Clinical trial NCT04697758
Conditions: Diabetic Macular Edema (DME)
Keywords: AsclepiX macular edema DME eye diseases retinal diseases AXT107 diabetes duration of action dose escalation diabetic retinopathy retinal degeneration
Sponsor: AsclepiX Therapeutics, Inc.
Start date: 2020-12-10; Completion date: 2022-10-01
Enrollment: 6 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This study is an open-label, dose-escalating, 48-week study assessing the safety, tolerability, bioactivity and duration of action of a single intravitreal injection of 0.1 mg, 0.25 mg, or 0.5 mg AXT107 in approximately 18 subjects (up to 6 subjects per dose) with Diabetic Macular Edema (DME).

Detailed description:
Upon providing informed consent, subjects will be sequentially enrolled into the study. Decision regarding dose escalation will be based on the recommendation from the Data Monitoring Committee (DMC). The first 3 eligible subjects will receive the low dose of AXT107 injection. After the 3 low dose subjects complete a 7-day follow-up, the DMC will review their safety data. If an acceptable safety profile is determined by the DMC, 3 additional subjects will be enrolled to receive the mid dose of AXT107 injection. Upon completion of a 7-day follow-up, review of the safety data, and determination of an acceptable safety profile by the DMC for the mid dose subjects, 3 additional subjects will be enrolled to receive the high dose of AXT107 injection.

Arms: arm 1: AXT107 0.1 mg/eye arm 2: AXT107 0.25 mg/eye arm 3: AXT107 0.5 mg/eye
Interventions: intervention 1: AXT107 0.1 mg intervention 2: AXT107 0.25 mg intervention 3: AXT107 0.5 mg
Intervention descriptions: intervention 1: Single intravitreal injection of AXT107 0.1 mg/eye intervention 2: Single intravitreal injection of AXT107 0.25 mg/eye intervention 3: Single intravitreal injection of AXT107 0.5 mg/eye

Protocol documents:
Prot_SAP_001.pdf: 
As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
A S C L E PI X  T H E R A P E U TI C S,  I N C. 
 
P h ase 1/ 2 a St u d y of t he S afet y a n d Bi o acti vit y of A X T 1 0 7 i n S u bjects wit h Di a betic  
M ac ul ar  E de m a ( D M E)  
 
St u d y A b bre viate d  
Titl e  
C O N G O  st u d y 
 
Pr ot oc ol  N u m ber:  
A X T 1 0 7 -C S 1 0 1  
St u d y  P hase:  
1/ 2a  
U S  I N D #:  
 
I n vesti gati o nal Pr o d uct:  A X T 1 0 7  
 
S p o ns or N a me a n d  
A d dress:  
 
 
Seri o us  A d verse  E ve nt  
Re p orti n g:  
Me dical Saf et y  
P h ysicia n C o nta ct  
I nf or mati o n: 
 
I n vesti gat or 
A gree me nt:  
 
 
 
 
 
 
 
P RI N CI P A L  
I N V E S TI G A T O R: 
Ascle pi X T hera p e utics, I nc.  
3 0 1  W  2 9 t h Str eet,  S uite  2 0 0 4  
Balti m ore, M D  2 1 2 1 1  
safet y gr o u p @cli ni pace.c o m 
Q ua n D o n g N g u ye n, M D  
E mail: safet y @ascl e pi x.c o m 
P h o ne:  1 -4 1 0 -8 0 2 -8 3 2 1  
I ha ve rea d t he c o nt e nt of t his cli nical pr ot oc ol a n d a gree t o m ai nt ai n 
c o nfi de ntialit y of all i nf or mati o n r ecei ve d or de v el o p e d i n c o n ne cti o n  
wit h t his pr ot oc ol. I a gre e t o c o n d uct t he st u d y i n c o m plia n ce wit h t he  
cli ni cal pr ot oc ol, G C P, t he et hi cal pri n ci pl es c o ntai n e d wit hi n t h e  
Declarati o n of Helsi n ki, a n d all a p plica ble re g ulat or y re q uire m e nts. I  
a gree t o i nitiat e t his st u d y o nl y u p o n o btai ni n g writt e n a p pr o val b y t h e  
a p pr o priat e I R B or E C, a n d o n ce I ha ve c o m plie d wit h all fi na ncial a n d  
a d mi nistr ati v e  re q uir e me nts of t h e g o ver ni n g b o d y of t he cli nic al 
i nstit uti o n a n d t he S p o ns or.  
 
 
Si g nat ure/ Date:  
/ 
 
Na me:  
A d dress:  
P h o ne:  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
A B B R E VI A TI O N S  
A D A  
A nti -Dr u g  A nti b o d y  
A E  
A d verse  E ve nt  
A M D  
A ge -relat e d Mac ular  De ge ner ati o n  
B C V A  
Best  C orrect  Vis ual  Ac uit y  
C R F  
Case  Re p ort  F or m  
C R O  
Cli nic al  R esearc h  Or ga niz ati o n  
C S T  
Ce ntral  S u bfiel d  T hic k ness  
D F E  
Dilate d  F u n d us  E xa mi nati o n  
D M C  
Data  M o nit ori n g  C o m mittee  
D M E  
Dia beti c  Mac ular  E d e ma  
D R S S  
Dia beti c  Reti n o pat h y  Se verit y  Scale  
E T D R S  
Earl y Tr eat me nt Dia b eti c Reti n o pat h y St u d y  
F A  
Fl u oresc ei n  A n gi o gr a p h y  
F D A  
F o o d  a n d Dr u g  A d mi nistrati o n  
F P  
F u n d us  P h ot o gra p h y  
G C P  
G o o d  Cli ni cal  Practice  
H b A 1c  
He m o gl o bi n  A 1c  
H G F  
He pat oc yt e  Gr o wt h  Fact or  
I C F 
I nf or me d C o nse nt  
I C H 
I nter nati o nal C o nfere n ce  o n  Har m o ni zati o n  
I E C 
I n de pe n de nt Et hics  C o m mitte e  
I G F-1  
I ns uli n Gr o wt h  Fact or -1  
I N D 
I n vesti gati o nal Ne w  Dr u g  
I O P 
I ntra oc ul ar Press ure  
I R B 
I nstit uti o n al R e vie w  B oar d  
m g  
Milli gra m  
m m H g  
Milli m eters  Mer c ur y  
M O P  
Ma n ual  of  Pr oce d ures  
M T D  
Ma xi m u m  T oler ate d  D ose  
N/ A  
N ot  A p plica ble  
n A M D  
Ne o vasc ular  ( wet) A ge -Relat e d  Mac ular  De ge nerati o n  
N F -k B  
N uclear Fact or ka p pa -li g ht-c h ai n-e n h a ncer of acti vat e d B cells  
O C T -A  
O ptical  C o her e nce T o m o gra p h y A n gi o gr a p h y  
O U  
B ot h  E yes  
P D G F  
Platel et  Deri ve d  Gr o wt h  Fact or  
P T  
Preferre d  Ter m  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  3  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
S A E  
Seri o us  A d verse  E ve nt  
S D -O C T  
S pectral D o m ai n O pti cal C o h ere nce T o m o gra p h y  
S E  
St u d y  E ye  
S O C  
S yste m  Or ga n  Class  
Tie 2  
T yr osi ne ki nase wit h i m m u n o gl o b uli n -li k e a n d e pi der mal gr o wt h fa ct or-li ke 
V E G F R 2  
Vasc ular  E n d ot helial Gr o wt h Fa ct or  Rec e pt or 2  
V E G F  
Vasc ular  E n d ot helial  Gr o wt h  Fact or  
V E -P T P  
Vasc ular  E n d ot helial  Pr otei n  T yr osi n e  P h os p hatase  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  4  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
1.  S Y N O P SI S  
 
S p o ns or:  
As cle pi X  T hera pe utics,  I nc. 
Na me  of  I n vesti gati o nal Pr o d uct:  
A X T 1 0 7  
St u d y  P has e:  
1/ 2a  
Na me  of  Acti ve  I n gre die nts: 
A X T 1 0 7 is a 2 0 -mer s y nt hetic pe pti de deri ve d fr o m t he n o n -c olla ge n o us d o mai n of c olla ge n I V t hat i n hi bits  
V E G F -A,  V E G F -C  a n d acti vates Tie 2. 
St u d y  Title:  
P has e  1/ 2a  St u d y  of  t he Safet y  a n d Bi oacti vit y  of  A X T 1 0 7  i n S u bjects  wit h  Dia betic  M ac ular  E de ma  ( D M E) 
–  C O N G O  st u d y 
O bjecti ves:  
Pri mar y  O bjecti ve:  
T o  e val uate  t he s afet y a n d t olera bilit y of  a  si n gle i njecti o n of  t hree d os e  le vels ( 0. 1 m g/e ye,  0. 2 5  m g/e ye,  or  
0. 5 m g/e ye) of A X T 1 0 7 i n s u bjects wit h D M E  
Sec o n dar y  O bjecti ve:  
T o  e val uate  t he bi oacti vit y  a n d d urati o n  of  acti o n  of  A X T 1 0 7  f or t he treat me nt of  D M E  
M et h o d ol o g y:  
T his is a n o pe n -la bel, d os e-es calati n g, 4 8 -wee k st u d y ass essi n g t he s afet y, t olera bilit y, bi oacti vit y a n d 
d urati o n of acti o n of a si n gle i ntra vitreal i njecti o n of 0. 1 m g (l o w d os e), 0. 2 5 m g ( mi d d os e), or 0. 5 m g ( hi g h  
d os e)  A X T 1 0 7  i n a p pr o xi matel y  1 8  s u bjects ( u p t o 6  s u bjects per  d os e)  wit h D M E.  
U p o n pr o vi di n g i nf or me d c o ns e nt, s u bjects will be se q ue ntiall y e nr olle d i nt o t he st u d y. De cisi o n re gar di n g  
d os e escalati o n will be base d o n t he rec o m me n dati o n fr o m t he Data M o nit ori n g C o m mittee ( D M C). T he first  
3  eli gi ble  s u bjects will  recei ve t he l o w d os e  of  A X T 1 0 7  i njecti o n. After  t he 3 l o w  d os e  s u bjects c o m plete  a 
7 - da y f oll o w -u p, t he D M C will re vie w t heir s afet y data. If a n acce pta ble s afet y pr ofile is deter mi ne d b y t he  
D M C, 3 a d diti o nal s u bjects will be e nr olle d t o recei ve t he mi d d os e of A X T 1 0 7 i njecti o n. U p o n c o m pleti o n  
of a 7 -da y f oll o w-u p, re vie w of t he s afet y data, a n d deter mi nati o n of a n acce pta ble s afet y pr ofile b y t he  
D M C f or t he mi d d os e s u bjects, 3 a d diti o nal s u bjects will be e nr olle d t o recei ve t he hi g h d os e of A X T 1 0 7  
i njecti o n. F or t he first 9 s u bjects, treat me nt naï ve patie nts C A N N O T be e nr olle d. After t he 9 i nitial s u bjects 
ha ve c o m plete d t he 7 -da y f oll o w -u p, 9 a d diti o nal s u bjects ( 3 eac h t o recei ve t he l o w d os e, mi d d os e, a n d  
hi g h d os e of t he st u d y dr u g) w h o ca n be pre vi o usl y treate d or treat me nt naï ve ma y be e nr olle d. I n t otal,  
a p pr o xi matel y 1 8 s u bjects wit h D M E will be e nr olle d a n d will be f oll o we d f or 4 8 we e ks. If t he ma xi m u m  
t olerate d d os e  ( M T D) is n ot  reac he d after t he 0. 5  m g  gr o u p,  a  hi g her  d os e  u p  t o 1. 0  m g  ma y  be  teste d. 
All s u bjects will atte n d a t otal of 1 6 visits: Scree ni n g ( Da y -1 4 t o -1), B as eli ne ( Da y 0), Da y 1 ( P h o ne call),  
Wee k  1,  Wee k  4,  Wee k  8,  Wee k  1 2,  Wee k  1 6,  Wee k  2 0,  Wee k  2 4,  Wee k  2 8,  Wee k  3 2,  Wee k  3 6,  Wee k  4 0,  
Wee k  4 4 a n d  Wee k  4 8.  
St o p pi n g  r ules will  be  c o nsi dere d  u p o n  D M C  decisi o n  if a n y of  t he f oll o wi n g e ve nts  are  i de ntifie d: 
•  
Decreas e i n Earl y Treat me nt Dia betic R eti n o pat h y St u d y ( E T D R S) best c orrecte d vis ual ac uit y  
( B C V A) of ≥ 1 5 letters ( 3-li ne decreas e) u nrelate d t o t he nat ural pr o gressi o n of t he dis eas e a n d 
deter mi ne d  b y  t he I n vesti gat or t o be  relate d t o t he st u d y dr u g  i n ≥ 2  s u bject 
•  
I ntra oc ular i nfla m mati o n (a nteri or or  p osteri or)  gra de  + 2  or  m or e  i n ≥ 2  s u bjects ( usi n g S U N  
Gra di n g  W or ki n g  Gr o u p  a n d N uss e n blatt  et al gra di n g)  
•  
I ncreas e i n i ntra oc ular press ure  (I O P) t o ≥ 3 0 m m H g  f or m ore  t h a n 2 4  h o urs  p ost -i njecti o n i n ≥ 2  
s u bjects des pite  I O P l o weri n g me dicati o n  treat me nt 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  5  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
•  
A n y  ot her  s eri o us oc ular  or  s yste mic a d verse  e ve nt ( A E) t hat, i n t he o pi ni o n  of  t he I n vesti gat or, is 
relate d t o t he st u d y dr u g i n  ≥ 1 s u bject  
R es c ue t hera p y wit h t he I n vesti gat or’s preferre d treat me nt will be all o we d starti n g at Wee k 1 2 f or a n y  
s u bject w h o has recei ve d i njecti o n of A X T 1 0 7 a n d f or w h o m t here is ≥ 7 letter E T D R S B C V A decreas e  
fr o m B as eli ne ( Da y 0) or ≥ 7 5 µ m i ncreas e i n C e ntral S u bfiel d t hic k ness ( C S T) c o m pare d t o t he l o west 
pre vi o us  visit.  
N u m ber  of  S u bjects:  
A p pr o xi matel y 1 8 s u bjects wit h dia betic mac ular e de ma sec o n dar y t o t y pe 1 or t y pe 2 dia betes mellit us will  
be e nr olle d. T he fi nal n u m ber of s u bjects e nr olle d ma y be a dj uste d bas e d o n t he pres e nce of d ose li miti n g  
t o xicities. 
D urati o n  of  t he St u d y:  
T he  e x pecte d d urati o n  of  t his cli nical st u d y is u p  t o 5 0  wee ks,  i ncl u di n g a  1 4 -da y  s cree ni n g p has e  a n d 4 8  
wee ks  of  o n  treat me nt/ f oll o w u p  p has e.  
I ncl usi o n a n d E xcl usi o n  Criteria:  
I ncl usi o n Criteria:  
1.  1 8  years  of  a ge  or  ol der  
2.  T y pe 1 or 2 dia betes mellit us wit h ce nter -i n v ol ve d D M E a n d wit h ce ntral s u bfiel d t hic k ness ≥ 3 0 5 
µ m (fe males) or 3 2 0 µ m ( males) o n S pectralis ® S pectral D o mai n O ptical C o here nce T o m o gra p h y  
( S D-O C T)  de vice or 2 9 0 µ m (fe males) or 3 0 5 µ m ( males) o n Cirr us ®  S D -O C T de vice a n d wit h  
i ntrareti nal or s u breti nal fl ui d as e vi de nce d b y S pectral D o mai n O ptical C o here nce T o m o gra p h y 
( S D-O C T)  i n t he st u d y e ye  at Scree ni n g,  as  c o nfir me d  b y  t he I n vesti gat or 
3.  B C V A i n t he st u d y e ye at B as eli ne ( Da y 0) bet wee n 6 5 a n d 2 3 E T D R S letters ( 2 0/ 4 0 a n d 2 0/ 3 2 0  
S nelle n e q ui vale nt) wit h B C V A decre me nt deter mi ne d b y t he I n vesti gat or pri maril y attri b uta ble t o  
D M E  
4.  B C V A of 3 4 E T D R S letters or better ( 2 0/ 2 0 0 or better S nelle n e q ui vale nt) i n t he n o n -st u d y e ye at 
B as eli ne  ( Da y 0)  
5.  A ble a n d willi n g t o gi ve si g ne d i nf or me d c o ns e nt a n d f oll o w st u d y i nstr ucti o ns  
E xcl usi o n  Criteria:  
1.  A n y si g ns of hi g h ris k pr oliferati ve dia betic reti n o pat h y i n t he st u d y e ye a n d relate d c o m plicati o ns,  
as  deter mi ne d  b y  t he I n vesti gat or 
2.  Pre vi o usl y  treate d patie nts  w h o  are  n o n -res p o n ders t o a nti-V E G F  deter mi ne d  b y  t he I n vesti gat or 
3.  Pa nreti nal p h ot oc oa g ulati o n wit hi n 6 m o nt hs or mac ular las er p h ot oc oa g ulati o n wit hi n 3 m o nt hs  
fr o m Scree ni n g i n  t he st u d y e ye 
4.  Us e of i ntra oc ular or peri oc ular c ortic oster oi ds wit hi n 4 m o nt hs ( wit h t he e xce pti o n of fl u oci n ol o ne  
acet o ni de i ntra vitreal i m pla nt w hic h is e xcl u de d), Afli berce pt wit hi n 8 we e ks, R a ni biz u ma b a n d  
B e vaciz u ma b  wit hi n  6  wee ks  fr o m B as eli ne  ( Da y 0)  i n t he st u d y e ye  
5.  A n y c o nc urre nt dis ease t hat w o ul d re q uire me dical or s ur gical i nter ve nti o n d uri n g t he st u d y i n t he  
st u d y e ye (e. g. reti nal detac h me nt,  si g nifica nt cataract,  u nc o ntr olle d  gla uc o ma)  
6.  A n y c o n diti o n t hat t hat ma y precl u de i m pr o ve me nt i n vis ual ac uit y or affect t he e val uati o n of t he  
st u d y e ye after res ol uti o n of D M E (e. g. vitre o us he m orr ha ge, mac ular is c he mia, pre -reti nal fi br osis 
i n v ol vi n g t he mac ula, pre-reti nal mac ular he m orr ha ge, vis uall y si g nifica nt vitre o mac ular tracti o n, 
or  me dia clarit y i ns ufficie nt  t o o btai n  q ualit y i ma ges)  
7.  C hr o nic  u veitis  or  o n g oi n g  cli nicall y  si g nifica nt i nfecti o n or  i nfl a m mati o n (e. g. keratitis,  s cleritis) 
i n eit her e ye 
8.  Pre vi o us vitre oreti nal s ur ger y, pre vi o us filtrati o n s ur ger y, catar act s ur ger y wit hi n 3 m o nt hs or Y A G  
las er ca ps ul ot o m y  wit hi n  1  m o nt h  of  Scree ni n g  i n t he st u d y e ye 
9.  Hist or y  of  cataract  s ur ger y c o m plicati o ns  ( vitre o us l oss) or  a p ha kia  i n t he st u d y e ye 


As cle pi X T hera pe utics, I nc.  
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1 0.  Hist or y  of  pe netrati n g  oc ular  tra u ma i n t he st u d y e ye  
1 1.  Hist or y  of  aller g y  t o fl u ores cei n or  p o vi d o ne  i o di ne 
1 2.  Hist or y  or  c urre nt s yste mic c o n diti o n  t hat precl u de  t he s afe a d mi nistrati o n  of  t he st u d y treat me nt or  
c o nf o u n d res ults (e. g. H b A 1c > 1 2 % at Scree ni n g, u nc o ntr olle d h y perte nsi o n [ ≥ 1 8 0/ 1 0 0] o n  
o pti mal me dical re gi me n at Scree ni n g, s yste mic a nti -V E G F tre at me nt, re nal fail ure re q uiri n g  
dial ysis,  or re nal  tra ns pla nt) 
1 3.  W o me n of c hil d beari n g p ote ntial w h o are pre g na nt, n ursi n g, pla n ni n g a pre g na nc y, or n ot usi n g a  
me dicall y acce pta ble  f or m of  birt h  c o ntr ol  
1 4.  Partici pati o n  i n a n i nter ve nti o nal cli nical  st u d y at Scree ni n g  
I n vesti gati o nal Pr o d uct,  D os e,  a n d R o ute  of  A d mi nistrati o n:  
S u bjects  will  recei ve o ne  of  t he f oll o wi n g d os es  of  A X T 1 0 7  si n gle i ntra vitreal i njecti o n i n t he st u d y e ye. 
•  
A X T 1 0 7  0. 1 m g  (l o w d os e)  
•  
A X T 1 0 7  0. 2 5  m g  ( mi d d ose)  
•  
A X T 1 0 7  0. 5 m g  ( hi g h d os e)  
C o ntr ol Pr o d uct, D os e, a n d R o ute of A d mi nistrati o n:  
N/ A  
Safet y  Ass ess me nts:  
•  
A d vers e  e ve nts  ( A Es) 
•  
E T D R S  B C V A  
•  
I O P 
•  
Slit  la m p bi o micr os c o p y  
•  
Dilate d  f u n d us e xa m ( D F E) 
•  
O pt os  (at s electe d sites o nl y)  
•  
S D -O C T  
•  
O C T -A  (at s electe d sites o nl y)  
•  
F u n d us  p h ot o gra p h y  ( F P) 
•  
Fl u ores cei n  a n gi o gra p h y  ( F A) 
•  
Dia betic  R eti n o pat h y  Se verit y  Scale  ( D R S S) 
•  
La b orat or y  e val uati o n  (i ncl u di n g A D A  ass a y) 
•  
Vital  si g ns 
•  
P h ysical  e xa mi nati o ns 
•  
Pre g na nc y  test 
Efficac y  Ass ess me nts:  
•  
C S T  ( M ea n c ha n ge  i n C S T  fr o m B as eli ne)  ass esse d  b y  S D -O C T  a n d  meas ure d  b y  R ea di n g  C e nter  
•  
B C V A  ( M ea n c ha n ge  i n E T D R S  letters) 
•  
B C V A  ( Pr o p orti o n i m pr o vi n g ≥5,  ≥1 0,  a n d ≥1 5  letters fr o m B as eli ne  ( Da y 0)  
Statistical  M et h o ds:  
Sa m ple  Size  Deter mi nati o n:  
A p pr o xi matel y 1 8 s u bjects will be e nr olle d, wit h 6 s u bjects i n eac h d os e. T he fi nal n u m ber of s u bjects  
e nr olle d ma y be a dj uste d bas e d o n t he prese nce of d ose li miti n g t o xicities. T his s a m ple size is n ot pla n ne d  
bas e d  o n  statistical c o nsi derati o ns. 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  7  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
A nal ys es:  
A ge, s e x, race, et h nicit y, a n d baseli ne ass ess me nts will be s u m marize d a n d liste d b y d os e le vel. M e dical  
hist or y,  hist or y  of  oc ular  s ur ger y a n d pr oce d ures,  a n d c o nc o mita nt  me dicati o n  will  als o be  s u m marize d a n d 
liste d. 
C ha n ges fr o m bas eli ne i n B C V A ( E T D R S letter sc ore) a n d reti nal t hic k ness ( C S T) will be s u m marize d b y  
d os e le vel usi n g c o nti n u o us s u m mar y statistics. B C V A c ha n ge will be s u m marize d usi n g cate g orical  
s u m maries as  well,  i ncl u di n g fre q ue nc y c o u nts a n d  perce nta ges  i m pr o vi n g at least 5,  1 0,  a n d 1 5  letters. 
Ver bati m des cri pti o ns of A Es will be ma p pe d t o M e d D R A t hesa ur us ter ms a n d be prese nte d i n a data listi n g.  
Treat me nt e mer ge nt A Es t hat occ ur after t he first d os e of st u d y me dicati o n will be s u m marize d b y d os e le vel 
usi n g fre q ue nc y a n d perce nt f or eac h s yste m or ga n class ( S O C) a n d preferre d ter m ( P T) wit hi n eac h S O C.  
S u m maries will be pres e nte d s e paratel y f or oc ular a n d n o n -oc ular A Es. All T E A Es will be s u m marize d b y  
s e verit y a n d st u d y dr u g relate d ness. 
B C V A will be s u m marize d at eac h ti me p oi nt usi n g b ot h c o nti n u o us s u m maries ( E T D R S letter sc ore),  
i ncl u di n g c ha n ge  fr o m B as eli ne  ( Da y 0),  a n d cate g orical  s u m maries, i ncl u di n g c ha n ge  fr o m B as eli ne  ( Da y 0)  
o n  a n E T D R S  c hart i n t he n u m ber  of li nes.  
I O P will be s u m marize d at eac h ti me p oi nt usi n g b ot h c o nti n u o us s u m maries, i ncl u di n g c ha n ge fr o m 
B as eli ne  ( Da y 0),  a n d cate g orical s u m maries f or pre -state d cate g ories  of  c ha n ge  i n I O P. 
Slit la m p bi o micr os c o p y a n d o p ht hal m os c o p y meas ures will be s u m marize d at eac h meas ure d ti me p oi nt 
usi n g cate g orical  s u m mar y statistics. 
F A  will  be  s u m marize d b y  visit.  
D R S S  will  be  s u m marize d at eac h meas ure d  visit  a n d c ha n ge  fr o m B aseli ne  ( Da y 0)  t o eac h meas ure d  visit.  
Vital si g ns will be s u m marize d at eac h visit a n d f or c ha n ge fr o m B as eli ne ( Da y 0) t o eac h visit usi n g  
c o nti n u o us  s u m mar y statistics b y treat me nt gr o u p  a n d visit.  
Cli nical la b orat or y res ults will be s u m marize d usi n g b ot h c o nti n u o us s u m maries, i ncl u di n g c ha n ge fr o m  
B as eli ne ( Da y 0), a n d dis crete s u m maries, i ncl u di n g fre q ue nc y a n d perce nt of s u bjects wit h a n a b n or mal  
val ue  a n d s hift ta bles fr o m B as eli ne  ( Da y 0).  A d diti o nall y,  la b orat or y data  will  be  pres e nte d  i n data  listi n gs. 
E x pl orat or y a nal ys es will be perf or me d t o s u m marize t he res ults o btai ne d fr o m t he N otal Visi o n H o me O C T  
de vice  a n d h o me  M & S
®  T ec h n ol o g y  vis ual  ac uit y meas ure me nt.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  8  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
2.  T A B L E  O F  C O N T E N T S  
A B B R E VI A TI O N S  ....................................................................................................................................... 2  
1.  
S Y N O P SI S  ............................................................................................................................................ 4  
2.  
Ta ble  of C o nte nts  .................................................................................................................................. 8  
2. 1  
Ta ble  of Ta bles  ............................................................................................................................ 1 0  
2. 2  
Ta ble  of Fi g ures  ........................................................................................................................... 1 0  
3.  
B A C K G R O U N D  ................................................................................................................................ 1 1  
3. 1  
I ntr o d ucti o n.................................................................................................................................. 1 1  
3. 2  
I n vesti gati o nal Pr o d uct  ................................................................................................................ 1 2  
3. 3  
S u m mar y  of Rele va nt Data  .......................................................................................................... 1 2  
3. 4  
K n o w n  Ris ks  a n d Be nefits  t o H u ma n S u bjects  ........................................................................... 1 3  
3. 5  
Tar get  P o p ulati o n  ......................................................................................................................... 1 3  
4.  
S T U D Y  O BJ E C TI V E S  ....................................................................................................................... 1 4  
5.  
I N V E S TI G A TI O N A L P L A N  ............................................................................................................. 1 4  
5. 1  
O verall  St u d y  Desi g n  ................................................................................................................... 1 4  
5. 1. 1  
St u d y  Meas ures  .................................................................................................................... 1 5  
5. 1. 2  
Meas ures  t o Mi ni mize Bias  ................................................................................................. 1 5  
5. 1. 3  
Tr e at me nt  Assi g n me nt a n d  D ose  Escalati o n Criteria  .......................................................... 1 5  
5. 1. 4  
Criteria  f or Ter mi nati o n of t he St u d y  ( St o p pi n g R ules)  ...................................................... 1 6  
5. 2  
S electi o n  a n d Wit h dra wal of St u d y  S u bje cts  ............................................................................... 1 6  
5. 2. 1  
S u bje ct  I ncl usi o n Criteria .................................................................................................... 1 6  
5. 2. 2  
S u bje ct  E xcl usi o n Criteria  ................................................................................................... 1 6  
5. 2. 3  
S u bje ct  Wit h dra wal Criteria  ................................................................................................ 1 7  
5. 3  
Tr e at me nt  of S u bje cts  .................................................................................................................. 1 8  
5. 3. 1  
St u d y  Dr u g  A d mi nistrati o n  .................................................................................................. 1 8  
5. 3. 2  
Deter mi nati o n  of t he  St u d y E ye ........................................................................................... 1 8  
5. 3. 3  
Resc ue  T hera p y .................................................................................................................... 1 8  
5. 3. 4  
C o nc o mita nt  Me dic ati o n ...................................................................................................... 1 8  
5. 3. 5  
Tr e at me nt  C o m plia nce  ......................................................................................................... 1 8  
5. 3. 6  
Restricti o ns  .......................................................................................................................... 1 8  
5. 4  
St u d y  Dr u g  Ma na ge me nt  a n d Ha n dli n g  ...................................................................................... 1 8  
5. 4. 1  
I n vesti gati o nal Dr u g  ............................................................................................................ 1 8  
5. 4. 2  
St u d y  Dr u g Pac ka gi n g a n d  La beli n g  ................................................................................... 1 9  
5. 4. 3  
St u d y  Dr u g St ora ge  .............................................................................................................. 1 9  
5. 4. 4  
A d diti o nal  Cli nic al S u p plies  ................................................................................................ 1 9  
5. 4. 5  
St u d y  Dr u g  Ac c o u nta bilit y  .................................................................................................. 1 9  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  9  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
5. 4. 6  
Ret ur n  of U n use d S u p plies  .................................................................................................. 1 9  
5. 5  
Assess me nt  of Safet y  ................................................................................................................... 1 9  
5. 5. 1  
Defi niti o ns  a n d classific ati o n of  A d verse  E ve nts  ................................................................ 1 9  
5. 5. 2  
C olle cti o n  a n d Assess me nt of  A d verse  E ve nts .................................................................... 2 0  
5. 5. 3  
Re p orti n g  of  A d verse  E ve nts  ............................................................................................... 2 2  
5. 5. 4  
A d diti o nal  S afet y Assess me nts  ............................................................................................ 2 2  
5. 6  
Assess me nt  of Effic ac y  ................................................................................................................ 2 5  
5. 6. 1  
Ce ntral  S u bfiel d T hic k ness  .................................................................................................. 2 5  
5. 6. 2  
Best  C orre cte d Vis ual Ac uit y  .............................................................................................. 2 5  
5. 7  
C o nti n ge nc y  Meas ures  i n Case of a  Gl o bal  E mer ge nc y  .............................................................. 2 5  
6.  
S T A TI S TI C A L  A N A L Y SI S P L A N  ................................................................................................... 2 6  
6. 1  
A nal ysis  P o p ulati o ns .................................................................................................................... 2 6  
6. 2  
Statistic al  H y p ot heses  .................................................................................................................. 2 6  
6. 3  
Statistic al  Met h o ds  ....................................................................................................................... 2 6  
6. 4  
S a m ple  Size  Deter mi nati o n  ......................................................................................................... 2 7  
6. 5  
Ha n dli n g  of  Missi n g Data  ............................................................................................................ 2 7  
6. 6  
I nteri m A nal yses  .......................................................................................................................... 2 7  
7.  
D A T A  M A N A G E M E N T  A N D  A D MI NI S T R A TI V E R E Q UI R E M E N T S  ....................................... 2 7  
7. 1  
C o m pleti o n  of S o urce  D oc u me nt a n d Case  Re p ort F or ms  .......................................................... 2 7  
7. 2  
Q ualit y  C o ntr ol a n d Q ualit y Ass ura nc e  ....................................................................................... 2 8  
7. 3  
Data  Ha n dli n g a n d Rec or d  Ke e pi n g  ............................................................................................ 2 8  
8.  
E T HI C S  ............................................................................................................................................... 2 8  
8. 1  
Et hics  Re vie w  .............................................................................................................................. 2 8  
8. 2  
Et hic al  C o n d uct of St u d y  ............................................................................................................. 2 9  
8. 3  
I nf or me d C o nse nt a n d S u bje ct C o nfi de ntialit y  ........................................................................... 2 9  
9.  
I N V E S TI G A T O R O B LI G A TI O N S  ................................................................................................... 2 9  
9. 1  
Dir e ct  Ac cess  t o S o urc e Data/ D oc u me nts  ................................................................................... 2 9  
9. 2  
Fi na nci n g  a n d I ns ura nce .............................................................................................................. 2 9  
9. 3  
Re c or d  Rete nti o n  ......................................................................................................................... 3 0  
9. 4  
C o nfi de ntialit y  Discl os ure  a n d P u blic ati o n  P olic y  ...................................................................... 3 0  
1 0.  BI B LI O G R A P H Y  A N D  S E L E C T E D  R E F E R E N C E S  ...................................................................... 3 1  
A p pe n dic es  .................................................................................................................................................. 3 3  
A p pe n di x  I. 
S c he d ule  of  Visits  a n d Pr oc e d ures................................................................................... 3 3  
A p pe n di x  II. 
A p pr o val Si g nat ures  ........................................................................................................ 3 4  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 0  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
2. 1  T a ble  of  T a bles  
Ta ble  I-1  Sc he d ule  of  Visits  a n d Pr oc e d ures  ............................................................................................... 3 3  
2. 2  T a ble  of  Fi g ures  
Fi g ure  1  
St u d y  Sc he mati c  ......................................................................................................... 1 4  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 1  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
3.  
B A C K G R O U N D  
3. 1  I ntr o d ucti o n 
T he w orl d wi de pre v ale nc e of dia b etes was esti mat e d t o be m ore t ha n 8. 5 % i n 2 0 1 7, f or a t otal of  
4 5 1 milli o n pe o pl e affe cte d ( G uari g u ata 2 0 1 4). Wit h a n a gi n g p o p ul ati o n a n d i ncre asi n g  
pre vale n ce  of  o besit y, it  is esti m ate d t hat 5 9 2  milli o n pe o ple  will  h a ve dia b etes  i n 2 0 3 5.  A  
meta -a nal ysis  of  3 5  p o p ulati o n -base d  st u di es w orl d wi de  s u g gests t hat al m ost 7 %  of  t he dia betic  
p o p ulati o n h as dia betic mac ular e de ma ( D M E) ( Ya u 2 0 1 2). D M E occ urs d ue t o reti nal  
micr o vasc ulat ur e da ma g e, i ncr ease i n v asc ular p er m ea bilit y, a n d l oss of bl o o d -reti n al barri er 
lea di n g t o i nt erstitial fl ui d a cc u m ul ati o n i n t he r eti n a, partic ularl y i n t he re gi o n of t he mac ula 
( C u n ha-Vaz  1 9 7 5, Patelli 2 0 1 4, B ha gat 2 0 0 9).  
 
I n D M E, vasc ular per me a bilit y, a n gi o ge nesis, a n d i nfla m m ati o n pla y a n i m p ort a nt r ole ( C a m pa 
2 0 1 0, B ha gat 2 0 0 9). Reti nal h y p o xia a n d t he h y p o xi a -re g ulate d pr otei n vasc ul ar e n d ot h eli al 
gr o wt h fact or ( V E G F) pla y ke y r ol es i n t he p at h o ge n esis of D M E ( N g u ye n 2 0 0 4, N g u ye n 2 0 0 9).  
I ntra vitr eal i njecti o n (I V T) of a V E G F ne utr ali zi n g pr otei n, eit her i n t he f or m of a n a nti b o d y or a 
c hi meric re ce pt or, is first -li ne treat me nt f or D M E a n d pr o vi des be nefit i n m a n y patie nts ( N g u ye n 
2 0 0 6, N g u ye n 2 0 1 2,), b ut t here is a s u bst a nti al perc e nta ge of patie nts ( 4 0 t o 6 0 %) i n w h o m a nti - 
V E G F i nje cti o ns ar e n ot s ufficie nt t o eli mi nate e d e m a or pr o vi de a cli nicall y si g nifi ca nt  
i m pr o ve m e nt i n vis ual a c uit y ( H eier 2 0 1 4, K or o bel ni k 2 0 1 4). T hese patie nts m a y e x peri e nce 
per ma ne nt re d ucti o ns i n vis ual ac uit y o ver ti me fr o m t he da m a gi n g eff ects of c hr o ni c, rec urr e nt  
e de ma ( D o 2 0 1 3, C ha n n a 2 0 1 4). T here is t h us still a n u n met m e dic al ne e d f or a ge nts t o treat  
D M E  usi n g n o vel mec ha nis ms.  
 
I n a d diti o n t o V E G F i n hi biti o n, Ti e 2 ( T yr osi ne ki nas e wit h i m m u n o gl o b uli n-li k e a n d e pi der mal 
gr o wt h fact or -li ke d o m ai ns 2) is als o bei n g i ncre asi n gl y rec o g ni ze d f or its r ole i n re g ulati n g 
vasc ular per mea bilit y. Tie 2 is a t yr osi ne ki nase re ce pt or t hat, li ke V E G F rec e pt or -2, is l oc ate d o n  
vasc ular e n d ot helial c ells a n d h as bee n i m pli cat e d i n t he m o d ul ati o n of v asc ular per mea bilit y  
( W o n g 1 9 9 7, T h urst o n 1 9 9 9, T h urst o n 2 0 0 0). H o we ver, alt h o u g h p h os p h or yl ati o n of V E G F 
rece pt or-2 sti m ul ates vasc ul ar le a ka ge, p h os p h or yl ati o n of Tie 2 a cti v ates d o w nstre a m p at h wa ys  
t hat s u p press vasc ular lea ka g e a n d pr o m ote vasc ular sta bili zati o n. A n gi o p oieti n 1 is a n 
e n d o ge n o us f ull a g o nist t hat sti m ulat es p h os p h or ylati o n of Tie 2 ( Da vis 1 9 9 6). A n gi o p oieti n 2 is  
a n e n d o ge n o us wea k, partial a g o nist t h at c o m pet es wit h a n gi o p oieti n 1, t her e b y s u p pressi n g Tie 2  
p h os p h or ylati o n ( Mais o n pi erre 1 9 9 7, Y ua n 2 0 0 9). Ti e 2 is als o re g ul ate d b y v asc ular e n d ot helial  
pr otei n t yr osi n e p h os p hatase ( V E -P T P), als o k n o w n as h u ma n pr otei n t yr osi ne p h os p hatase bet a,  
w hic h is p h ysicall y ass ociate d wit h Tie 2. It d e p h os p h or ylates Tie 2, t h ere b y re d uci n g Ti e 2  
acti v ati o n a n d si g nali n g t hr o u g h t h e Tie 2 p at h wa y ( Yac ys h y n 2 0 0 9). Le vels of b ot h a n gi o p oieti n  
2 a n d V E -P T P are i ncr ease d b y h y p o xia, lea di n g t o a cce nt u ate d V E G F -me diate d o c ular  
ne o vasc ularizati o n a n d vasc ular l ea ka g e ( Hac kett 2 0 0 0, Hac kett 2 0 0 2, Os hi m a 2 0 0 4, Os hi ma  
2 0 0 5, S he n 2 0 1 4). Precli ni cal m o dels ha ve s h o w n t h at V E -P T P i n hi biti o n, e v e n i n t h e prese nce  
of  hi g h a n gi o p oieti n 2, rest or es Tie 2  a cti vati o n  ( S he n 2 0 1 4). 
 
T he dr u gs c urre ntl y use d t o tre at D M E are a d mi nistere d I V T a n d t he y h a ve a s h ort d urati o n of  
acti o n; L uc e ntis ®  is a d mi nistere d e v er y m o nt h a n d E ylea®  is a d mi nistere d m o nt hl y i nitiall y, a n d 
if t here is a n a de q uate res p o nse it ma y b e d ose d e ver y 2 m o nt hs or a d mi nistere d e ver y 3 m o nt hs.  
Fre q ue nt d osi n g is a b ur de n f or p ati e nts a n d ca n als o i ncrease t he c ha n ce of a d v erse effe cts  
relat e d t o t h e i nj ecti o n. T h us, t h ere  is a c o nsi der a ble u n met  me dical n ee d  f or alter nati ve 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 2  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
treat me nt o pti o ns wit h pr ol o n g e d treat me nt d urati o n t o re d uce treat me nt b ur d e n a n d ne w 
mec ha nis m of acti o n f or patie nts w h o c o ul d n ot ac hi e ve o pti mal treat me nt effect fr o m a nti- 
V E G F  a g e nts.  
 
Ascle pi X T hera p e utics, I nc. is de vel o pi n g A X T 1 0 7 I ntra vitr eal I njecti o n f or t he treat me nt of  
reti nal diseases, i n cl u di n g dia betic m ac ul ar e de ma ( D M E), ne o vasc ular a ge-r elate d m ac ul ar 
de ge nerati o n  ( n A M D), a n d reti nal vei n  occl usi o n  ( R V O). A X T 1 0 7  is a s y nt hetic 2 0 -mer  
c olla g e n I V – deri ve d pe pti de w hi c h i n hi bits Vasc ular E n d ot helial Gr o wt h Fact or Rece pt or 2  
( V E G F R 2) a n d acti vates t he vessel sta bilizi n g t yr osi ne ki nase re ce pt or Tie 2. A X T 1 0 7 disr u pts 
i nte gri n α v β 3 t o i n hi bit si g nali n g fr o m V E G F R 2 a n d ot her gr o wt h fact ors, i ncl u di n g P D G F, 
H G F, a n d I G F; c o nse q u e ntl y, c h or oi dal ne o vasc ul ari zati o n a n d vasc ul ar lea k a ge ar e i n hi bite d.  
A X T 1 0 7 disr u pts α 5 β 1 a n d sti m ulat es t he rel o cati o n of Tie 2 a n d t he i nte gri n s u b u nit α 5 t o c ell  
j u ncti o ns. A X T 1 0 7 t he n acti vat es j u ncti o nal Tie 2 b y c o n verti n g t he A n g 2 t hat is a b u n da nt i n 
t hese diseases i nt o a str o n g a g o nist, t here b y u pr e g ulati n g d o w nstrea m s ur vi v al si g nals, 
rearra n gi n g F a cti n t o stre n gt he n j u ncti o ns, a n d, as a res ult, re d uci n g e n d ot h elial j u ncti o nal 
per mea bilit y. I n a d diti o n, A X T 1 0 7 res ol ves T N F α -i n d uce d vasc ul ar i nfla m mati o n i n e n d ot helial 
cells b y c o n v erti n g t he pr o -i nfl a m m at or y A n g 2 i nt o a str o n g a g o nist of Tie 2 si g nali n g, disr u pti n g 
t he s y ner gis m bet wee n T N F α a n d A n g 2 w hile als o pre ve nti n g I κ B α de gra d ati o n directl y t hr o u g h  
Tie 2  si g nali n g. T his  rec o v er y of  I κ B α pre ve nts  N F -κ B  n uclear  l oc ali zati o n, t here b y bl oc ki n g  
N F -κ B i n d uce d i nfla m mat or y res p o nses. A d mi nister e d i ntra vitre all y, A X T 1 0 7 has a nti - 
a n gi o ge ni c, a nti -per me a bilit y, a n d a nti -i nfla m mati o n effect a n d i n d uces re gr essi o n of disease i n 
a ni mal m o dels  of  reti n al ne o vasc ulari zati o n  ( Mira n d o 2 0 2 0, Sil va  2 0 1 7,  F or mic a  2 0 1 9).  
 
T his P hase 1/ 2a, o pe n -la bel, d ose-escal ati n g, 4 8 -we e k st u d y is pla n ne d t o assess t he safet y,  
t olera bilit y, bi oa cti vit y,  a n d d urati o n  of  acti o n  of  a si n gle i ntra vitre al i nj ecti o n of  A X T 1 0 7  i n t he 
st u d y e ye of s u bjects wit h D M E. 
 
3. 2  I n vesti g ati o n al Pr o d uct  
A X T 1 0 7  is a 2 0 -mer  s y nt hetic pe pti d e  ma de  u p  of  nat urall y -o cc urri n g  a mi n o aci ds  de vel o pe d  as  
a first-i n-class s y nt heti c pe pti de t hat i n hi bits V E G F R 2 a n d acti vat es Tie 2 as a m o n ot her a p y  
a ge nt.  
 
A X T 1 0 7 will be a d mi nister e d via a n i ntra vitre al i nje cti o n (I V T) t o p atie nts wit h D M E. B ase d o n  
a vail a ble p h ar ma c o d y na mic a n d p h ar ma c o ki netics d ata, t hr ee d oses, 0. 1 m g/ e ye, 0. 2 5 m g/e ye, 0. 5  
m g/e ye  will  be teste d i n  t his cli ni cal st u d y. 
 
3. 3  S u m m ar y  of  Rel e v a nt  D at a  
A brief s u m mar y of t h e fi n di n gs fr o m n o n cli nical st u dies is prese nte d b el o w. Please r efer t o t he  
I n vesti gat or’s Br oc h ure f or d etaile d  st u d y i nf or m ati o n. 
 
A X T 1 0 7 was teste d i n t he g e netic tet/ o psi n/ V E G F m o use m o del i n w hi c h hi g h l e vels of h u m a n  
V E G F ca use m assi ve vasc ul ar lea k a ge l ea di n g t o e x u dati ve r eti n al detac h m e nt. I n t his m o use  
m o del, A X T 1 0 7 pre ve nts reti n al det ac h m e nt m or e p ote ntl y t ha n afli ber ce pt. A X T 1 0 7 als o  
str o n gl y i n hi bits isc he mia-i n d u ce d reti nal n e o vasc ul arizati o n i n a n o x y ge n-i n d uc e d reti n o pat h y 
( OI R) m o del i n t h e m o use. I n t h e ra b bit e ye n o ncli ni cal st u di es, A X T 1 0 7 str o n gl y i n hi bite d 
V E G F  i n d u ce d vasc ul ar  lea k a ge. Re m ar ka bl y,  i n hea d -t o-hea d  st u dies i n w hi c h  A X T 1 0 7  was  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 3  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
teste d at a h u m a n d ose e q ui vale nt of afli b erce pt i n t h e ra b bit e ye, A X T 1 0 7 i n hi bite d vasc ular 
lea ka g e m or e  p ote ntl y  t ha n afli berc e pt a n d its acti vit y  laste d at least t wi ce as  l o n g as  afli ber ce pt.  
 
I n a d diti o n, A X T 1 0 7 was test e d i n a reti n o pat h y of pre mat urit y m o d el of a n gi o ge nesis i n t he 
m o use e yes. T he r es ults s h o we d t hat A X T 1 0 7 i n hi bit e d a n gi o ge n esis i n d uce d b y h y p o xia i n a  
d ose -de pe n de nt ma n ner. T his s u g geste d t hat A X T 1 0 7 ca n be use d t o i n hi bit ne o vasc ulariz ati o n  
ca use d  b y h y p o xia.  
 
Re gar di n g t h e acti vati o n of Ti e 2, A X T 1 0 7 was teste d i n a reti n o pat h y of pr e mat urit y m o use  
m o del f or p h os p h or ylati o n of Tie 2. T he st u d y s h o we d t hat A X T 1 0 7 i n d uc e d t he p h os p h or yl ati o n  
of Tie 2 w he n it is prese nt i n c o n diti o ns of h y p o xia i n w hic h HI F, V E G F a n d A n g 2 ar e all  
i ncrease d. T his res ult s u g gest e d t hat A X T 1 0 7 c a uses a n i ncre ase i n Tie 2 p h os p h or ylati o n i n t h e 
prese nce  of i ncr ease d  A n g 2 w hic h  n or mall y ca uses  a decrease  i n Tie 2 p h os p h or ylati o n.  
 
A X T 1 0 7 was f urt her teste d i n a m o del i n w hic h Li p o p ol ysacc hari de ( L P S) was use d t o ca use  
vasc ular l ea ka ge i n t he m o use e ye.  T his m o d el ser ves as a s urr o gate f or i nfla m mat or y diseases  
of t he e ye i ncl u di n g D M E a n d u veitis. T he res ults de m o nstrate d t hat A X T 1 0 7 i n hi bit e d L P S  
i n d uce d vasc ul ar  lea k a ge a n d h as a nti-i nfla m mati o n effect. 
 
Oc ular tiss ue distri b uti o n st u dies ha ve s h o we d t h e s ustai ne d oc ular e x p os ure of A X T 1 0 7 i n t h e  
reti na, c h or oi d, a n d vitre o us of ra b bit  e yes  f or u p t o 1 2 m o nt hs.  
 
I n t he t o xi c ol o g y st u di es i n ra b bits a n d mi ni pi gs, A X T 1 0 7 was well t ol erat e d, n o si g nific a nt 
oc ular t o xicit y was o bser ve d f or u p t o 1 5 m o nt hs i n r a b bits a n d f or u p t o 9 m o nt hs i n mi ni pi gs.  
N o s yste mic e x p os ure was det ecte d at d oses u p t o 1. 0 m g/e ye a n d n o s yste mi c t o xi cit y was  
o bser ve d.  
 
I n s u m mar y, n o ncli nic al st u di es ha ve de m o nstr ate d t hat A X T 1 0 7 is m ore p ot e nt t h a n afli berce pt, 
has  a l o n ger  effic ac y  d urati o n wit h n o detecta bl e  s yste mic e x p os ure. 
 
3. 4  K n o w n  Ris ks  a n d  Be nefits  t o H u m a n  S u bjects  
T his is t he first -i n-h u ma n cli nical trial of A X T 1 0 7. T he ris ks ass ociate d wit h A X T 1 0 7 are n ot  
well u n derst o o d at t his ti me. T he p ot e ntial ris ks relat e d t o i ntr a vitr eal i njecti o n i n cl u de  
c o nj u ncti val h y p ere mia or he m orr h a ge. E n d o p ht hal mitis, vitre o us he m orr h a ge, a n d reti nal  
detac h me nt  are u n c o m m o n  ris ks ass ociate d wit h i ntr a vitre al i nj ecti o n. 
 
T he a ntici p ate d be n efit of A X T 1 0 7 as a n e w treat me nt o pti o n wit h a differ e nt m ec ha nis m of  
acti o n is t he p ote ntial  f or a ne w  t hera p e uti c effect wit h  a pr ol o n ge d  d urati o n  of  acti o n t hat will  
ease t he b ur de n of fre q u e nt  tre at m e nts f or patie nts wit h reti n al  diseases.  
 
3. 5  T ar get  P o p ul ati o n  
T he tar g et p o p ul ati o n f or A X T 1 0 7 is dia b eti c patie nts wit h ce nter -i n v ol ve d dia betic m ac ul ar 
e de ma. I n t his st u d y, a p pr o xi mat el y 1 8 s u bjects wit h a n e xisti n g dia g n osis of ce nter -i n v ol ve d 
D M E  will be recr uit e d t o partici pat e.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 4  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
4.  S T U D Y  O B J E C TI V E S  
T he pri m ar y o bje cti ve of t his st u d y is t o e val uate t h e safet y a n d t olera bilit y of a si n gle i nje cti o n  
of  t hree d ose  le vels ( 0. 1 m g/e y e,  0. 2 5  m g/e y e,  or  0. 5  m g/e ye)  of A X T 1 0 7 i n  s u bjects wit h  D M E.  
 
T he  sec o n dar y o bje cti v e  of  t he st u d y is t o e val u ate t h e bi oacti vit y  a n d d urati o n  of  acti o n of  
A X T 1 0 7  f or t he treat me nt of D M E. 
 
5.  I N V E S TI G A TI O N A L P L A N  
5. 1  O ver all  St u d y  Desi g n  
T his is a n o pe n -l a bel, d ose-escalati n g, 4 8 -wee k st u d y assessi n g t he safet y, t olera bilit y,  
bi oacti vit y  a n d d urati o n  of  acti o n  of  a si n gle i ntr a vitr eal i nj ecti o n of  0. 1  m g  (l o w d ose),  0. 2 5  m g  
( mi d d ose), or 0. 5 m g ( hi g h d ose) A X T 1 0 7 i n a p pr o xi mat el y 1 8 s u bje cts ( 6 s u bjects per d ose) 
wit h  D M E.  
 
U p o n pr o vi di n g writte n i nf or me d c o nse nt, s u bjects will be e nr olle d i nt o t h e st u d y wit h t h e  
d ose -escalati o n strate g y as de pi cte d i n Fi g ure 1 . A t otal of 1 6 visits are pl a n ne d i n t he st u d y, 
i ncl u di n g Scr ee ni n g ( D a y -1 4 t o -1), Baseli n e ( Da y 0), a n d f oll o w -u p visits o n Da y 1 ( P h o ne  
call), Wee k 1, W ee k 4, W ee k 8, W ee k 1 2, W ee k 1 6, Wee k 2 0, W ee k 2 4, We e k 2 8, We e k 3 2,  
Wee k  3 6,  Wee k  4 0, Wee k  4 4  a n d W ee k  4 8.  Ta ble  I-1  i n A p pe n di x  I pr o vi des  a s u m mar y of t he  
st u d y visit a n d t he pr o ce d ures t o b e  perf or me d  at ea c h visit.  
 
T he st u d y dr u g will b e a d mi nister e d b y t he st u d y I n v esti gat or at Baseli ne ( Da y 0), after  
c o m pleti o n of t h e Baseli ne assess me nts, i ncl u di n g B C V A, I O P meas ure me nt, slit la m p  
bi o micr osc o p y, a n d S D -O C T. I O P will be re peat e d a n d D F E will b e c o m plet e d aft er  
a d mi nistr ati o n of t he st u d y dr u g at t he B aseli ne visit. P ost -baseli ne assess me nts will be  
c o m plete d  as  s pecifi e d i n Se cti o n  7  a n d as  descri be d  i n t he Ma n ual  of  Pr oce d ures  ( M O P). 
 
Fi g ure  1  
St u d y  Sc he m atic  
 
Scr e e ni n g  
D a y  -1 4 t o -1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 D M C re vie w of safet y data at Wee k 1. T hree s u bse q ue nt s u bjects are t o be e nr olle d t o recei ve t he ne xt hi g her treat me nt d ose  
o nl y  u p o n  c o nfir mati o n  fr o m t he D M C of acce pta ble  safet y pr ofile of t he  pre vi o us  gr o u p.  
D M C 1 
Gr o u p  1  
B as eli n e  
D 0  
D 1  
( P h o n e 
C all)  
W 4  - W 4 0  
W 1  
W 4 8  
Acc e pt a bl e  
s af et y 
D M C 1 
Gr o u p  2  
B as eli n e  
D 0  
D 1  
( P h o n e 
C all)  
W 4  - W 4 0  
 
W 4 8  
Acc e pt a bl e  
s af et y 
 
Gr o u p  3  
B as eli n e  
D 0  
D 1  
( P h o n e 
C all)  
W 4  - W 4 0  
W 1  
W 4 8  
E nr oll  A d diti o n al  S u bjs: 
Gr o u p  1:  n  = 3 
Gr o u p  2:  n  = 3 
Gr o u p  3:  n  = 3 
D 1  
( P h o n e 
C all)  
W 1  - W 4 0  
W 4 8  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 5  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
5. 1. 1  St u d y  Meas ures  
T he  Safet y  meas ures  are as  f oll o ws: 
 
•  A d verse  E ve nts  
•  E T D R S  B C V A  
•  I O P 
•  Slit  l a m p Bi o micr osc o p y  
•  D F E  
•  O pt os  (at selecte d sit es o nl y)  
•  S D -O C T  
•  O C T -A  (at selecte d sit es o nl y)  
•  F u n d us  P h ot o gra p h y  
•  Fl u oresc ei n  A n gi o gra p h y  
•  Dia beti c  Reti n o pat h y  Se verit y  Scal e  ( D R S S) 
•  Cli nic al  La bs  
•  Vital  si g ns 
•  P h ysical  e x a mi n ati o n  
•  Pre g na nc y  testi n g 
 
T he  effica c y  m eas ures  are as  f oll o ws: 
 
•  C ha n ge  i n C S T  fr o m Baseli ne  ( Da y 0)  
•  B C V A  ( Mea n c ha n ge i n E T D R S  lett ers) 
•  B C V A  ( Pr o p orti o n i m pr o vi n g ≥5,  ≥1 0,  a n d ≥1 5  letters fr o m Baseli ne  ( Da y 0)  
Refer  t o Ta bl e  I-1  i n A p pe n di x  I f or a sc he d ul e of  st u d y visits  a n d Pr oce d ures.  
 
5. 1. 2  Meas ures  t o Mi ni mize  Bi as  
T his is a n o pe n l a bel first -i n-h u m a n a n d d ose -fi n di n g st u d y. Ra n d o miz ati o n or mas ki n g is n ot 
e m pl o ye d  i n t his st u d y. 
 
5. 1. 3  Treat m e nt  Assi g n m e nt  a n d D ose  Escal ati o n  Crit eri a  
S u bjects will b e se q ue ntiall y assi g ne d t o r ecei v e eit h er t he l o w, mi d, or hi g h d ose of st u d y  
me dic ati o n, i n m ulti pl es of 3. D ecisi o n re gar di n g d ose escal ati o n will be base d u p o n t he  
rec o m m e n dati o n fr o m t h e Data M o nit ori n g C o m mitt ee ( D M C).  
 
T he first 3 eli gi ble s u bje cts will r ecei v e t he l o w d ose of A X T 1 0 7 i njecti o n ( Gr o u p 1). After  
Gr o u p 1 has c o m plet e d a 7 -da y f oll o w -u p, t he D M C will re vi e w t heir saf et y dat a. If a n 
acce pta bl e safet y pr ofile is deter mi ne d b y t h e D M C, 3 a d diti o n al s u bje cts will b e e nr olle d t o  
recei v e t he mi d d ose of A X T 1 0 7 i nje cti o n ( Gr o u p 2). U p o n c o m pleti o n of a 7-da y f oll o w -u p,  
re vie w of t he safet y dat a, a n d deter mi nati o n of a n a c ce pta ble safet y pr ofile b y t he D M C f or 
Gr o u p 2, 3 a d diti o nal s u bjects will be e nr olle d t o rec ei ve t h e hi g h d ose of A X T 1 0 7 i nj ecti o n  
( Gr o u p 3). After t h e 9 i nitial s u bjects ha v e c o m plet e d t he 7-da y f oll o w -u p, 9 a d diti o nal s u bj ects  
( 3 eac h i n eac h tr eat me nt gr o u p) ma y be e nr oll e d. If t he ma xi m u m t oler ate d d ose ( M T D) is n ot  
reac he d aft er t he 0. 5  m g  gr o u p, a hi g h er d ose  u p  t o 1. 0 m g ma y be teste d. 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 6  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
5. 1. 4  Criteri a  f or Ter mi nati o n  of  t he St u d y  ( St o p pi n g R ul es)  
T he D M C will c o n d uct o n g oi n g re vie ws of c olle cte d safet y dat a t o deter mi n e t he n ee d f or e arl y  
ter mi n ati o n of t he st u d y. St o p pi n g r ules will b e i nc or p orate d if a n y of t he f oll o wi n g e ve nts are 
i de ntifie d: 
 
•  Decrease i n Earl y Tr eat me nt Di a betic Reti n o pat h y St u d y ( E T D R S) best c orre cte d vis ual  
ac uit y ( B C V A) of ≥ 1 5 l ett ers ( 3-li ne de crease) u nr el ate d t o t he nat ural pr o gressi o n of t h e 
disease  a n d  det er mi n e d  b y  t he I n vesti g at or t o be relat e d t o t h e st u d y dr u g  i n ≥ 2 s u bjects  
•  I ntra oc ul ar i nfla m mati o n (a nteri or or  p osteri or)  gra d e  + 2  or  m ore  i n ≥ 2  s u bjects ( usi n g S U N  
Gra di n g  W or ki n g  Gr o u p  a n d N usse n blatt  et al gra di n g)  
•  I ncrease i n i ntra oc ular press ure  (I O P) t o ≥ 3 0 m m H g  f or m ore  t ha n 2 4  h o urs  p ost -i njecti o n i n 
≥ 2  s u bjects des pite  I O P l o weri n g me di cati o n  tre at m e nt 
•  A n y ot her seri o us oc ular or s yste mic a d v erse e ve nt ( A E) t hat, i n t he o pi ni o n of t he  
I n vesti gat or, is rel ate d t o t he st u d y dr u g i n ≥ 1 s u bj ect  
 
U p o n D M C’s rec o m me n dati o n f or st u d y ter mi nati o n, f urt her e nr oll me nt of st u d y s u bjects i n t he  
st u d y will be disc o nti n ue d. S u bj ect wit h dra wal pr oc e d ures m ust be f oll o we d f or all acti v e  
s u bjects t o e ns ure t h e safet y of  t he s u bj ects at t he c o ncl usi o n of t he st u d y.  
 
5. 2  Selecti o n  a n d  Wit h dr a w al  of  St u d y  S u bjects  
A p pr o xi matel y 1 8 s u bjects ma y be e nr olle d i nt o t h e st u d y, wit h 6 s u bjects i n eac h of t he l o w 
( Gr o u p 1), mi d ( Gr o u p 2), a n d hi g h ( Gr o u p 3) treat m e nt d ose ar ms. T h e first 9 se q ue ntial 
s u bjects M U S T N O T be treat me nt n aï ve. T h e a d diti o nal 9 s u bjects ca n be pre vi o usl y tre ate d or  
treat me nt naï ve.  
 
5. 2. 1  S u bject  I ncl usi o n Criteria  
1.  1 8  years of  a ge or ol der  
2.  T y pe 1 or 2 dia b etes m ellit us wit h st u d y e y e ce nt er -i n v ol ve d D M E a n d wit h c e ntral s u bfiel d 
t hic k ness ≥ 3 0 5 µ m (fe mal es) or 3 2 0 µ m ( males) o n S pectralis®  S pectr al D o mai n O ptical  
C o here nce T o m o gra p h y ( S D -O C T)  de vi ce or 2 9 0 µ m (fe males) or 3 0 5 µ m ( mal es) o n  
Cirr us ®  S D -O C T de vice a n d i ntrareti nal or s u breti n al fl ui d as e vi de nc e d b y S pectral D o mai n  
O ptical  C o here n ce  T o m o gra p h y  ( S D-O C T)  at Scree ni n g,  as  c o nfir m e d  b y  t he I n v esti gat or 
3.  B C V A i n t he st u d y e ye at Baseli ne ( Da y 0) bet we e n 6 5 a n d 2 3 E T D R S letters ( 2 0/ 4 0 a n d  
2 0/ 3 2 0 S nelle n e q ui vale nt) wit h B C V A decre me nt d eter mi ne d b y t h e I n vesti gat or pri m aril y  
attri b uta bl e t o D M E 
4.  B C V A of 3 4 E T D R S letters or better ( 2 0/ 2 0 0 or b ett er S nelle n e q ui vale nt) i n t he n o n -st u d y 
e ye at Baseli ne ( Da y 0)  
5.  A ble  a n d willi n g  t o gi ve  si g ne d i nf or me d c o nse nt a n d f oll o w st u d y i nstr ucti o ns 
 
5. 2. 2  S u bject  E xcl usi o n  Crit eri a  
1.  A n y si g ns of hi g h ris k pr oliferati ve di a betic reti n o pat h y i n t he st u d y e y e a n d relate d  
c o m pli cati o ns,  as deter mi ne d b y  t he I n vesti gat or 
2.  Pre vi o usl y treate d patie nts w h o are n o n -res p o n ders t o a nti-V E G F d eter mi ne d b y t he  
I n vesti gat or 
3.  Pa nreti nal p h ot oc o a g ulati o n wit hi n 6 m o nt hs or m ac ular laser p h ot oc oa g ulati o n wit hi n 3  
m o nt hs  fr o m Scree ni n g i n t he st u d y e ye  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 7  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
4.  Use of i ntra oc ul ar or peri oc ular c ortic ost er oi ds wit hi n 4 m o nt hs ( wit h t he e xce pti o n of  
fl u oci n ol o n e ac et o ni de i ntra vitre al i m pla nt w hic h is e xcl u de d), Afli berce pt wit hi n 8 we e ks, 
Ra ni biz u ma b  a n d Be va ciz u ma b  wit hi n  6  wee ks  fr o m Baseli ne  ( Da y 0) i n  t he st u d y e ye  
5.  A n y c o nc urre nt dise ase t hat w o ul d r e q uire me di cal or s ur gical i nter ve nti o n d uri n g t he st u d y  
i n t he st u d y e ye (e. g. r eti n al detac h m e nt, si g nifica nt catar act,  u nc o ntr olle d  gla u c o ma)  
6.  A n y c o n diti o n t h at m a y precl u de i m pr o ve me nt i n vis ual ac uit y or affe ct t h e e val uati o n of t he  
st u d y e ye aft er res ol uti o n of D M E (e. g. vitre o us he m orr ha ge, ma c ular isc h e mi a, pre -reti nal 
fi br osis i n v ol vi n g t h e ma c ula, pr e-reti n al m ac ul ar he m orr ha ge, vis uall y si g nifica nt 
vitre o m ac ul ar  tracti o n, or me dia  cl arit y i ns uffici e nt  t o o btai n  q ualit y  i ma g es) 
7.  C hr o nic u veitis or o n g oi n g cli ni call y si g nifi ca nt i nfe cti o n or i nfla m mati o n (e. g. keratitis,  
scleritis) i n eit her e y e  
8.  Pre vi o us vitre oreti nal s ur ger y, pre vi o us filtrati o n s ur ger y, cat aract s ur ger y wit hi n 3 m o nt hs  
or  Y A G  laser ca ps ul ot o m y wit hi n 1  m o nt h of  Scre e ni n g  i n t he st u d y e ye  
9.  Hist or y  of  cataract s ur ger y c o m plic ati o ns  ( vitr e o us l oss) or  a p ha kia i n t he st u d y e ye  
1 0.  Hist or y  of  pe netrati n g  o c ular  tra u ma i n t he st u d y e ye  
1 1.  Hist or y  of  aller g y  t o fl u or escei n or  p o vi d o ne  i o di ne 
1 2.  Hist or y or c urre nt s yste mic c o n diti o n t hat pre cl u de t he safe a d mi nistrati o n of t he st u d y  
treat me nt or c o nf o u n d res ults (e. g. H b A 1c > 1 2 % at Scree ni n g, u nc o ntr oll e d h y perte nsi o n [ ≥ 
1 8 0/ 1 0 0] o n o pti m al m e dic al re gi me n at Scree ni n g, s yste mic a nti -V E G F tre at m e nt, re nal  
fail ure re q uiri n g dial ysis, or re nal tra ns pla nt) 
1 3.  W o me n  of  c hil d b eari n g  p ote ntial  w h o  are pre g na nt,  n ursi n g,  pla n ni n g  a pr e g na nc y,  or  n ot  
usi n g  a me dic all y  a cce pta ble f or m of  birt h  c o ntr ol  
1 4.  Partici p ati o n  i n a n i nter v e nti o n al cli nical st u d y at Scr ee ni n g  
 
5. 2. 3  S u bject  Wit h dra wal  Crit eria  
S u bjects ma y wit h dra w fr o m partici p ati o n ( wit h dra w c o nse nt) at a n y ti me d uri n g t he st u d y,  
wit h o ut ca use, a n d re gar dl ess of circ u mst a nces. I n a d diti o n, t h e Pri nci p al I n vesti gat or or t he  
Me dical M o nit or ma y ter mi nate a s u bject’s parti ci pati o n i n t h e st u d y f or reas o ns rel ate d t o saf et y  
a n d/ or t o pr ot ect t he ri g hts a n d i nter est of t he s u bj ect. S u bjects ma y b e disc o nti n ue d fr o m t he  
st u d y d ue t o  a n y of t he f oll o wi n g r eas o ns: 
 
•  N o n -c o m plia n ce  
•  L ost  t o f oll o w-u p  
•  Pr ot oc ol  vi olati o n  
•  Wit h dra wal  b y  s u bject 
•  A Es  
•  Deat h  
•  Cli nic al  j u d g m e nt of  t he I n v esti gat or or  t he Me di cal  M o nit or  
•  Ot her  
If a s u bject is disc o nti n u e d fr o m t he st u d y bef ore c o m pleti n g t he Wee k 4 8 visit, all safet y a n d 
perf or ma nc e assess me nts sc he d ule d at t h e fi nal visit s h o ul d be perf or me d o n t he da y of 
disc o nti n uati o n, t o t he e xte nt p ossi bl e. T he fi nal assess me nts a n d t he re as o n f or disc o nti n u ati o n  
s h o ul d be d oc u me nte d i n t he s u bje ct’s rec or ds a n d t h e a p pr o priate earl y ter mi nati o n Case R e p ort  
F or ms  ( C R F). 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 8  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
S u bjects  w h o  pre mat urel y  disc o nti n u e  fr o m t he st u d y ma y  be  re place d o nl y  wit h  a p pr o val 
o btai ne d  fr o m t h e S p o ns or. 
 
5. 3  Tre at me nt  of  S u bjects  
5. 3. 1  St u d y  Dr u g  A d mi nistrati o n  
St u d y me dic ati o n will be a d mi nistere d via I V T i nj ecti o n b y a q ualifie d p h ysi cia n. S u bj ects will  
recei v e a si n gl e d ose of A X T 1 0 7 ( base d o n assi g ne d d osa ge) i n t he st u d y e ye o n Da y 0 
( Baseli ne). R efer  t o t he P har ma c y  Ma n ual  f or i nstr ucti o ns o n  t he pre parati o n  of  t he st u d y dr u g.  
 
5. 3. 2  Det er mi nati o n  of  t he St u d y  E ye  
St u d y e ye will b e defi n e d as t he e y e t hat me ets all of t he i ncl usi o n a n d n o ne of t he e xcl usi o n  
criteria. If b ot h e yes meet criteri a, st u d y e ye will be defi ne d as t h e e ye wit h t he w orse visi o n o n  
Da y 0 ( Baseli ne). If b ot h e yes ha ve t he sa m e visi o n, t he ri g ht e ye ( O D) will be deter mi ne d as t h e  
st u d y e ye. Refer  t o t he M O P  f or st u d y e ye pre parati o n  pri or  t o a d mi nistrati o n of  st u d y dr u g.  
 
5. 3. 3  Resc ue  T her a p y  
Resc ue t her a p y wit h t h e I n vesti gat or’s preferre d treat me nt will be all o we d st arti n g at We e k 1 2,  
f or a n y s u bject w h o has rec ei ve d i nje cti o n of A X T 1 0 7 a n d f or w h o m t here is ≥ 7 letter E T D R S 
B C V A decrease fr o m Baseli ne ( Da y 0) or ≥ 7 5 µ m i ncrease i n C S T c o m pare d t o t he l o west  
meas ure m e nt at a n y pre vi o us visit. It is re c o m m e n de d t hat resc u e d s u bjects c o m plete all st u d y  
f oll o w u p visits  t hr o u g h Wee k 4 8/ E xit.  
 
5. 3. 4  C o nc o mit a nt  Me di cati o n  
T here ar e n o pr o hi bite d c o nc o mit a nt m e dic ati o ns i n t he st u d y. W he n p ossi ble, c o nc o mita nt  
me dic ati o ns s h o ul d be use d wit h a c o nsist e nt d ose t hr o u g h o ut t he st u d y. T h e use of c o nc o mita nt  
me dic ati o ns ( prescri pti o n or o ver-t he-c o u nter) will b e rec or de d i n t he s o urce d o c u me nts d uri n g  
t he st u d y, usi n g t he g e neri c na me, i n dic ati o n, r o ute of a d mi nistr ati o n, fr e q ue nc y, d ose, start dat e 
a n d st o p date (if a p plic a ble).  
 
5. 3. 5  Treat m e nt  C o m pli a nce  
T he  treat me nt i n t his st u d y i ncl u des a si n gle d ose  i nj ecti o n a d mi nister e d  b y  t he st u d y 
I n vesti gat or. Me as ure me nt  of  treat me nt c o m pli a nce is n ot  a p plica bl e t o t his st u d y. 
 
5. 3. 6  Restri cti o ns  
S u bjects will b e i nstr ucte d t o r e mai n seate d f or a p pr o xi mat el y 3 0 mi n utes f oll o wi n g t he A X T 1 0 7  
I V T. S u bjects s h o ul d be a d vise d t hat t he y s h o ul d a v oi d vi g or o us e xercise s uc h as j u m pi n g ja c ks,  
aer o bics,  y o ga, lifti n g wei g hts,  etc. wit hi n a  m o nt h after  t he A X T 1 0 7  I V T. 
 
5. 4  St u d y  Dr u g  M a n a ge m e nt  a n d  H a n dli n g  
5. 4. 1  I n vesti gati o nal Dr u g  
St u d y me dic ati o n will be teste d i n 3 c o nce ntrati o ns i n t his st u d y; t he 0. 1 m g s ol uti o n is  
c o nsi dere d  t he “l o w  d ose”, t he  0. 2 5  m g  s ol uti o n is c o nsi dere d  t he “ mi d d ose”,  a n d t h e 0. 5 m g  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  1 9  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
s ol uti o n is c o nsi der e d t he “ hi g h d ose”. S yri n g es a n d nee dles will be utili ze d t o a d mi nister t he  
st u d y me dicati o n  ( Se e t he M O P  a n d P har mac y  Ma n u al  f or a d mi nistr ati o n  i nstr u cti o ns). 
 
5. 4. 2  St u d y  Dr u g  Pac ka gi n g  a n d La beli n g  
A X T 1 0 7 will be pr o vi de d as a l y o p hilize d p o w der i n a vial. T he st u d y dr u g will be rec o nstit ute d,  
as descri be d  i n t he P har m ac y  Ma n ual,  f or i njecti o n t o pr o vi de  t h e a p pr o pri ate  d ose.  T he  la bel 
will  i ncl u d e t he na m e  of  t he st u d y dr u g,  t he pr ot oc ol  n u m ber,  kit  n u m ber,  a n d st ora ge c o n diti o ns.  
T he  Cart o n  will  i n cl u de a state m e nt t h at i n di cat es t he pr o d uct  is f or i n vesti gati o n al use  o nl y.  
 
5. 4. 3  St u d y  Dr u g  St ora ge  
A X T 1 0 7 is t o be st ore d at 2 -8º C, i n a sec urel y l oc k e d area wit h access gi ve n o nl y t o a p pr o priat e  
st u d y pers o n nel.  
 
5. 4. 4  A d diti o nal  Cli ni cal  S u p pli es  
Uri ne pre g na nc y test kits a n d cli nical la b or at or y s u p plies f or o btai ni n g bl o o d a n d uri ne  
s peci me ns will b e pr o vi de d b y t h e ce ntral  l a b orat or y. 
 
5. 4. 5  St u d y  Dr u g  Acc o u nt a bilit y  
It is t he res p o nsi bilit y of t he Pri nci pal I n v esti gat or ( or desi g nee) t o e ns ure t he re cei pt, 
acc o u nt a bilit y, pr o per st ora g e, a n d dis pe nsi n g of st u d y dr u g. I n ve nt or y pr oce d ures s h o ul d be i n  
place a n d c o n d ucte d u p o n rec ei pt of st u d y dr u g a n d s u p ple me ntal s u p plies (e. g., s yri n ges), a n d  
a n y discre pa n c y is t o be c o m m u ni cat e d t o t h e S p o ns or i m me diat el y u p o n a ware n ess b y t he  
Pri nci pal I n v esti gat or. T he cli nical s u p plies s hi p me nt f or m m ust be c o m pl ete d a n d a c o p y m ust  
be ret ur ne d t o t he S p o ns or as directe d, w hil e t h e ori gi nal re c or d is ret ai ne d i n t he cli ni cal trial  
files. A c urre nt r ec or d of t he i n ve nt or y, st or a ge c o n diti o ns, a n d dis pe nsi n g m ust be ke pt b y t he 
i n vesti gati ve site staff, a n d will b e pr o vi de d t o t he S p o ns or re prese ntati ves ( St u d y m o nit or) w he n 
necessar y f or t he p ur p ose of a cc o u nti n g f or all cli nic al s u p plies. A n y discre p a nc y a n d/ or  
defici e nc y  m ust be  rec or d e d wit h pr o vi d e d e x pl a nati o n. 
 
5. 4. 6  Ret ur n  of  U n use d  S u p pli es  
All u n use d s u p plies are t o be ret ur ne d t o t h e S p o ns or u p o n c o m pleti o n of t h e st u d y. It is t h e  
res p o nsi bilit y of t he Pri nci pal I n v esti gat or t o e ns ure t he pr o per pac ka gi n g a n d s hi p m e nt of 
cli ni cal s u p plies w he n ret ur ni n g t o t he S p o ns or. T he site’s sta n dar d pra cti ce will b e f oll o we d f or  
t he dis p osal  of use d st u d y dr u g s u p plies.  
 
5. 5  Assess me nt  of  S afet y  
5. 5. 1  Defi niti o ns  a n d classifi cati o n  of  A d verse  E ve nts  
A n a d verse e ve nt ( A E) is c o nsi d ere d as a n y u nt o war d me dic al oc c urre nce ass ociat e d wit h t h e use  
of a dr u g pr o d uct i n h u ma ns, w het her or n ot c o nsi der e d dr u g relate d. A n a d verse e v e nt (als o  
referre d t o as a n a d verse e x p erie n ce) ca n b e a n y u nfa v ora ble a n d u ni nte n d e d si g n (e. 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 te m p orall y ass ociat e d wit h t h e use of a dr u g,  
a n d d oes n ot i m pl y a n y j u d g me nt a b o ut c a usalit y. A n a d verse e ve nt ca n arise wit h a n y use of t he  
dr u g (e. g., off -la bel use, use 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 nistr ati o n,  f or m ulati o n, or d ose, i ncl u di n g a n o ver d ose.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 0  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
Life -t hre at e ni n g a dv erse eve nt or life-t hre ate ni n g s us pecte d a dv erse re acti o n: A n a d verse e ve nt 
or s us pecte d a d verse re acti o n is c o nsi der e d "life -t hre ate ni n g" if, i n t he vie w of eit h er t he 
I n vesti gat or or S p o ns or, its oc c urre nce plac es t he patie nt or s u bje ct at i m me di ate ris k of de at h. It 
d oes n ot i ncl u d e a n a d v erse e ve nt or s us pecte d a d v erse reacti o n t hat, ha d it occ urre d i n a m or e  
se vere f or m, mi g ht ha v e  ca use d  de at h.  
 
Seri o us a dverse eve nt or seri o us s us pecte d a dverse re acti o n : A n a d verse e ve nt or s us pecte d 
a d verse reacti o n is c o nsi d ere d "seri o us" if, i n t h e vie w of eit her t h e I n vesti g at or or s p o ns or, it  
res ults i n a n y of t he f oll o wi n g o utc o mes:  
 
•  Deat h  
•  a life-t hre ate ni n g a d verse e ve nt  
•  i n pati e nt h os pitalizati o n  or  pr ol o n gati o n  of  e xisti n g  h os pitali zati o n  
•  a persiste nt or si g nific a nt i n ca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d u ct  
n or mal  lif e f u ncti o ns 
•  a c o n ge nital a n o mal y/ birt h  defect  
 
I m p orta nt me di cal e ve nts t hat ma y n ot res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitali zati o n ma y b e c o nsi dere d seri o us w he n, base d u p o n a p pr o priate m e dical j u d g m e nt, t h e y  
ma y je o p ar diz e t he patie nt or s u bject a n d m a y re q uir e me di cal or s ur gi cal i nter ve nti o n t o pr e ve nt  
o ne of t he o ut c o mes liste d i n t his defi niti o n. E xa m pl es of s uc h me dic al e ve nts i ncl u d e aller gi c  
br o nc h os pas m re q uiri n g i nte nsi v e treat me nt i n a n e m er ge nc y r o o m or at h o me, bl o o d d yscrasias  
or c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt h os pitalizati o n, or t he d e vel o p me nt of dr u g  
de pe n de nc y  or  dr u g a b use.  
 
S us pecte d a dv erse re acti o n : A n y a d verse e ve nt f or w hic h t her e is a reas o na ble p ossi bilit y t h at 
t he dr u g ca use d t he a d verse e ve nt. F or t h e p ur p oses of I N D safet y re p orti n g, "reas o na bl e 
p ossi bilit y" me a ns t here is e vi de nc e t o s u g gest a ca usal relati o ns hi p bet wee n t he dr u g a n d t he 
a d verse e ve nt. S us pecte d a d v erse rea cti o n i m plies a l esser de gree of certai nt y a b o ut ca usalit y  
t ha n a d verse rea cti o n, w hi c h me a ns a n y a d verse e ve nt ca use d b y a  dr u g.  
 
U nex pect e d a dverse ev e nt or u nex p ect e d s us pecte d a dverse re acti o n : A n a d verse e ve nt or 
s us pecte d a d verse re acti o n is c o nsi der e d " u ne x pecte d" if it is n ot liste d i n t he I n vesti gat or  
br oc h ure or is n ot liste d at t he s pecificit y or se verit y t hat has be e n o bser ve d; or, if a n I n vesti g at or  
br oc h ure is n ot re q uire d or a vaila ble, is n ot c o nsiste nt wit h t he ris k i nf or mati o n descri be d i n t he  
ge neral i n vesti g ati o n al pla n or else w here i n t he c urre nt a p pli cati o n, as a m e n de d. F or e xa m ple,  
u n der t his defi niti o n, h e patic n ecr osis w o ul d be u n e x pecte d ( b y virt ue of gre ater se v erit y) if t he  
I n vesti gat or br o c h ure referr e d o nl y t o ele v ate d h e patic e nz y mes or he patitis. Si mil arl y, cer e bral 
t hr o m b oe m b olis m a n d cere bral vasc ulitis w o ul d be u ne x pect e d ( b y virt u e of great er s pecificit y) 
if t he I n vesti gat or br o c h ure list e d o nl y c ere bral vasc ular ac ci de nts. " U ne x pecte d," as use d i n t his 
defi niti o n, als o ref ers t o a d verse e v e nts or s us pecte d a d verse reacti o ns t hat are me nti o ne d i n t he  
I n vesti gat or br o c h ure as occ urri n g wit h a class of dru gs or as a ntici p ate d fr o m t he  
p har mac ol o gic al pr o perties of t he dr u g, b ut are n ot s pecifi call y me nti o ne d as oc c urri n g wit h t he  
partic ular  dr u g u n der i n v esti gati o n.  
 
5. 5. 2  C oll ecti o n  a n d Assess m e nt  of  A d verse  E ve nts  
I n t his st u d y, A Es are t o be c oll ecte d fr o m t he ti m e of i nf or me d c o nse nt. T heref or e, a n y 
u n desira ble  me dical  c o n diti o n  oc c urri n g  at a n y ti me, i ncl u di n g Baseli ne  or  pre -tre at m e nt peri o d  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 1  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
(e ve n if n o st u d y dr u g has be e n a d mi nistere d), m ust be e val u ate d f or a n A E. A n y cli ni call y 
si g nifica nt c ha n g e fr o m baseli ne i n a s u bject’s c o n diti o n or pre -e xisti n g c o n diti o n m ust b e  
e val uate d as a n A E, u nless t he c ha n g e is det er mi n e d t o be a c o nti n uati o n of a pre -e xisti n g  
c o n diti o n t hat is d oc u me nte d i n t he s u bject’s me di cal hist or y. H o we ver, a cli nicall y si g nifica nt  
w orse ni n g  i n se verit y, i nte nsit y, or  fre q ue nc y of  a pre -e xisti n g c o n diti o n  ma y  i n dic ate a n A E.  
 
All c o n diti o ns t hat lea d t o h os pitaliz ati o ns, defi ne d as a n o ver ni g ht h os pit al sta y, are t o be  
c o nsi dere d as S A Es. Ele cti v e s ur gical pr o ce d ures sc he d ule d or pl a n ne d pri or t o st u d y e ntr y t h at  
d o n ot re q uire o v er ni g ht h os pital st a y, a n d t he u n d erl yi n g dia g n osis f or w hic h s ur ger y is t o b e  
perf or me d  is ca pt ure d  i n t he m e dic al  hist or y  as  a pre -e xisti n g  c o n diti o n  are n ot  c o nsi der e d  A Es.  
T he s ur gical pr oce d ure s h o ul d still b e d oc u m e nte d i n t he s u bject rec or ds wit h a n e x pla n ati o n of  
circ u mst a nces.  
 
Lac k  of  effic ac y  of  A X T 1 0 7  f or t he c o n diti o n  bei n g  i n vesti gat e d is n ot  c o nsi dere d  a n A E  u nl ess  a 
cli ni call y  si g nific a nt c h a n ge is assesse d  b y t he Pri nci pal  I n vesti gat or. 
 
A d verse e ve nts i n t his st u d y will be c oll ecte d b y wa y of see ki n g i nf or m ati o n ( direct q u esti o ni n g  
a n d p h ysical e xa mi nati o n) b y t he I n vesti gat or at e ac h s u bject c o ntact, or u p o n i nf or mati o n t h at is  
pr o vi de d v ol u nt aril y b y t he s u bje ct, a n d ar e t o be f oll o we d t o res ol uti o n, or u ntil t he c o n diti o n is  
deter mi ne d t o b e irre versi ble, c hr o nic, or sta ble, f or u p t o 3 0 da ys after t he s u bje ct’s e xit fr o m t he  
st u d y. U nres ol ve d A Es be y o n d 3 0 da ys of t he s u bject’s e xit fr o m t he st u d y s h o ul d be e val u ate d  
o n a case -b y -case b asis, de pe n di n g u p o n t he c o n diti o n a n d base d o n t he cli nical j u d ge m e nt of t h e  
I n vesti gat or or at  t he dir ecti o n of t he S p o ns or.  
 
A d verse e ve nts will b e assesse d b y t he I n vesti g at or f or seri o us ness (see C F R 2 1 part 3 1 2 crit eria  
i n Secti o n 6. 5. 1) a n d se v erit y  a cc or di n g t o t he  f oll o wi n g criteria:  
 
Mil d: N o i nterf ere nce wit h t he s u bj ect’s dail y a cti vities; n o me dical i nt er ve nti o n/t her a p y  
re q uire d 
 
M o der ate: P ossi ble i nterfere n ce wit h t he s u bje ct’s d ail y a cti viti es; n o or mi ni mal  
me dic al  i nt er ve nti o n/t h era p y re q uire d 
 
Se vere: C o nsi der a ble i nterfer e nce wit h t he s u bj ect’s dail y a cti viti es; me dical  
i nter ve nti o n/t hera p y re q uir e d 
 
T he  I n vesti gat or m ust  als o ma ke  a deter mi nati o n  of  relat e d ness t o t he st u d y dr u g  (relate d or  n ot  
relat e d), base d o n t he I n v esti gat or’s cli nical j u d g m e nt, facts ( pr o d uct i nf or m ati o n or 
I n vesti gat or’s Br oc h ur e), e vi de n ce, a n d scie ntific r ati o nales as t o w het h er t here is a ca usal 
relati o ns hi p bet wee n t h e  A E  a n d A X T 1 0 7.  
 
•  A n A E m ust be re p ort e d as Rel at e d t o A X T 1 0 7 if t h ere is a r eas o na ble p ossi bilit y t hat t h e  
e x perie n ce m a y ha ve b ee n c a use d b y A X T 1 0 7, a n d t he A E ca n n ot b e rea dil y e x plai n e d b y  
t he s u bject’s cli nic al stat e, c o nc urr e nt ill ness, or c o nc o mit a nt t her a pies. 
•  A n A E ma y be c o nsi der e d as N ot Rel ate d t o A X T 1 0 7 if e vi de n ce t h at t he A E h as a n 
eti ol o g y ot her t h a n t he A X T 1 0 7 (e. g., pre -e xisti n g m e dical c o n diti o n, u n derl yi n g disease,  
c o nc urre nt ill n ess, or c o nc o mit a nt m e dic ati o n); a n d/ or t he A E has n o pla usi ble t e m p oral  
relati o ns hi p t o a d mi nistr ati o n of t he A X T 1 0 7 (e. g., n e wl y dia g n ose d c o n diti o n after 
a d mi nistr ati o n  of A X T 1 0 7).  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 2  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
T he  I n vesti gat or will  be  re q uir e d t o assess  t he o utc o me  of  t he A E  as o ne of  t he f oll o wi n g: 
• Res ol ve d  
• Res ol ve d  wit h  se q uelae 
• Res ol vi n g  
• N ot  Res ol ve d  
• Fat al  
• U n k n o w n  
A n e ve nt t hat is assesse d as res ol ve d wit h se q uelae or res ol vi n g i n di cat es t hat t he s u bject has 
sta bili ze d t o a le v el ac ce pt a ble t o t he I n vesti g at or a n d has  c o nc urre nce  b y  t he S p o ns or.  
 
5. 5. 3  Re p orti n g  of  A d verse  E ve nts  
All A Es re p orte d after t he s u bj ects has pr o vi d e d writte n i nf or m e d c o nse nt a n d wit hi n 3 0 da ys 
f oll o wi n g t he l ast visit  will  be  rec or de d i n t he s u bject’s me dical  rec or ds a n d t he a p pr o priat e C R F.  
 
Rec o g niz e d me dical ter ms s h o ul d be use d w he n r ec or di n g t he A E, a v oi di n g c oll o q ui alis ms  
a n d/ or  a b bre viati o ns  w he n  p ossi ble.  Se parat e  A Es  s h o ul d be  re p orte d f or e ve nts  t hat are 
o bser ve d si m ult a ne o usl y b ut are dee me d t o b e u nrel ate d base d o n t h e cli nical j u d ge me nt of t he  
I n vesti gat or. If a di a g n osis  ca n n ot be  esta blis he d,  t he pr o mi ne nt  si g n, s y m pt o m, or  fi n di n g 
s h o ul d be d oc u me nte d as t h e A E descri pti o n. I nter mitte nt e ve nts s h o ul d be r e p orte d wit h t he date  
of t he first e pis o de as t he o nset date, a n d wit h m a xi m u m se verit y as o bser ve d a m o n g t he  
c olle cti v e e pis o des. I nter mitte nt h os pitalizati o ns as a res ult of a pri mar y e ve nt s h o ul d be  
d oc u me nt e d  wit h t he pri mar y e v e nt  a n d n ot as se par ate e ve nts.  
 
Seri o us  E ve nts  Re p orti n g  Criteria  
Seri o us A Es m ust be re p orte d t o t he S p o ns or or S p o ns or re prese ntati ve wit hi n 2 4 h o urs of t he  
I n vesti gat or’s k n o wle d g e of t he e v e nt. A n S A E re p ort f or m, i ncl u di n g at mi ni m u m s u bj ect 
i de ntificati o n, A E descri pti o n, a n d o nset dat e m ust b e f or war de d t o t h e S p o ns or or S p o ns or 
re prese ntati ve at t he f oll o wi n g n u m b er/e mail:  
 
E mail: safet y gr o u p @cli ni pa ce.c o m 
S A E  Fa x  : 1-9 1 9 -5 7 3 -0 3 3 2  
 
U p o n a vaila bilit y of a n y ne w i nf or m ati o n, t he s u bje ct’s me dic al re c or ds a n d C R Fs m ust b e  
u p date d,  a n d t he i nf or mati o n is t o be pr o vi d e d  t o t he S p o ns or w he n  a p plica ble.  
 
5. 5. 4  A d diti o nal  Safet y  Assess m e nts  
Refer  t o t h e M O P  f or a descri pti o n  of  t he f oll o wi n g pr oce d ures  t o be  perf or m e d  i n t h e st u d y. 
 
Best  C orrecte d  Vis ual  A c uit y  
B C V A will be meas ure d i n b ot h e y es starti n g at Scre e ni n g ( Da y -1 4 t o Da y -1) a n d at all  
atte n d e d visits, usi n g a n E T D R S c hart, wit h t he use of sta n dar diz e d ma nifest refra cti o n a n d  
testi n g pr ot oc ol  as  descri be d  i n t he Ma n ual  of  Pr oce d ure.  B C V A  e val uati o n  s h o ul d prece d e  a n y  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 3  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
st u d y pr oce d ure t h at re q uires c o nta ct wit h t he e y e. All e xa mi ners m ust b e certifie d pri or t o t h e  
Scree ni n g  visit.  
 
I ntra oc ular Press ure  
I O P will be meas ure d i n eac h e ye at Scree ni n g ( Da y -1 4 t o Da y -1), bef ore a n d after i njecti o n at  
Baseli ne ( Da y 0), a n d at all ot h er atte n de d visits pri or t o p u pil dilati o n. T he sa me t y p e of  
t o n o met er s h o ul d be use d t hr o u g h o ut t he st u d y f or t h e sa me s u bje ct. At t h e Baseli ne visit, 
t o n o metr y will be p erf or me d pri or t o a d mi nistrati o n of A X T 1 0 7 a n d will be re p eate d at 3 0 ( ± 1 0) 
mi n utes p ost -i njecti o n of A X T 1 0 7. El e vate d I O P of ≥ 3 0 m m H g will b e re-m eas ure d at 6 0 ( ± 1 0)  
mi n utes  p ost  i nj ecti o n of A X T 1 0 7.  
 
Slit  La m p  Bi o micr osc o p y  
Slit  l a m p bi o micr osc o p y  will  be  perf or me d  o n  eac h e ye starti n g at Scree ni n g  ( Da y -1 4  t o Da y  -1)  
a n d at all atte n d e d visits. Assess me nt of t he e y eli ds, c o nj u ncti va, c or n ea, a nt eri or c h a m ber, iris,  
a n d le ns will b e d oc u m e nte d. At t he Baseli ne visit, t he bi o mi cr osc o p y e xa mi nati o n will be  
perf or me d  pri or  t o a d mi nistr ati o n of A X T 1 0 7.  
 
Dilate d  F u n d us  E xa mi nati o n  
D F E will b e perf or m e d o n eac h e ye at Scree ni n g ( Da y -1 4 t o Da y -1), bef ore a n d after st u d y  
dr u g i njecti o n at Baseli ne ( Da y 0), a n d at all ot her att e n de d visits t o assess c ha n ge fr o m baseli ne  
a n d t he visi bilit y of A X T 1 0 7. Assess me nts of t he vitre o us, reti na, mac ula, c h or oi d, o ptic n er ve,  
a n d c u p/ disc r ati o will be d o c u me nt e d.. A d diti o n al f oll o w -u p visits ma y b e re q uir e d t o e val uat e  
t he A X T 1 0 7 visi bilit y  if A X T 1 0 7 is  still visi ble at Visit 1 5/ E xit  ( Wee k 4 8). 
 
S pectral  D o mai n  O ptical  C o here nce  T o m o gra p h y  
S D -O C T i ma ges will be ca pt ur e d f or eac h e ye starti n g at Scree ni n g ( Da y -1 4 t o Da y -1) a n d at  
all atte n d e d visits, f oll o wi n g t he st a n dar diz e d pr oce d ures detaile d i n t he Rea di n g Ce nt er Ma n ual.  
T he  a p pr o ve d e q ui p me nt  is als o liste d i n t he Re a di n g Ce nter Ma n ual.  
 
F u n d us  P h ot o gra p h y  
F u n d us  p h ot o gra p h y  of  eac h e ye is t o b e o btai ne d  at Scree ni n g  ( Da y -1 4  t o Da y  -1),  
Visit 6 ( Wee k 1 2), Visit 9 ( Wee k 2 4), a n d Visit 1 5/ E xit ( We e k 4 8). Refer t o t he Re a di n g Ce nter  
Ma n ual  f or t he pr oc e d ure t o o btai n c ol or F P. 
 
Fl u orescei n  A n gi o gra p h y  
Fl u oresc ei n  a n gi o gra p h y  of  eac h  e y e will  be  o bt ai ne d  at Scree ni n g  ( Da y -1 4  t o Da y  -1),  
Visit 6 ( Wee k 1 2), Visit 9 ( Wee k 2 4) a n d Visit 1 5/ E xit ( We e k 4 8). S o di u m fl u or escei n will be  
i njecte d i nt o s yste mi c cir c ulati o n a n d di gital i m a ges of t he reti na will be t a ke n wit h bl u e li g ht 
ill u mi nati o n at 4 9 0  n m  of  wa vel e n gt h.  Refer  t o t h e Rea di n g  Ce nter  Ma n ual  f or t he pr oce d ure.  
 
O ptical  C o here nce  T o m o gra p h y  A n gi o gra p h y  
O C T -A i ma ges will b e ca pt ure d at selecte d sit es o nl y. I ma ges will b e ta k e n f or eac h e ye starti n g  
at Scree ni n g ( D a y -1 4 t o Da y -1) a n d at all atte n de d visits, a n d will f oll o w sta n dar dize d  
pr oce d ures  as detaile d  i n t he R ea di n g Ce nter Ma n ual.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 4  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
Wi defiel d  Reti nal  I m a gi n g ( O pt os) 
Wi defi el d reti nal i ma g e will b e use d t o c a pt ure t he A X T 1 0 7 visi bilit y i n t h e st u d y e ye at  
Baseli ne  ( Da y 0) aft er  A X T 1 0 7 i njecti o n,  We e k  8,  a n d Wee k  3 6  at sele cte d  sit es. 
 
A C  Ta p  
A nteri or c ha m ber para ce nt esis will be p erf or me d at s electe d sit es at Baseli ne ( Da y 0),  
Visit  4  ( Wee k 4),  Visit 6  ( W ee k 1 2), Visit 9  ( We e k 2 4),  a n d Visit 1 4  ( Wee k 4 4).  
 
O ptical  C o here nc e  T o m o gra p h y  I ma gi n g at H o m e  
H o me O C T i ma gi n g will b e perf or me d we e kl y f or e ac h e ye usi n g t he N otal Visi o n H o me O C T  
de vice  b y st u d y s u bje cts, aft er e nr oll me nt  at sel ect e d sites.  
 
Vis ual  A c uit y  Meas ure me nt  at H o m e  
Vis ual ac uit y me as ure me nt will be p erf or me d we e kl y f or eac h e ye, utilizi n g t he M & S  
Tec h n ol o g y  vis ual  ac uit y s yste m at h o me  b y  st u d y s u bjects, aft er e nr oll me nt at sel ect e d sites. 
 
La b orat or y  E val uati o n  
La b orat or y tests (fasti n g f or dia betic s u bje cts) will i n cl u de a c o m pl ete bl o o d c o u nt ( he mat ol o g y  
a n d differe ntial), c he mistr y pa nel, a n d uri n al ysis at S cree ni n g ( Da y -1 4 t o Da y -1), Visit 9 ( We e k  
2 4), a n d Visit 1 5 ( We e k 4 8). T he Scre e ni n g cli ni cal l a b orat or y res ults m ust be re vie we d pri or t o  
e nr oll m e nt t o i d e ntif y a n y cli nicall y  si g nifi ca nt disease  t hat i n t h e o pi ni o n of  t he I n v esti gat or 
ma y  pre cl u de  t h e s u bject fr o m partici pati o n  i n t h e st u d y. A n  a nti-dr u g  a nti b o d y  ( A D A) assa y  
will be c o m plete d at Scree ni n g, Visit 4 ( We e k 4), Visit 6 ( Wee k 1 2), a n d Visit 1 5 ( We e k  
4 8/ E xit).  
 
Vital  Si g ns  
Heart rat e a n d bl o o d press ure will be m eas ure d starti n g at Scree ni n g ( Da y -1 4 t o Da y -1) a n d at  
all atte n d e d visits, usi n g a n a ut o m ate d or m a n ual bl o o d press ure m o nit or. S yst oli c a n d di ast oli c  
bl o o d press ures will be re c or de d i n milli meters of m erc ur y ( m m H g), a n d he art rate will be  
rec or de d i n beats per mi n ute ( b p m).  
 
P h ysical  E xa mi nati o n  
A  c o m plete p h ysical  e xa mi nati o n  will  be  c o n d ucte d  b y  t he Pri nci pal  I n vesti gat or or  desi g ne e  at 
Scree ni n g  ( Da y -1 4 t o  Da y -1).  
 
Pre g na nc y  
W o me n of c hil d be ari n g p ote ntial are n ot e xcl u de d fr o m t he st u d y as l o n g as it c a n be deter mi n e d  
at Baseli ne t h at t h e y are n ot pr e g na nt, n ursi n g, or pla n ni n g a pre g na n c y, a n d are usi n g effecti ve  
met h o ds  of  c o ntrac e pti o n. Effecti ve  c o ntrac e pti o n  m et h o ds  i ncl u de: 
 
•  T otal a bsti ne n ce ( w he n t his is i n li n e wit h t he pr eferr e d a n d us ual lifest yl e of t he s u bje ct).  
Peri o dic a bsti ne nc e (e. g., cale n dar, o v ulati o n, s y m pt ot her mal, p ost -o v ulati o n m et h o ds) a n d  
wit h dra wal  are n ot acce pta bl e met h o ds of c o ntrac e pti o n  
•  Fe m ale  st erilizati o n ( h a ve ha d  s ur gical bilat eral  o o p h orect o m y  wit h  or  wit h o ut  h ystere ct o m y)  
or  t u bal li g ati o n at l east 6  wee ks  bef or e  Baseli n e.  I n case of  o o p h orect o m y  al o n e, o nl y  w he n  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 5  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
t he re pr o d ucti ve st at us of t he w o ma n h as bee n c o nfir me d b y f oll o w u p h or m o n e le v el 
assess me nt 
•  Male steriliz ati o n ( at le ast 6 m o nt hs pri or t o Baseli ne). F or fe m ale s u bj ects i n t he st u d y, t h e  
vasect o mize d  m ale p art ner s h o ul d  be  t h e s ole part ner f or t hat  s u bject 
•  Barrier m et h o ds of c o ntra ce pti o n: c o n d o m or occl usi ve ca p ( di a p hra g m or c er vic al/ v a ult  
ca ps)  wit h  s per mici d al f oa m/ gel/fil m/ crea m/ va gi n al s u p p osit or y 
•  Use of oral, i nje cte d or i m pl a nte d h or m o nal met h o ds of c o ntrac e pti o n or ot her f or ms of  
h or m o nal c o ntrac e pti o n t hat ha v e c o m p ara bl e effi ca c y (fail ur e rate < 1 %), f or e xa m ple  
h or m o ne  va gi nal  ri n g or tra ns der mal h or m o n e c o ntr a ce pti o n  
•  Place m e nt  of  a n i ntr a uteri ne de vi ce  (I U D) or  i ntra uteri ne s yste m (I U S) 
 
Pre g na nc y is n ot c o nsi d ere d a n A E, b ut m ust be re p orte d if oc c urre d d uri n g a cli nical st u d y.  
Fe m ale s u bj ects m ust b e i nstr ucte d t o c o ntact t he I n v esti gat or i m m e diatel y if pre g na nc y is  
s us pecte d d uri n g t h eir partici p ati o n i n t he st u d y. E ver y atte m pt will be m a de t o c olle ct data o n  
t he pre g na n c y of fe male s u bje cts a n d/ or pr e g na nt p art ners of mal e s u bjects. Decisi o n re gar di n g 
c o nti n uati o n of t h e s u bject i n t h e st u d y will b e ma de base d u p o n t he circ u mst a nces s urr o u n di n g  
t he pre g na nc y.  Pre g na n c y  m ust  be  f oll o we d t o t er m t o assess  f or p ote ntial  c o m plicati o ns.  
C o m plic ati o ns  ma y  be  re p orta ble base d  o n  cli nic al j u d ge me nt. 
 
5. 6  Assess me nt  of  Effic ac y  
5. 6. 1  Ce ntral  S u bfi el d  T hi c k ness  
S D -O C T  will  be  perf or me d  f or b ot h  e yes  starti n g at Scree ni n g  ( Da y -1 4  t o Da y -1)  a n d at all 
atte n d e d  visits. Mea n  c ha n g e i n  C S T  fr o m Baseli ne ( Da y  0)  will  be assesse d.  
 
5. 6. 2  Best  C orrect e d  Vis ual  Ac uit y  
Mea n c ha n ge i n E T D R S letters fr o m Baseli ne ( Da y 0) a n d perce nta ges i m pr o vi n g at least 5, 1 0,  
a n d 1 5 lett ers will be  assesse d.  
 
5. 7  C o nti n ge nc y  Me as ures  i n C ase  of  a  Gl o b al  E mer ge nc y  
I n case of gl o bal or re gi o nal e m er ge ncies, s uc h as t h e C o vi d-1 9 p u bli c healt h e mer ge nc y, t he  
i n vesti gati o nal site ma y i m ple me nt c o nti n ge n c y pla ns t o mi ni mize t he i m pact of t he e mer ge n c y 
o n trial i nte grit y a n d t o re d uce missi n g dat a, w hile e ns uri n g t he safet y of st u d y p arti ci pa nts a n d  
t he i n vesti gati o nal site staff. I n t he e ve nt t hat st u d y p artici pa nts ar e u na ble or u n willi n g t o atte n d 
i n pers o n st u d y visits, tele p h o ne a n d virt u al visits ma y be c o n d uct e d f or c o m pleti o n of 
assess me nts t hat c a n be c o n d ucte d wit h o ut re q uiri n g a n i n -pers o n e val uati o n b y t he st u d y  
i n vesti gat or (e g, i n-h o me assess me nts of O C T a n d V A, s u bject re p ort e d s y m pt o m ol o g y a n d  
A Es). Virt ual or tele p h o ne visits s h o ul d be clearl y d o c u me nt e d as s uc h i n t h e case re p ort f or ms  
t o acc o u nt f or missi n g  safet y a n d effica c y assess me nt  w he n s u m mariz e d.  
 
De viati o ns fr o m t he pr ot o c ol m a y be u na v oi d a ble d uri n g t he c urr e nt C o vi d -1 9 p u blic he alt h  
e mer ge n c y. Dela ye d or misse d visits d ue C O VI D -1 9 ill ness a n d/ or C O VI D -1 9 c o ntr ol meas ures  
s h o ul d be d oc u me nte d as s uc h i n a n eff ort t o assess t he p ote ntial i m pa ct of C o vi d -1 9 o n st u d y  
c o n d uct a n d t he c oll ecti o n of data. 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 6  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
6.  S T A TI S TI C A L  A N A L Y SI S  P L A N  
6. 1  A n al ysis  P o p ul ati o ns  
I nte nt-t o-Treat  (I T T) P o p ul ati o n:  
 
T he I T T p o p ulati o n will i ncl u d e all s u bjects w h o ha v e recei ve d st u d y m e dicati o n. T his  
p o p ulati o n  will  be  t h e pri mar y  p o p ul ati o n  f or effic ac y  a nal yses  a n d will  be  use d  t o s u m mariz e all 
effica c y  varia bles.  
 
Safet y  P o p ulati o n:  
 
T he safet y p o p ulati o n will i ncl u d e all s u bj ects w h o h a ve rec ei ve d st u d y me dic ati o n. T his  
p o p ulati o n  will  be  use d  t o s u m mariz e safet y vari a bles  a n d will  s u m marize s u bje cts as  tre ate d. 
 
6. 2  St atisti c al  H y p ot heses  
N o  statistical h y p ot heses  ar e defi ne d  f or t his st u d y. 
 
6. 3  St atisti c al  Met h o ds  
A ge, se x, race, et h nicit y, a n d baseli ne assess me nts will be s u m m ariz e d a n d list e d b y d ose le vel.  
Me dical hist or y, hist or y of oc ular s ur ger y a n d pr o ce d ures, a n d c o nc o mita nt me dicati o n will als o  
be  s u m mariz e d a n d liste d. 
 
C ha n ges fr o m baseli ne i n B C V A a n d reti nal t hic k n ess ( C S T) will be s u m marize d b y d ose le vel  
usi n g c o nti n u o us s u m mar y st atistics. B C V A c ha n ge will be s u m m ariz e d usi n g cate g oric al  
s u m maries as  well,  i ncl u di n g fre q ue nc y c o u nts  a n d perce nt a ges  i m pr o vi n g at le ast 5,  1 0,  a n d 1 5  
lett ers. 
 
Ver bati m d escri pti o ns of A Es will be ma p p e d t o Me d D R A t hesa ur us ter ms a n d be prese nt e d i n a  
data listi n g. Tr eat me nt e mer ge nt A Es, t h ose t hat occ ur after t h e first d ose of st u d y me dicati o n,  
will be s u m m ariz e d b y d ose le vel usi n g fre q ue n c y a n d perce nt f or eac h s yste m or g a n cl ass  
( S O C) a n d preferre d ter m ( P T) wit hi n e ac h S O C. S u m mari es will be pr ese nte d se par atel y f or  
oc ular  a n d n o n -oc ular  A Es.  T E A Es will  be  s u m mari ze d b y  se verit y a n d st u d y dr u g  relate d ness. 
 
B C V A will be s u m mari ze d at eac h ti m e p oi nt usi n g b ot h c o nti n u o us s u m m aries ( E T D R S lett er  
sc ore), i ncl u di n g c ha n ge fr o m Baseli ne ( Da y 0), a n d cate g orical s u m mari es, i ncl u di n g c ha n g e  
fr o m Baseli ne ( Da y 0) o n a n  E T D R S c hart  i n t he n u m ber  of  li nes. 
 
I O P will be s u m mari ze d at ea c h ti me p oi nt usi n g b ot h c o nti n u o us s u m maries, i ncl u di n g c h a n ge 
fr o m Baseli ne  ( Da y 0),  a n d c ate g orical  s u m maries f or pre -state d cate g ories  of  c ha n ge i n I O P. 
 
Slit la m p bi o micr osc o p y a n d o p ht hal m osc o p y me as ures will be s u m m ariz e d at e ac h m eas ure d  
ti me p oi nt usi n g cate g ori cal  s u m m ar y statistics. 
 
F A  will  be s u m marize d  b y  visit.  
 
D R S S  will  be  s u m mari ze d b y  visit  a n d c ha n ge fr o m Baseli ne  ( Da y 0)  t o eac h visit.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 7  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
Vital si g ns will b e s u m marize d at ea c h visit a n d f or c ha n ge fr o m Baseli ne ( Da y 0) t o eac h visit  
usi n g  c o nti n u o us s u m mar y statisti cs  b y  treat me nt gr o u p a n d visit.  
 
Cli nic al l a b orat or y r es ults will b e s u m mari ze d usi n g b ot h c o nti n u o us s u m m aries, i n cl u di n g  
c ha n ge fr o m B aseli n e ( Da y 0), a n d discrete s u m m ari es, i ncl u di n g fr e q ue nc y a n d p erce nt of  
s u bjects wit h a n a b n or mal val ue a n d s hift t a bles fr o m Baseli n e ( Da y 0). A d diti o n all y, la b orat or y  
data  will b e  prese nte d i n  data listi n gs.  
 
E x pl orat or y a nal yses will be perf or m e d t o s u m m ariz e t he res ults o btai n e d fr o m t he N ot al Visi o n  
H o me  O C T  de vic e a n d  h o me M & S ®  T ec h n ol o g y  vis ual  ac uit y meas ure me nt.  
6. 4  S a m ple  Size  Det er mi n ati o n  
A p pr o xi matel y 1 8 s u bjects will be e nr oll e d, wit h 6 s u bjects i n eac h treat me nt gr o u p. T he fi nal  
n u m ber of s u bjects e nr olle d m a y be a dj uste d b ase d o n t he prese nc e of d ose li miti n g t o xicities.  
T his  sa m ple siz e is n ot pla n ne d b ase d  o n statistical  c o nsi derati o ns.  
 
6. 5  H a n dli n g  of  Missi n g  D at a  
F or  safet y me as ures,  missi n g  sc ores will  n ot  be  i m p ute d f or dat a  s u m mari es. 
C o m plet el y or partiall y missi n g o nset a n d res ol uti o n dates f or A Es a n d c o m pletel y or partiall y  
missi n g start a n d e n d dat es of c o nc o mita nt me di cati o ns will be i m p ute d i n a c o nser vati ve  
fas hi o n. F or bi o acti vit y e n d p oi nts, missi n g p ost-treat me nt val ues will b e i m p ute d usi n g t h e 
last-o bser vati o n -carri e d -f or w ar d ( L O C F) a p pr o ac h. 
 
6. 6  I nteri m A n al yses  
I nteri m a nal yses will be perf or m e d aft er all s u bjects c o m plete t h e Wee k 1 2, Wee k 2 4, a n d We e k 
3 6  visits t o e val u ate t he  o verall safet y  a n d preli mi n ar y  bi oacti vit y.  
 
7.  D A T A  M A N A G E M E N T  A N D  A D MI NI S T R A TI V E  R E Q UI R E M E N T S  
7. 1  C o m pleti o n  of  S o urce  D oc u me nt  a n d  C ase  Re p ort  F or ms  
T he nat ur e a n d l o cati o n of s o urc e d oc u m e ntati o n i n t his st u d y will be i d e ntifie d t o e ns ure t hat 
ori gi nal  dat a  re q uire d t o c o m plete t he C R Fs  e xist, are accessi ble,  a n d verifia ble  b y  t he S p o ns or  
or its re prese nt ati v es (e. g., st u d y m o nit or). A ut h ors of t he s o urce d oc u me nts a n d C R Fs m ust be  
i de ntifia bl e via t he st u d y pers o n nel l o g, a n d t h e i de ntit y of st u d y pers o n nel i m pl e me nti n g a n y  
m o dific ati o ns t o t he s o urce d o c u me nts a n d C R Fs m ust be d oc u me nte d (i e, b y i nitials or si g nat ure  
a n d date). A n y discr e pa nci es bet wee n t he s o urce d o c u me nts a n d C R Fs will be e xa mi ne d,  
c orrect e d, a n d a n e x pla nati o n will be pr o vi d e d i n writi n g. All m o dific ati o ns t o s o urc e dat a a n d  
C R Fs  will be c o m plete d  i n a m a n ner t hat d oes n ot o bsc ure t he  ori gi n al  e ntr y.  
 
De viati o ns fr o m t he pr ot o c ol, i n cl u di n g b ut n ot li mit e d t o a d her e nce t o eli gi bilit y criteria, st u d y  
c o n d uct, c o m pleti o n of safet y a n d effi cac y pr o ce d ures, visit wi n d o ws, st u d y dr u g a d mi nistrati o n,  
a n d data c oll ecti o n, m ust be d oc u me nt e d a n d e x plai n e d i n t he s o urc e d oc u m e nts, i ncl u di n g t he  
visit/ date of de viati o n, nat ur e of de viati o n, a n d a n y c orrecti v e acti o n ta k e n b y t he site if  
necessar y.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 8  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
7. 2  Q u alit y  C o ntr ol  a n d  Q u alit y  Ass ur a nce  
I nstr ucti o ns o n t he c o n d uct of t he pr ot oc ol, t he c o m pleti o n of s o urc e d oc u m e nts a n d C R Fs, a n d 
perf or ma nc e of t he st u d y pr oc e d ures will b e pr o vi de d t o t he I n vesti gat or. St u d y pr o gr ess will be  
m o nit ore d ( via m o nit ori n g visits) b y o n -site, writte n, re m ote r e vie w, or tele p h o ne 
c o m m u ni cati o ns bet wee n t he I n vesti g at or’s site st u d y staff a n d t he st u d y m o nit or ( or ot her  
S p o ns or re prese ntati v es). S o urce data v erifi cati o n of t he C R Fs a g ai nst ori gi nal s o urc e  
d oc u me nt ati o n a n d t he s u bj ect’s me dical rec or ds a n d ot her rec or ds rele va nt t o t he st u d y will be  
perf or me d d uri n g t he o n -sit e a n d/ or t ele p h o n e m o nit ori n g visits. All st u d y relat e d dat a i ncl u di n g  
C R Fs, me di cal r ec or ds (s o urce d oc u m e nts), si g ne d c o nse nt f or ms, st u d y relate d c orres p o n de n ce  
a n d re g ulat or y fil es, as well as, rec or ds of st u d y m e dicati o n st ora ge, pr e parati o n, a n d dis p ositi o n  
will  be  i ns pecte d d uri n g m o nit ori n g  visits.  
 
Data rec ei ve d vi a C R Fs will be re vie we d b y t h e S p o ns or f or acc urac y a n d c o m pl eti o n, a n d a n y  
discre pa ncies or s us pecte d err or i n t he d ata will be q uerie d b y t h e m o nit or a n d/ or S p o ns or ( or  
desi g nee).  
 
N o nc o m plia n ce wit h t he pr ot oc ol, S O Ps, G C P, a n d/ or a p plic a ble r e g ulat or y r e q uire me nt(s) t h at  
si g nifica ntl y aff ects or has t he p ote ntial t o si g nifi ca ntl y affect h u ma n s u bj ect pr ot ecti o n or  
relia bilit y of tri al res ults, will i nsti gat e a r o ot c a use a nal ysis a n d a p pr o pri ate c orrecti ve a n d 
pre ve nti v e acti o ns will b e i m ple me nte d b y t h e S p o ns or. Seri o us a n d/ or persiste nt n o nc o m plia nc e  
o n t he part of a n I n vesti g at or/i nstit uti o n, ma y lea d t o ter mi n ati o n of t he  
I n vesti gat or's/i nstit uti o n’s partici pati o n i n t h e  trial. 
 
7. 3  D at a  H a n dli n g  a n d  Rec or d  K ee pi n g  
A data ma n a ge m e nt pla n d etaili n g t he rele va nt as pects of data pr oc essi n g, i ncl u di n g st ora ge,  
vali dati o n, re c o nciliati o n, a n d releasi n g met h o ds, will be mai ntai ne d b y Ascle pi X. C o di n g of t he  
safet y para meters (e. g., A Es, e x a mi n ati o n fi n di n gs, me dic ati o n, me di cal hist or y) will be  
i m ple me nt e d usi n g a c urre nt  acc e pte d me di cal  di cti o nar y.  
 
8.  E T HI C S  
8. 1  Et hics  Re vi e w  
Pri or t o i nitiati o n of t he st u d y, t he pr ot o c ol, I C F, a n y materials use d t o r ecr uit s u bjects, a n d all  
d oc u me nts t h at ar e pr o vi de d t o s u bjects m ust u n d er g o re vie w b y a l o cal or c e ntral I R B, a n d  
d oc u me nt e d a p pr o val or fa v ora bl e o pi ni o n of t he I R B/I E C m ust be pr ese nt. O nl y t h e c urre nt  
I R B/I E C a p pr o ve d pr ot oc ol a n d st u d y materials m ust be use d uri n g t h e c o n d uct of t he st u d y. 
De viati o ns fr o m, or c ha n ges t o t he pr ot oc ol are pr o hi bite d wit h o ut a gre e me nt b y t he S p o ns or a n d  
wit h o ut d oc u m e nte d writte n I R B/I E C a p pr o val/fa v or a ble o pi ni o n of a n a p pr o priate a me n d me nt,  
e xce pt w he n n ecessar y t o eli mi nat e i m me di ate h azar ds t o t he s u bjects or w he n t he c h a n ge(s)  
i n v ol ves o nl y l o gistic al or a d mi nistr ati v e as pects of t he trial (e. g., c h a n ge of m o nit or(s), 
tele p h o n e n u m ber(s)). It is t he res p o nsi bilit y of t h e Pri nci pal I n vesti g at or t o a d here t o I R B/I E C 
re q uire m e nts wit h res pect t o pr o gress re p orts a n d n otificati o ns of a n y re p orta ble seri o us a d verse 
dr u g  reacti o ns pr o d uct. 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  2 9  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
8. 2  Et hic al  C o n d uct  of  St u d y  
T his cli nical st u d y m ust be c o n d uct e d i n ac c or da nc e wit h t he et hic al pri n ci pl es t hat ha v e t heir  
ori gi n i n t h e Decl arati o n of H elsi n ki, I C H g ui deli nes o utli ni n g G C P, a n d t h e I R B/I E C a n d  
a p plic a ble re g ul at or y re q uire m e nts. 
 
8. 3  I nf or m e d C o nse nt  a n d  S u bject  C o nfi de nti alit y  
V ol u ntar y writt e n i nf or m e d c o nse nt m ust be o btai ne d fr o m e ver y s u bje ct pri or t o t he i niti ati o n of  
a n y st u d y -relate d acti vities. T h e I n vesti g at or m ust h a ve a defi n e d pr ocess f or o btai ni n g c o nse nt. 
S u bjects m ust be gi ve n a m ple ti m e t o rea d, u n d ersta n d, a n d as k q uesti o ns, i n or der t o c o nsi der  
v ol u ntar y partici pati o n. T he s u bje ct m ust i n dic ate v ol u ntar y c o nse nt b y pr o vi di n g a writt e n  
si g ne d a n d dat e d i nf or m e d c o nse nt f or m (I C F). A c o p y of t he si g ne d a n d d ate d I C F m ust b e  
pr o vi de d  t o t h e s u bject, a n d t he ori gi na l d o c u me nt m ust  be  file d i n t he s u bj ect’s st u d y rec or ds. 
 
T he I C F m ust me et all a p plic a ble l o cal la ws a n d be writte n i n la n g ua g e t hat t he s u bje ct  
u n dersta n ds. S u bjects m ust b e i nf or m e d t hat t heir partici p ati o n i n t he st u d y is v ol u ntar y a n d t hat  
t heir de cisi o n t o wit h dra w fr o m partici p ati o n at a n y ti me d uri n g t he st u d y will n ot i m pact a n y 
as pect of t h eir sta n d ar d care. S u bj ects will be pr o vi d e d wit h c o nt act i nf or mati o n f or t he  
a p pr o priat e i n di vi d uals s h o ul d q uesti o ns or c o ncer ns arise aft er si g ni n g t h e I C F d uri n g t he  
cli ni cal st u d y. 
 
S u bjects m ust als o be i nf or m e d t hat t heir rec or ds ma y be acc esse d b y a p pr o priat e a ut h oriti es a n d  
S p o ns or -desi g nate d pers o n nel. T he I n vesti g at or m ust e ns ure all pr o ce d ures a n d pra cti ces are i n  
place  t o pr otect t he pri v ac y a n d  t h e best i nt erest of t h e s u bject. 
 
9.  I N V E S TI G A T O R O B LI G A TI O N S  
T he Pri nci p al I n vesti gat or is res p o nsi ble t o e ns ure t h at all st u d y pers o n nel are q ualifie d a n d  
pr o perl y trai ne d t o p erf or m t heir assi g ne d t as ks d uri n g t he c o urse of t h e st u d y. A rec or d of all  
st u d y pers o n nel a n d t h eir res p o nsi bilities m ust be ret ai ne d wit h t he st u d y re g ulat or y files, a n d  
m ust  be  ke pt  u p date d t o  reflect t he r ol es of  st u d y staff d uri n g t he e ntire c o urse  of  t he st u d y. 
 
9. 1  Direct  Access  t o S o urce  D at a/ D oc u me nts  
T he I n vesti g at or m ust a gree t o pr o vi de dir ect acc ess t o all s o urc e dat a a n d cli nic al d oc u me nts  
pertai ni n g t o t h e st u d y, t o t h e S p o ns or a n d its re prese ntati v e (i.e., st u d y m o nit or) a n d t o all  
re g ulat or y b o di es (i.e., I R B/I E C, F D A).  
 
9. 2  Fi n a nci n g  a n d  I ns ur a nce 
T he Pri nci p al I n vesti gat or a n d all s u b -I n vesti gat ors will pr o vi de fi na ncial discl os ure i nf or m ati o n 
pri or t o partici p ati o n i n t he st u d y, a n d m ust a gre e t o n otif y t he S p o ns or pr o m ptl y of a n y re q uire d  
re visi o n t o t h eir fi n a nci al discl os ure stat us d uri n g t h e ter m of t his st u d y, a n n uall y, or at t he e n d 
of t he st u d y (if a p plic a ble). U p dat e d fi na n cial discl os ure i nf or mati o n m ust b e pr o vi de d u p o n t he  
S p o ns or’s  writte n re q uest f oll o wi n g c o m pleti o n of  t h e st u d y. 


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  3 0  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
 
9. 3  Rec or d  Ret e nti o n  
All esse ntial rec or ds relati n g t o t he c o n d uct of t his st u d y m ust be ret ai ne d b y t he Pri nci pal  
I n vesti gat or u ntil  n otifie d b y  t he S p o ns or of  pr oce d ures t o  destr o y t he  rec or ds. 
 
9. 4  C o nfi de nti alit y  Discl os ure  a n d  P u bli c ati o n  P oli c y  
I nf or mati o n r elate d t o t his st u d y or ot her Ascle pi X pr o d ucts, a n y p ote ntial tra de se crets or 
c o m mer ciall y  se nsiti ve i nf or mati o n resi di n g wit hi n  t his d oc u me nt  m ust  n ot  be  discl ose d  t o a n y 
u na ut h oriz e d  i n di vi d u als, u nless  w he n  re q uire d b y  la w, or calle d u p o n  b y  a re g ulat or y b o d y. 
 
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 -p ate nta ble, are t h e s ole  
pr o pert y of Ascle pi X T h era pe utics, I nc. A n y p u bli cati o n or prese nt ati o ns relate d t o t he st u d y t hat  
are pre pare d  b y  t he Pri nci pal  I n vesti g at or or ot h er  st u d y staff m ust  be  a p pr o ve d  b y  t he S p o ns or.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  3 1  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
1 0.  BI B LI O G R A P H Y  A N D  S E L E C T E D  R E F E R E N C E S  
B ha gat N, Gri g oria n R A, T utel a A, Zar bi n M A. Dia betic mac ular e de ma: p at h o ge n esis a n d tre at m e nt.  
S ur v  O p ht hal m ol. 2 0 0 9  Ja n-Fe b; 5 4( 1): 1 -3 2.  
Ca m pa C, C osta gli ol a C, I nc or vaia C, S heri d a n C, Se merar o F, De Na dai K, et al. I nfla m mat or y  
Me diat ors a n d A n gi o ge nic Fact ors i n C h or oi dal Ne o vasc ulari zati o n: Pat h o g e neti c I nter acti o ns a n d  
T hera pe utic  I m plicati o ns. Me diat ors I nfla m m. 2 0 1 0; 2 0 1 0: 5 4 6 8 2 6.  E p u b 2 0 1 0  A u g 2 5.  
C ha n na  R,  S o p hie  R,  K h waja  A A,  D o  D V,  Hafiz  G,  N g u ye n  Q D,  et al. Fa ct ors  affecti n g  vis ual  
o utc o mes  i n patie nts  wit h  dia betic  ma c ular  e d e ma  tr eate d wit h  r a ni bi z u ma b. E y e  ( L o n d). 2 0 1 4  
Mar; 2 8( 3): 2 6 9 -7 8.  
C u n ha -Vaz J, Faria de A bre u J R, C a m p os AJ. Earl y brea k d o w n of t he bl o o d -r eti n al barrier i n 
dia bet es.  Br  J O p ht hal m ol. 1 9 7 5 N o v; 5 9( 1 1): 6 4 9-5 6.  
Da vis  S,  Al dric h  T H,  J o nes P F,  Ac hes o n  A,  C o m pt o n  D L,  Jai n V,  et al. Is ol ati o n of  a n gi o p oieti n -1,  a 
li ga n d f or t he TI E 2  re ce pt or, b y  se creti o n-tra p e x pressi o n  cl o ni n g. C ell.  1 9 9 6  Dec  2 7; 8 7( 7): 1 1 6 1 -9.  
D o D V, N g u ye n Q D, K h waja A A, C ha n na R, Se pa h YJ, S o p hie R, et al. Ra ni biz u ma b f or e de ma of  
t he ma c ula i n dia b etes st u d y: 3-ye ar o utc o mes a n d t h e nee d f or pr ol o n g e d fre q ue nt treat me nt. J A M A  
O p ht hal m ol.  2 0 1 3 Fe b; 1 3 1( 2): 1 3 9 -4 5.  
G uari g u ata L, W hiti n g D R, Ha m blet o n I, Bea gle y J, Li n ne n ka m p U, S ha w J E. Gl o bal esti mat es of  
dia bet es pre val e nce f or 2 0 1 3 a n d pr ojecti o ns f or 2 0 3 5. Dia betes Res Cli n Pract. 2 0 1 4  
Fe b; 1 0 3( 2): 1 3 7 -4 9.  
Hac kett S F, Oza ki H, Stra uss R W, W a hli n K, S uri C, Mais o n pierre P, et al. A n gi o p oi eti n 2  
e x pressi o n  i n t he reti n a: u pre g ulati o n  d uri n g  p h ysi ol o gic  a n d pat h ol o gi c  ne o vasc ularizati o n.  J Cell  
P h ysi ol.  2 0 0 0 Se p; 1 8 4( 3): 2 7 5 -8 4.  
Hac kett  S F,  Wi e ga n d  S,  Ya nc o p o ul os  G,  Ca m p oc hi ar o  P A.  A n gi o p oieti n -2  pl a ys  a n i m p orta nt r ole i n 
reti nal a n gi o ge nesis.  J Cell  P h ysi ol.  2 0 0 2  A u g; 1 9 2( 2): 1 8 2 -7.  
Heier  J S, Clar k  W L,  B o y er  D S,  Br o w n  D M,  Vitti  R,  Berli ner  AJ,  et al. I ntra vitreal afli b erce pt 
i njecti o n f or m ac ul ar e de m a d ue t o ce ntr al reti nal vei n occl usi o n: t w o-year res ults fr o m t he  
C O P E R NI C U S  st u d y. O p ht hal m ol o g y. 2 0 1 4  J ul: 1 2 1( 7): 1 4 1 4-1 4 2 0.  e 1.  
K or o bel ni k J F, H olz F G, R oi der J, O g ura Y, Si ma d er C, Sc h mi dt -Erf urt h U, et al. I ntra vitreal  
Afli berce pt I njecti o n f or Mac ular E d e ma R es ulti n g fr o m Ce ntral Reti nal Vei n Occl usi o n: O ne -Year  
Res ults  of  t he P hase  3  G A LI L E O  St u d y.  O p ht hal m ol o g y.  2 0 1 4  Ja n; 1 2 1( 1): 2 0 2-8.  
K or o bel ni k J F, D o D V, Sc h mi dt -Erf urt h U, B o yer D S, H olz F G, Heier J S, et al. I ntra vitreal  
afli ber ce pt f or dia b eti c  mac ular e d e ma.  O p ht hal m ol o g y. 2 0 1 4  N o v; 1 2 1( 1 1): 2 2 4 7 -5 4.  
Mais o n pierre P C, S uri C, J o nes P F, B art u n k o va S, Wie ga n d SJ, Ra dziej e ws ki C, et al. A n gi o p oieti n - 
2, a nat ural a nta g o nist f or Tie 2 t hat disr u pts i n vi v o a n gi o ge nesis. Sci e nce. 1 9 9 7 J ul 4; 2 7 7( 5 3 2 2): 5 5 - 
6 0.  
Mira n d o A C, S he n J, Sil va R L E, C h u Z, Sass N C, L ore nc V E, et al. A c olla ge n I V -deri ve d pe pti de  
disr u pts  al p ha 5 bet a 1  i nte gri n a n d p ot e nti ates  A n g 2/ Tie 2  si g nali n g. J CI I nsi g ht. 2 0 1 9  Fe b  2 1; 4( 4)  
 
Mira n d o,  A. C.;  Li ma  e Sil va,  R.;  C h u,  Z.;  Ca m p o c hi ar o,  P. A.;  Pa n de y,  N. B.;  P o pel,  A. S.  S u p pressi o n  
of O c ular Vasc ular I nfl a m m ati o n t hr o u g h Pe pti d e -Me diat e d Acti v ati o n of A n gi o p oieti n -Tie 2  
Si g nali n g.  I nt. J. M ol. Sci. 2 0 2 0, 2 1, 5 1 4 2.  


As cle pi X T hera pe utics, I nc.  
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
Pa ge  3 2  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
 
N g u ye n  Q D,  S ha h  S M,  Va n  A n de n  E,  S u n g  J U, Vitale S,  Ca m p oc hiar o  P A.  S u p ple me nt al  o x y ge n  
i m pr o ves di a betic  mac ular  e de m a:  a pil ot  st u d y. I n vest O p ht hal m ol  Vis  Sci.  2 0 0 4  4 5( 2): 6 1 7 -2 4.  
N g u ye n  Q D,  Tatli pi n ar  S,  S ha h  S M,  Haller  J A, Q ui nla n  E,  S u n g  J, et al. Vasc ul ar  e n d ot h eli al gr o wt h  
fact or is a critic al sti m ul us f or dia betic  mac ular  e de ma.  A m  J O p ht hal m ol.  2 0 0 6  De c; 1 4 2( 6): 9 6 1 -9.  
N g u ye n  Q D, S ha h  S M,  Heier  J S, D o  D V,  Li m  J, B o yer  D,  A bra ha m  P,  et al. Pri mar y  E n d  P oi nt  ( Si x 
M o nt hs)  Res ults  of  t he Ra ni bi z u ma b  f or E d e ma  of  t he m Ac ula  i n dia b etes  ( R E A D-2)  st u d y. 
O p ht hal m ol o g y.  2 0 0 9  N o v; 1 1 6( 1 1): 2 1 7 5 - 8 1  e 1.  
N g u ye n  Q D,  Br o w n  D M,  Marc us  D M,  B o yer  D S,  Patel  S,  Fei ner  L,  et al. Ra ni biz u ma b  f or dia betic  
mac ul ar e de ma: res ults fr o m 2 p hase III ra n d o miz e d trials: RI S E a n d RI D E. O p ht hal m ol o g y. 2 0 1 2  
A pr; 1 1 9( 4): 7 8 9 -8 0 1.  
Os hi ma Y, Deeri n g T, Os hi ma S, Na m b u H, Re d d y P S, Kale k o M. A n gi o p oieti n -2 e n h a nces reti nal  
vessel  se nsiti vit y t o vasc ular  e n d ot helial gr o wt h  f act or. J Cell P h ysi ol.  2 0 0 4  J u n; 1 9 9( 3): 4 1 2-7.  
Os hi ma  Y,  Os hi ma  S,  Na m b u  H,  Kac hi  S,  Ta ka has hi  K,  U me da  N,  et al. Differe nt  effe cts  of  
a n gi o p oieti n -2 i n differe nt vasc ular b e ds: ne w  vessels are m ost se nsiti v e. F A S E B J. 2 0 0 5  
J u n; 1 9( 8): 9 6 3-5.  
Patelli  F,  Ra di ce  P,  Giac o m otti  E.  Dia betic  ma c ular  e de ma.  De v  O p ht hal m ol.  2 0 1 4; 5 4: 1 6 4 -7 3.  
S he n  J, Fr ye  M,  Lee  B L,  Rei n ar d y  J L, Mc Cl u n g  J M, Di n g  K,  et al. Tar geti n g  V E -P T P  acti vat es  TI E 2  
a n d sta bili zes t he oc ular  vasc ulat ure.  J Cli n  I n vest, 2 0 1 4. 2 0 1 4  Oct; 1 2 4( 1 0): 4 5 6 4 -7 6.  
Sil va  R L E,  Ka na n  Y,  Mira n d o  A C,  Ki m  J, S h m ueli  R B,  L ore nc  V E,  et al. T yr osi ne  ki n ase  bl oc ki n g  
c olla g e n I V -deri ve d pe pti de s u p presses oc ul ar ne o vasc ulariz ati o n a n d vasc ular lea k a ge. Sci e nce  
tra nslati o nal me dici n e. 2 0 1 7 Ja n 1 8; 9( 3 7 3).  
T h urst o n G, R u d ge J S, I offe E, Z h o u H, R oss L, Cr oll S D, et al. A n gi o p oieti n -1 pr ote cts t he a d ult  
vasc ulat ur e  a gai nst pl as ma l ea ka g e.  Nat Me d, 2 0 0 0.  A pr; 6( 4): 4 6 0 -3.  
T h urst o n G, S uri C, S mit h K, Mc Clai n J, Sat o T N, Ya nc o p o ul os G D, et al. Lea ka g e -resista nt bl o o d 
vessels i n mic e tra ns ge nicall y o vere x pr essi n g  a n gi o p oieti n -1. Scie nc e. 1 9 9 9 Dec  
2 4; 2 8 6( 5 4 4 9): 2 5 1 1 -4.  
W o n g  A L,  Har o o n  Z A,  Wer ner  S,  De w hirst  M W,  Gr ee n ber g  C S,  Peters  K G.  Tie 2  e x pressi o n  a n d 
p h os p h or ylati o n  i n a n gi o ge nic a n d q uiesce nt  a d ult tiss ues. Circ  Res.  1 9 9 7  Oct; 8 1( 4): 5 6 7 -7 4.  
Yac ys h y n  O K,  Lai  P F,  F orse  K,  Tei c hert -K ulisze ws ka  K,  J urasz P,  St e wart  DJ.  T yr osi ne  p h os p hatase  
beta re g ulat es a n gi o p oieti n -Tie 2 si g nali n g i n  h u ma n e n d ot helial cells. A n gi o ge nesis. 2 0 0 9; 1 2( 1): 2 5 - 
3 3.  
Ya u J W, R o gers S L, Ka wasa ki R, La m o ure u x E L, K o wals ki J W, Be k T, et al. Gl o b al pre vale nc e a n d  
maj or  ris k fact ors of  dia b eti c  reti n o p at h y. Dia betes C are.  2 0 1 2  3 5( 3): 5 5 6 -6 4.  
Y ua n  H T,  K ha n ki n  E V,  Kar u ma nc hi  S A,  Pari k h  S M.  A n gi o p oieti n  2  is a p arti al  a g o nist/a nta g o nist  of  
Tie 2  si g n ali n g i n t he e n d ot heli u m.  M ol Cell  Bi ol.  2 0 0 9  A pr; 2 9( 8): 2 0 1 1 -2 2.  


Pa ge  3 3  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
As cle pi X  T hera pe utics,  I nc. 
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
A P P E N DI C E S  
A P P E N DI X  I. 
S c he d ule of  Visits  a n d  Pr oce d ures  
T a ble  I-1  S c h e d ule  of  Visits  a n d  Pr oce d u res  
 
 
Visit  
Pr oce d ures  
 
Scree ni n g  
 
Visit 1/  
B aseli ne  
 
Visit  2/  
D a y 1  
(P h o ne  C all ) 
 
Visit 3/  
Wee k  1  
 
Visit 4/  
Wee k  4  
 
Visit 5/  
Wee k  8  
 
Visit 6/  
Wee k  1 2  
Visit 7/  
Wee k 1 6  
Visit 8/  
Wee k  2 0  
 
Visit 9/  
Wee k  2 4  
Visit 1 0/ Wee k 2 8  
Visit 1 1/ Wee k 3 2  
Visit  1 2/  Wee k  3 6  
Visit 1 3/ Wee k 4 0  
Visit  1 4/  Wee k  4 4  
 
Visit 1 5/  
Wee k 4 8/  
E xit  
Visit  Wi n d o ws  ( Da ys) 
-1 4 t o -1  
0  
2  
± 2  
± 3  
± 7  
± 7  
± 7  
± 7  
± 7  
± 7  
I nf or me d C o nse nt 1 
X  
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/ E xcl usi o n 
X  
X  
 
 
 
 
 
 
 
 
 
De m o gra p hics  
X  
 
 
 
 
 
 
 
 
 
 
Me dical/ O p ht hal mic  Hist or y  
X  
 
 
 
 
 
 
 
 
 
 
C o nc o mita nt  Me dicati o ns  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Vital  si g ns 
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
P h ysical  E xa m  
X  
 
 
 
 
 
 
 
 
 
 
Uri ne  Pre g na nc y  Test 2 
X  
 
 
 
 
 
 
 
 
 
X  
Cli nical  La bs  
X  
 
 
 
 
 
 
 
X  
 
X  
A D A  Assa y 3 
X  
 
 
 
X  
 
X  
 
 
 
X  
A d verse  E ve nts 4 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
E T D R S  B C V A  
O U  
O U  
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
I O P 
O U  
O U  
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
A C  Ta p 5 
 
S E  
 
 
S E  
 
S E  
 
S E  
S E 6 
 
Slit  la m p Bi o micr osc o p y  
O U  
O U  
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
Dilate d  F u n d us  E xa m 8 
O U  
O U 9 
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
A X T 1 0 7  visi bilit y 7 
 
S E  
 
S E  
S E  
S E  
S E  
S E  
S E  
S E  
S E  
S D -O C T  
O U  
O U  
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O C T -A 5 
O U  
O U  
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
F u n d us  P h ot o gra p h y 8 
O U  
 
 
 
 
 
O U  
 
O U  
 
O U  
Fl u orescei n  A n gi o gra p h y  
O U  
 
 
 
 
 
O U  
 
O U  
 
O U  
D R S S  E val uati o n  
O U  
 
 
 
 
 
O U  
 
O U  
 
O U  
Treat me nt  assi g n me nt  
 
X  
 
 
 
 
 
 
 
 
 
St u d y  dr u g  ( A X T 1 0 7) a d mi nistrati o n 
 
S E 9 
 
 
 
 
 
 
 
 
 
H o me  O C T 5 
O U  
O U  
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
H o me  V A 5 
O U  
O U  
 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
1 T he i nf or me d  c o nse nt  f or m m ust be  si g ne d/ date d pri or t o  perf or mi n g  a n y st u d y pr oce d ur es, i ncl u di n g scr ee ni n g  pr oce d ur es.  
2 Re q uir e d  f or all f e male s u bjects of c hil d beari n g  p ote ntial.  Uri ne  pr e g na nc y tests will  be  perf or me d u nless  l ocal r e g ulati o ns/I R Bs r e q uir e a ser u m pr e g na nc y test.  
3 A d diti o nal bl o o d sa m ples will  be o btai ne d  d uri n g  cli nical  la b or at or y c ollecti o n at t he Scr ee ni n g, Wee k 4,  Wee k  1 2,  a n d Wee k 4 8  visits  f or A D A  assa y.  
4 A Es r e p orte d  after  scr ee ni n g a n d bef or e r a n d o mizati o n will  be  r e p orte d as pr e -i njecti o n A Es. 
5 Pr oce d ur e  t o be  perf or me d  at selecte d sites o nl y.  
6 At  W ee k  4 4  o nl y.  
7 A X T 1 0 7  visi bilit y  will be assesse d  via f u n d us e xa m f or all s u bjects. O pt os  will  be  use d at  selecte d sites t o e val uat e A X T 1 0 7 visi bilit y at Baseli ne  ( after I V T), Wee k 8, a n d Wee k 3 6.  
8 Ster e osc o pic  7 -fiel d or  4 -wi defiel d  c ol or  f u n d us p h ot o gr a p h y  will  be  ta ke n. 
9 I O P meas ur e me nt  m ust  be  perf or me d  pri or  t o a n d after  t he A X T 1 0 7  i njecti o n at Visit  1/ Baseli ne.  After  i njecti o n, I O P will  be  meas ur e d  3 0 ± 1 0  mi n utes.  If I O P ≥3 0 m m H g,  r e peat I O P meas ur e me nt  at 6 0 ± 1 0  mi n utes  
p ost -i njecti o n. F u n d us  e xa m  will  be  perf or me d  bef or e  a n d after  i njecti o n at t he Baseli ne  visit.  


Pa ge  3 4  of  3 4  
Versi o n  1. 0,  3 1  A u g  2 0 2 0  
 
As cle pi X  T hera pe utics,  I nc. 
C o nfi de ntial  
Pr ot oc ol  A X T 1 0 7 -C S 1 0 1  
 
A P P E N DI X  II. 
A p pr o v al  Si g n at ures  
 
 
 
 
 
F or m  
D o c.  N o. : F R M -C R -0 0 1 A. 0 0  
 
Cli ni c al  Pr ot o c ol  A p pr o v al  F or m  
 
Eff e cti v e  D at e:  4  A u g  2 0 2 0  
 
 
Pr ot o c ol  N u m b er  a n d  Titl e:  
 
A X T 1 0 7 -C S 1 0 1  
 
P h a s e  1/ 2 a  St u d y  of  t h e S af et y  a n d  Bi o a cti vit y  of  A X T 1 0 7  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  ( D M E) –  C O N G O  st u d y  
V er si o n  N u m b er  a n d  V er si o n  D at e:  V er si o n  1. 0,  3 1  A u g  2 0 2 0  
Pr ot o c ol  A m e n d m e nt( s)  (if a p pli c a bl e):  N/ A  
A p pr o v al  D at e:  3 1  A u g  2 0 2 0  
Pr ot o c ol  
A p pr o v er  
Pri nt  N a m e  
Si g n at ur e  
D at e  
d d -m m m -y y y y  
 
M e di c al  M o nit or  
 
Q u a n  D o n g  N g u y e n  
 
 
 
9/ 1/ 2 0 2 0  
 
Cli ni c al  R e s e ar c h  
 
H u a n  S h e n g  
 
 
8/ 3 1/ 2 0 2 0