ni mal Pai n 
☐ ( 3) Mil d Pai n 
☐ ( 4) M o derate Pai n 
☐ ( 5) Se vere Pai n 
Q uesti o n  3:  Are y o u c urre ntl y  e x perie nci n g disc o mf ort  i n t he pr oce d ure e ye?  
☐ Yes  
☐ N o  
Q uesti o n  4:  Rate y o ur c u rre nt  le vel of disc o mf ort  i n y o ur pr oce d ure e y e o n a scale of 1 –  5  
☐ ( 1) N o Disc o mf ort 
☐ ( 2) Mi ni mal Disc o mf ort 
☐ ( 3) Mil d Disc o mf ort 
☐ ( 4) M o derate Disc o mf ort 
☐ ( 5) Se vere Disc o mf ort 
 
Si g nat ure of site -
i nter vie wer 
 
Date  
 
 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 5 3  of  1 6 9  
1 2. 3  Reti n al P h ysici a n’s Assess me nt of t he A d mi nist r ati o n Pr oce d ure  
Reti n al p h ysici a n’s d oc u me nt ati o n a n d  
Assess me nt of t he Tre at me nt A d mi nistr ati o n Pr oce d ure  
T his q uesti o n naire s h o ul d be c o m plete d b y t h e tr eati n g p h ysicia n  ( u n mas ke d i n vesti gat or i n 
Part B) f or all s u bjects, re gar dless of treat me nt assi g n me nt. F or s u bjects assi g ne d t o Oz ur de x 
i n Part B, o nl y q uesti o ns u n der  1 . a n d 2. are a p plica ble. T h e re mai ni n g q uesti o ns are relate d t o 
t he O X U -0 0 1 a d mi nistrati o n pr oce d ure usi n g t he O x ul u mis ®  de vice  a n d t h eref ore d o n ot h a ve 
t o be c o m plete d f or s u bjects assi g ne d t o Oz ur de x. 
If t he O x ul u mis®  pr oce d ure is re p eate d , i. e., if t he O X U-0 0 1  a d mi nistrati o n pr oce d ure is 
perf or me d  o n t w o treat me nt da ys or i n 2 se parate sessi o ns o n o ne da y, t he q uesti o n naire will 
nee d t o be c o m plete d t wice.  If t he vari a nt w o ul d be s witc he d wit hi n o ne treat me nt sessi o n ( e. g., 
i n a n o perati n g r o o m wit h a first n o n-c o m plete d O X U -0 0 1 Sta n dar d  pr oce d ural varia nt directl y 
f oll o we d b y a n O X U-0 0 1 C o njI ncisi o n  Pr oce d ural V aria nt, o nl y o ne assess me nt nee ds t o be 
c o m plete d.  
I ntr o d ucti o n:  
N ote t hat a n y diffi c ult y or c halle n ge wit h t he de vi ce n ote d bel o w m a y q ualif y as a n a d v erse 
e ve nt ( A E) or as a n a d verse de vic e effect ( A D E) a n d nee ds t o be rec or de d as s uc h i n t he st u d y 
d oc u me ntati o n (s o urce a n d C R F).  
 
D ate of Assess m e nt:  _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _( d d/ m m m/ y y y y)  
Setti n g:  
Pr oce d ural Varia nt  
 Cli nic  
 O X U -0 0 1 Sta n dar d  V ari a nt  
 Pr oce d ure R o o m  
 O X U 0 0 1 C o njI n cisi o n  V aria nt ( wit h 
i ncisi o n of C o nj u ncti va / Te n o ns) 
 S ur gicall y e q ui p pe d Pr oce d ure R o o m  
 C o m bi nati o n Sta n dar d  Varia nt  
f oll o we d b y C o njI n cisi o n Varia nt i n 
o ne Treat me nt Sessi o n  
 O perati n g R o o m  
 I V T Oz ur de x 
 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 5 4  of  1 6 9  
1.  
A ntise ptic a p plie d f or Disi nfecti o n  
1. 1  
Please select w hi c h a ntise ptic a ge nt has b ee n use d:  
1.  
P o vi d o ne I o di ne  
2.  
C hl or he xi di ne  
3.  
Ot her  
4.  
If ot her, ple ase s pecif y: 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
2.  
T y pe of A nest hesi a gi ve n  
2. 1  
W hic h f or ms of a nest hesia were a d mi nistere d: ( m ore t ha n 1 c h oice p ossi ble)  
1.  
T o pical Tetracai ne e ye dr o ps  
2.  
Li d ocai ne Gel  
3.  
Li d ocai ne Ple d gets  
4.  
S u bte n o n Li d ocai ne  
5.  
Ot her  
If ot her, ple ase s pecif y t h e ot her a n est hetic(s) or f or ms of a nest hesia i ncl u di n g l ocati o n of 
i njecti o n (e. g., q ua dra nt f or i njecti o n a nest hesia) :  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
2. 1. 1  If ple d gets , w as t here a re peat a d mi nistrati o n of ple d gets?  
1.  
Ye s;  
If yes, pleas e s pecif y t he t otal n u m ber  of re p eat a d mi nistrati o ns of ple d gets: 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
2.  
N o  
2. 1. 2 If ple d gets , pleas e s pecif y q ua dra nt w here a p plie d ( m ore t ha n 1 selecti o n p ossi ble) 
1.  
s u peri or –  te m p oral  
2.  
s u peri or - nas al  
3.  
i nferi or –  te m p oral 
4.  
i nferi or –  nas al  
 
2. 1. 3   If s u bte n o n, pleas e s pecif y q ua dra nt w here a p plie d ( m ore t ha n 1 s electi o n p ossi ble 

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1.  
s u peri or –  te m p oral  
2.  
s u peri or - nas al  
3.  
i nferi or - te m p oral 
4.  
i nferi or - n asal  
3.  
E xec uti o n of t he O x ul u mis Pr oce d ure  
3. 1  
Was t he pr o ce d ure , d uri n g t his sessi o n,  perf or me d s uccessf ull y i n t he first atte m pt?  
1.  
Yes  
2.  
N o  
3. 1. 1   If “ N o ”, h o w ma n y atte m pts di d y o u nee d i n t otal u ntil y o u perf or me d a c o m plete 
pr oce d ure wit h a d mi nistrati o n of t he trial dr u g: _ _ _ _ _ _  
3. 1. 2  If “N o ”, select all t hat a p pl y f or t he differe nt atte m pts t hat di d n ot res ult i n 
a d mi nistrati o n of t he trial dr u g : 
1.  
C o ul d n ot or o nl y i ns ufficie ntl y e n ga ge s clera wit h t he be vel  
2.  
I c o ul d e n ga g e t he sclera, b ut t he cat heter di d n ot d e pl o y 
3.  
T he cat het er de pl o ye d s u bc o nj u ncti vall y  
4.  
T he cat het er de pl o ye d i ntra vitreall y  
5.  
Ot her  
If ot her, ple ase s pecif y  t h e “ Ot her” reas o n(s) t h e pr oce d ure was n ot p erf or me d 
s uccessf ull y o n t he first atte m pt: 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 3  H o w ma n y differe nt de vices were o pe n e d  f or t he pr oce d ure? 
1.  
1  
2.  
2  
3.  
3  
4.  
Ot her, pleas e s pecif y n u m ber: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 4  H o w ma n y differe nt de vi ces were  use d  (i.e., t he de vice t o uc he d t he s u bjects e ye 
d uri n g a pr oce d ural atte m pt)  u ntil s uccessf ul c o m pleti o n of t he pr oce d ure .  

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1.  
1  
2.  
2  
3.  
3  
4.  
Ot her, pleas e s pecif y n u m ber:  
3. 1. 4 . 1 
If 2, 3 , or ot hers is tic ke d, please briefl y s u m marize: 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 4 . 2 
Pr o vi de a reas o n f or e xc h a n gi n g De vice 1  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 4 .2. 1  Kit n u m ber  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 4. 3  
Pr o vi de a reas o n f or e xc h a n gi n g De vice 2  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 4 .3. 1  Kit n u m ber  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 4. 4   
Pr o vi de a reas o n f or e xc h a n gi n g f urt her d e vices 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
3. 1. 4. 4. 1  Please pr o vi de f urt her Kit n u m bers  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
4.  
L oc ati o n of t he I nserti o n P oi nt  
4. 1  
W hic h Q ua dra nt was c h ose n  f or t he dr u g a d mi nistrati o n 
1.  
s u peri or –  te m p oral  
2.  
s u peri or - nas al  
3.  
i nferi or - te m p oral 
4.  
i nferi or –  nas al  
 

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4. 2   
I n w hic h sect or f oll o wi n g t he 1 2 sect ors of a cl oc k or watc h dial , was t he i nserti o n 
p oi nt l ocate d  
□ 
1 2: 0 0  
□ 
1: 0 0  
□ 
2: 0 0  
□ 
3: 0 0  
□ 
4: 0 0  
□ 
5: 0 0  
□ 
6: 0 0  
□ 
7: 0 0  
□ 
8: 0 0  
□ 
9: 0 0  
□ 
1 0: 0 0  
□ 
1 1: 0 0  
4. 3  
Was a n i ncisi o n of t he c o nj u ncti va/te n o n(s) perf or me d  
1.  
Yes  
2.  
N o  
If yes, briefl y descri be d t he i ncisi o n tec h ni q ue a n d t he size of t he o p e ni n g: 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
4. 4  
At w hic h dista nce fr o m t he li m b us was t he tr ocar i nserte d:  
Please tic k t he ri g ht cate g or y  

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1.  
4 m m  
2.  
5 m m  
3.  
Ot her  
If ot her, ple ase s pecif y t h e dista nce fr o m t he li m b us was t he tr ocar i nserte d i n 
m m 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
5.  
I nserti o n (t o be c o m plet e d f or c o m plete d pr oce d ures) 
5. 1  
At w hic h a n gle relati ve t o t he base of t he e ye was t he tr ocar i nserte d i nt o t he sclera ? 
1.  
< 1 0°  
2.  
1 0 -1 5°  
3.  
1 6 -3 0°  
4.  
> 3 0°  
5. 2  
Inserti o n c o m plete d t hr o u g h t he sclera  
1.  
Yes  
2.  
N o  
5. 4  
Diffic ult y (tic k as a p pr o priate ( or dr o p d o w n)  
1.  
ver y eas y  
2.  
eas y  
3.  
s o me w hat eas y 
4.  
diffic ult  
5.  
ver y diffic ult  
5. 5  
C o m plicati o ns (tic k as a p plica ble)  

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1.  
N o c o m plicati o ns  
2.  
I ns erti o n nee dle c o ul d har dl y pass t he sclera 
3.  
Cat heter directl y de pl o ye d w he n tri g ger presse d ( n o f urt her a d v a nce me nt 
necessar y)  
4.  
Ot her  
If ot her, ple ase s pecif y 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
6.  
De pl o y m e nt  (t o be c o m plete d f or c o m plete d pr oce d ures) 
6. 1  
Was t he de pl o y me nt of t he cat het er t o t he s u prac h or oi dal s pace c o m plete d as i nte n de d ? 
1.  
Yes  
2.  
N o  
6. 2  
Fr o m de pl o ye d micr ocat heter: Was t he li g ht visi ble as e x pecte d a n d s uffici e ntl y bri g ht ? 
1.  
Yes  
2.  
N o  
6. 3  
Was t he s pee d of de pl o y me nt d uri n g t he pr oce d ure as i nitiall y set? 
1.  
Yes  
2.  
N o  
6. 4  
A n y ki n k i n t he t u bi n g?  
1.  
Yes  
2.  
N o  
 
6. 4. 1.    If 'Yes ', ple ase s pecif y d etails a n d pres u me d reas o n (s) f or t he ki n k i n t he t u bi n g? 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. I njecti o n of dr u g vi a t he dr u g li ne  (t o be c o m plete d f or c o m plete d pr o ce d ures) 

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7 .1  
Was t he i njecti o n c o m plete d as e x pecte d?  
1.  
Yes  
2.  
N o  
7. 1. 1  
If N o, i n dicate w h y t he i njecti o n was n ot c o m plet e d as e x pecte d: 
1.  
Micr ocat het er cl o g ge d b y dr u g a n d i njecti o n c o ul d n ot be c o m plete d  
2.  
Ot her ( ple ase s pecif y)  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 2  
W hat was t he ti me i nter v al f or t he dr u g i njecti o n:  
1.  Less t ha n 1 0 sec  
2.  1 0 -1 4 sec  
3.  1 5 -1 9 sec  
4.  2 0 -2 4 sec  
5.  2 5 -3 0 sec  
6.  L o n ger t ha n 3 0 sec  
7. 3  
W hat was t he resi de nce ti me of t he cat het er i n t he s u prac h or oi dal s p ace after 
c o m pleti o n of t he i njecti o n?  
1.  Less t ha n 1 0 sec  
2.  1 0 -1 4 sec  
3.  1 5 -1 9 sec  
4.  2 0 -2 4 sec  
5.  2 5 -3 0 sec  
6.  L o n ger t ha n 3 0 sec  
7 .4  
Di d t he patie nt feel p ai n d uri n g t he i njecti o n  
1. Yes  
2. N o  
7. 4. 1  
If Yes, w he n di d t he pai n start 
1.  
Wit h t he tr ocar’s ti p i nserti o n i nt o t he sclera  
2.  
Wit h tr ocar a d va nce me nt i nt o t he sclera  
3.  
Wit h cat heter de pl o y me nt  

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4.  
Wit h me dicati o n i njecti o n  
5.  
Wit h cat heter wit h dra wal  
6.  
After pr oce d ure c o m pleti o n  
7.  
Ot her, pleas e s pecif y  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 5  
H o w l o n g di d t he pai n last?  E nter d urati o n i n mi n utes  
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 6  
Was a n y me dicati o n or i nter ve nti o n perf or me d t o alle viate pai n?  
1.  
Yes  
2.  
N o  
7. 6. 1     If yes, pleas e s pecif y a n y me dicati o n or i nter ve nti o n t hat was perf or m e d t o   
alle viate pai n.  ( Ple as e re p ort o n Pri or a n d C o nc o mit a nt Me dic ati o n C R F) 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 7  
W here is t he i njecti o n l ocate d i n rel ati o n t o t he maj or reti nal la n d mar ks ( pl ease tic k all 
t hat a p pl y) 
1.  i nserti o n p oi nt 
2.  arca d es  
3.  a nteri or t o e q u at or  
4.  e q uat or  
5.  p osteri or t o e q uat or  
6.  o ptic ner ve  
7.  Ot her, pleas e s pecif y  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
7. 8  
A n y refl u x?  
1.  
Yes  
2.  
N o  

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7. 8. 1 If yes. S pecif y:  
1.  ver y mil d, < 1 0 %  
2.  mil d 1 0 t o < 2 0 %  
3.  s o me w hat 2 0-< 4 0 %  
4.  Mar ke d, 4 0 -< 6 0 %  
5.  Ver y Mar ke d 6 0 a n d m or e %  
 
7. 9  
Diffic ult y t o i nject t he st u d y dr u g  
1.  
ver y eas y,  
2.  
eas y,  
3.  
s o me w hat eas y,  
4.  
diffic ult,  
5.  
ver y diffic ult  
7. 1 0  
Were t h ere a n y c o m plicati o ns  w hile i njecti n g t he st u d y dr u g?  
6.  
Yes  
7.  
N o  
7. 1 0. 1  If ' C o m plicati o ns' is e q ual t o ' Yes' , select all co m plicati o ns, t hat a p pl y : 
1.  
I ntr a vitreal dr u g de p osit 
2.  
C o nj u ncti val dr u g de p osit  
3.  
Disc o n nect of M erit s yri n ge  
4.  
Cat heter cl o g ge d b y O X U -0 0 1  
5.  
Ot her  
  If ot her, ple ase s pecif y : 
 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 1 1  
Blee di n g  
7. 1 1. 1  A n y i ntra oc ular bl ee di n g  
1.  
Yes  
2.  
N o  
7. 1 1. 2  If ' Yes', localizati o n of t h e blee di n g : 
1.  
vitre o us  

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2.  
reti nal 
3.  
s u breti nal 
4.  
C h or oi dal/s u prac h or oi dal  
If ' A n y i ntra o c ular ble e di n g' occ urre d,  pleas e pr o vi de details : ( Ple ase re p ort as a n A dverse 
Eve nt)  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 1 1. 4  A n y scleral d a ma ge  
1.  
Yes  
2.  
N o  
If ' A n y scleral da ma g e' o cc urre d,  pleas e pr o vi de details:  ( Ple ase re p ort as a n A dverse 
Eve nt)  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 1 1. 5  A n y cli nicall y rele v a nt c o nj u ncti val he m orr ha g e  
1.  
Yes  
2.  
N o  
 
If ' A n y cli nicall y rele va nt c o nj u ncti val he m orr ha g e  occ urre d,  please pr o vi d e details:  
( Ple ase re p ort as a n A d verse Eve nt)  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
7. 1 1. 6  A n y ot her da ma g e, pleas e select t he o nes t hat a p pl y: ( Ple ase re p ort as a n A dverse 
Eve nt)  
1.  
Tra u matic cataract  
2.  
Reti nal detac h me nt  
3.  
Reti nal brea k  
4.  
Ot her  
If ot her, ple ase s pecif y: 

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
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•  Ot her oc ular s ur geries ( e. g., s q ui nt s ur ger y or 
c o nju ncti val  perit o m y) wit h p ote ntial i m pact o n scleral 
access i n t he s u perior te m p oral q ua dra nt , please s pecif y 
 L o w  
 Me di u m  
 Hi g h  
 
 
 

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C o ncl usi o n:  
O verall Assess me nt of E x pecte d Pr oce d ural C o m ple xit y ( E x pert J u d g me nt)  
T he O x ul u mis Pr oce d ure i n t he c urre nt s u bjects is e x pecte d t o h a ve  
 L o w  c o m ple xit y  
 Me di u m  c o m ple xit y  
 Hi g h  c o m ple xit y  
T he pr oce d ure is t heref ore pla n ne d t o be perf or m e d ( please tic k as a p plica ble): *  
 I n-cli nic  
 a P r oce d ure R o o m  
 a S ur gicall y E q ui p pe d Pr oce d ure R o o m  
 an  O perati n g R o o m  
T he pla n ne d i nitial pr oce d ural varia nt, if t he s u bj ect is i n a O X U-0 0 1 tr eat me nt ar m is:  
 Sta n dar d Vari a nt  
 C o njI ncisi o n Varia nt  
If a 2n d treat me nt sessi o n w o ul d be nee d e d, t he s u bject w o ul d be treate d i n 
 a S ur gicall y E q ui p pe d Pr oce d ure R o o m  
 a n O perati n g R o o m  
 

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1 3  Refere nces  
Aller ga n I nc. 2 0 1 4 ( Versi o n 2 0 2 0). ' Oz ur de x U S PI'.  
A u g usti n , A. J., M. D. Bec ker, K. Hatz, H. Ka y ma k, a n d A. S hirla w. 2 0 2 1. ' Assess me nt of 
Rei njecti o n N u m bers a n d I nter vals f or Dia betic M ac ular E d e ma Patie nts W h o 
Recei ve d De xa met has o n e I ntra vitreal I m pla nts i n Ger ma n y a n d S witzerla n d', Cli n 
O p ht h al m ol , 1 5: 3 9 5 7-6 7.  
Ba n d oli, G., K. Pal mste n, C. J. F or bess S mit h, a n d C. D. C ha m bers. 2 0 1 7. ' A Re vie w of 
S yste mic C ortic oster oi d Use i n Pre g na nc y a n d t he Ris k of Select Pre g na nc y a n d Birt h 
O utc o mes', R he u m Dis Cli n N ort h A m , 4 3: 4 8 9-5 0 2.  
Bara kat, M. R., C. C. Wy k off, V. G o nzal ez, A. H u, D. Marc us, E. Z a valeta, a n d T. A. Ci ulla. 
2 0 2 1. ' S u prac h or oi dal C L S -T A pl us I ntra vitreal Afli berce pt f or Dia betic Mac ular 
E de ma: A Ra n d o mize d, D o u ble -Mas ke d, Parallel -Desi g n, C o ntr olle d St u d y', 
O p ht h al m ol Reti n a , 5: 6 0-7 0.  
B o yer , D. S., Y. H. Yo o n, R. Belf ort, Jr., F. Ba n dell o, R. K. Mat uri, A. J. A u g usti n, X. Y. Li, H. 
C ui, Y. Has ha d, S. M. W hitc u p, a n d Mea d St u d y Gr o u p Oz ur de x. 2 0 1 4. ' T hree -y ear, 
ra n d o mize d, s ha m-c o ntr olle d trial of de xa met has o ne i ntra vitreal i m pla nt i n patie nt s 
wit h dia betic mac ular e d e ma', O p ht h al m ol o gy , 1 2 1: 1 9 0 4-1 4.  
C ha n g, T. S. 2 0 0 9. ' S u prac h or oi dal Dr u g Deli ver y via Cat heter: A Me dic o -S ur gical A p pr oac h 
t o Wet A M D', Reti n a S u m mit 2 0 0 9 A bstr act B o ok : 1-5.  
Cli nical Trials Facilitati o n a n d C o or di nati o n Gr o u p. 2 0 2 0. ' Rec o m me n dati o ns relate d t o 
c o ntrace pti o n a n d pre g n a nc y testi n g i n cli nical trials', He a ds of Me dici nes A ge ncies 
H o me p a ge : 1-1 0.  
E hlers, J. P., S. Ye h, M. G. Ma g uire, J. R. S mit h, P. Mr ut h y u nja ya, N. Jai n, L. A. Ki m, C. Y. 
We n g, C. J. Fla xel, S. D. Sc h oe n ber g er, a n d S. J. Ki m. 2 0 2 1 . 'I ntra vitreal 
P har mac ot hera pies f or Dia betic Mac ular E de ma: A Re p ort b y t he A merica n Aca d e m y 
of O p ht hal m ol o g y', O p ht h al m ol o gy , 1 2 9: 8 8-9 9.  
E ur o pea n Parlia m e nt/ C o u ncil ( E C). 2 0 1 7. ' R E G U L A TI O N ( E U) 2 0 1 7/ 7 4 5 O F T H E 
E U R O P E A N P A R LI A M E N T A N D O F T H E C O U N CI L o n me dical de vices', Offici al 
J o ur n al of t he E ur o pe a n U ni o n : 1-1 7 5.  
Fraser -Bell, S., L. L. Li m, A. Ca m pai n, H. Me hta, C. Ar o ne y, J. Br ya nt, J. Li, G. J. Q ui n, I. L. 
Mc Allister, a n d M. C. Gillies. 2 0 1 6. ' Be vaciz u ma b or De xa met h as o ne I m pla nts f or 
D M E: 2 -year R es ults ( T he B E V O R D E X St u d y)', O p ht h al m ol o gy , 1 2 3: 1 3 9 9-4 0 1.  
Me dical De vic e C o or di n ati o n Gr o u p ( M D C G). 2 0 2 0. ' Safet y re p orti n g i n cli nical 
i n vesti gati o ns of me dical de vices u n der t he Re g ul ati o n ( E U) 2 0 1 7/ 7 4 5': 1-1 6.  
Ritti p hair oj, T., T. A. Mir, T. Li, a n d G. Vir gili. 2 0 2 0. 'I ntra vitreal ster oi ds f or mac ular e de ma 
i n dia betes', C oc hr a ne D at a b ase Syst Rev , 1 1: C D 0 0 5 6 5 6. 
Rizz o, S., F. G. E bert, E. D. Bart ol o, F. Barca, F. Cresti, C. A u g usti n, a n d A. A u g usti n. 2 0 1 2. 
' S u prac h or oi dal dr u g i nf usi o n f or t he treat me nt of se vere s u bf o veal h ar d e x u dates', 
Reti n a , 3 2: 7 7 6-8 4.  

O X U C T -1 0 2 Cli nical Trial Pr ot oc ol U S v 4 . 0 2 7  Oct  2 0 2 3
 
 
O x ular Li mite d  
C O N FI D E N TI A L  
Pa ge 1 6 9  of  1 6 9  
Tetz, M., S. Rizz o, a n d A. J. A u g usti n. 2 0 1 2. ' Safet y of s u b mac ular s u prac h or oi dal dr u g 
a d mi nistrati o n via a micr ocat heter: retr os pecti ve a nal ysis of E ur o pea n tr eat me nt 
res ults', O p ht h al m ol o gic a , 2 2 7: 1 8 3-9 . 
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n U ni o n. 2 0 0 1. ' DI R E C TI V E 
2 0 0 1/ 2 0/ E C o n t he a p pr o xi mati o n of t he la ws, re g ulati o ns a n d a d mi nistrati ve 
pr o visi o ns of t he Me m ber States relati n g t o t he i m ple me ntati o n of g o o d cli nical 
practice i n t he c o n d uct of cli nical trials o n me dici nal pr o d ucts f or h u ma n us e'.  
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n U ni o n. 2 0 1 1. ' Detaile d g ui da nce 
o n t he c ollecti o n, verific ati o n a n d prese ntati o n of a d verse e v e nt/reacti o n re p orts 
arisi n g fr o m cli nical trials o n me dici nal pr o d ucts f or h u ma n use ( ‘ C T-3’ )', Offici al 
J o ur n al of t he E ur o pe a n U ni o n , C 1 7 2/ 1: 1-1 3.  
T he W H O Cataract Gra di n g Gr o u p. 2 0 0 2. ' T he W H O Si m plifie d Cataract Gra di n g S yste m', 
W H O P u blis hi n g : 1-3 2.  
T h ylef ors, B., L. T. C h ylac k, Jr., K. K o n ya m a, K. Sasa ki, R. S per d ut o, H. R. Ta yl or, S. West, 
a n d W. H. O. Cat aract Gra di n g Gr o u p. 2 0 0 2. ' A si m plifie d cataract gra di n g s yste m', 
O p ht h al mic E pi de mi ol , 9: 8 3-9 5.  
U S F D A. 2 0 1 2. ' Safet y Re p orti n g Re q uire me nts f or I N Ds a n d B A/ B E St u dies - G ui da nce f or 
I n d ustr y a n d I n vesti gat ors': 1-3 2.  
U S F D A. 2 0 1 6. ' C ollecti o n of Race a n d Et h nicit y Data i n Cli nical Trials - G ui da nce f or 
I n d ustr y': 1-2 0.  
U S F D A. 2 0 2 1a. 'I n vesti gat or Res p o nsi bilities -Safet y Re p orti n g f or I n vesti gati o nal Dr u gs 
a n d De vic es  - ( Draft) G ui da nce f or I n d ustr y': 1-1 4.  
U S F D A. 2 0 2 1 b. ' S p o ns or Res p o nsi bilities - Safet y Re p orti n g Re q uire me nts a n d Safet y 
Assess me nt f or I N D a n d Bi oa vaila bilit y/ Bi oe q ui vale nce St u dies - Draft G ui da nce f or 
I n d ustr y': 1-4 4.  
Wy k off, C. C., R. N. K h ura na, S. I. R. La m pe n, G. N or o n ha, D. M. Br o w n, W. C. O u, S. R. 
Sa d da, a n d H ul k St u d y Gr o u p. 2 0 1 8. ' S u prac h or oi dal Tria mci n ol o ne Acet o ni de f or 
Dia betic Mac ul ar E de m a: T he H U L K Trial', O p ht h al m ol Reti n a , 2: 8 7 4-7 7.  
Ye h, S., R. N. K h ura na, M. S ha h, C. R. He nr y, R. C. Wa n g, J. M. Kiss ner, T. A. Ci ulla, G. 
N or o n ha, a n d Peac htr ee St u d y I n vesti gat ors. 2 0 2 0. ' Efficac y a n d Safet y of 
S u prac h or oi dal C L S -T A f or Mac ular E de ma Sec o n dar y t o N o ni nfecti o us U veitis: 
P hase 3 Ra n d o miz e d Tri al', O p ht h al m ol o gy , 1 2 7: 9 4 8-5 5.