Clinical trial NCT04620811
Conditions: Eosinophilic Gastritis Eosinophilic Duodenitis
Sponsor: Allakos Inc.
Start date: 2020-12-03; Completion date: 2023-07-07
Enrollment: 159 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 3, open-label, extension study to assess the long term efficacy and safety of lirentelimab given monthly.

Detailed description:

Arms: arm 1: Subjects in this arm will receive up to 18 monthly doses (3mg/kg) of lirentelimab (AK002)
Interventions: intervention 1: lirentelimab
Intervention descriptions: intervention 1: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8

Protocol documents:
Prot_SAP_000.pdf: 
An Extension Study of Lirentelimab in Eosinophilic Gastritis and/or Eosinophilic Duodenitis 
(Formerly Referred to as Eosinophilic Gastroenteritis) 
NCT Number: NCT04620811 
Document Date: 23 March 2022 
IRB Approval Date: 08 Apr 2022 


8 2 5 I n d u stri al R o a d, S uit e 5 0 0, S a n C arl os, C A 9 4 0 7 0
Pa ge 1 of 9 9
Cli ni c al Res e a rc h P r ot o c ol A K 0 0 2- 0 1 6 X
A P h as e 3, M ultice nter, O pe n- L a bel, E xte nsi o n St u d y t o E v al u ate t he
Effic ac y a n d S afet y of A K 0 0 2 i n P atie nts t h at were Pre vi o usl y E nr olle d i n 
A K 0 0 2- 0 1 6 or A K 0 0 2- 0 1 2 St u dies a n d h a ve E osi n o p hilic G astritis a n d/ or 
E osi n o p hilic D u o de nitis (f or m erl y referre d t o as E osi n o p hilic G astr oe nteritis)
P r ot oc ol N u m ber
A K 0 0 2- 0 1 6 X 
Versi o n a n d D ate
Ori gi nal  
0 2 A u g ust 2 0 2 0
A me n d me nt 1
1 5 J ul y 2 0 2 1
A me n d me nt 2 
2 3 M arc h 2 0 2 2 
I n v esti g ati o n al P r o d u ct
A K 0 0 2
St u d y P h ase
3 
S p o ns or
Alla k os I nc.
8 2 5 I n d ustri al R oa d, S uite 5 0 0, Sa n Carl os, C A 9 4 0 7 0
Me dic al M o nit or
Na me:
, M D
T ele p h o ne: 
 
E mail: 
A p pr o v al:
, M D, M B A, 
Date
C o nfi de nti alit y St ate me nt
T his c o nfi de nti al i nf or mati o n a b o ut a n i n vesti gati o nal pr o d uct is pr o vi de d f or t he e xcl usi v e use 
of I n vesti gat ors of t his pr o d uct a n d is s u bject t o recall at a n y ti me. T he i nf or mati o n i n t his 
d oc u me nt ma y n ot be discl ose d u nless fe deral or state la w or re g ulati o ns re q uire s uc h discl os ure. 
S u bject t o t he f ore g oi n g, t his i nf or mati o n ma y be discl ose d o nl y t o t h ose pers o ns i n v ol v e d i n t he 
st u d y w h o ha ve a nee d t o k n o w, wit h t he o bli gati o n n ot t o f urt h er disse mi n ate t his i nf or mati o n.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 of 9 9 
 
I n v esti g at o r P r ot o c ol A g ree m e nt
I ha ve rea d t he pr ot oc ol s pecifie d b el o w. I n m y f or mal ca pacit y as Pri nci pal I n vesti gat or, m y 
d uties i ncl u de e ns uri n g t h e safet y of t he st u d y patie nts e nr olle d u n der m y s u per visi o n a n d 
pr o vi di n g All a k os, I n c. wit h c o m plete a n d ti mel y i nf or mati o n, as o utli n e d i n t he pr ot oc ol. It is 
u n derst o o d t hat all i nf or mati o n pertai ni n g t o t h e st u d y will be hel d strictl y c o nfi de ntial a n d t hat 
t his c o nfi d e nti alit y re q uir e me nt a p plies t o all st u d y staff at t his site. F urt h er m ore, o n be half of 
t he st u d y staff a n d m yself, I a gree t o mai ntai n t he pr oce d ures re q uire d t o carr y o ut t he st u d y i n 
acc or da nce wit h acce pte d G o o d Cli nical Pr acti ce ( G C P) pri n ci ples a n d t o a bi de b y t he ter ms of 
t his pr ot oc ol.
P r ot oc ol N u m ber:
A K 0 0 2- 0 1 6 X 
P r ot oc ol Title:   
A P h ase 3, M ultice nter, O pe n- La bel, E xte nsi o n St u d y t o E val u ate t he 
Efficac y a n d Safet y of A K 0 0 2 i n Patie nts t h at were Pr e vi o usl y E nr olle d i n 
A K 0 0 2- 0 1 6 or A K 0 0 2- 0 1 2 St u dies a n d h a ve E osi n o p hilic Gastritis a n d/ or 
E osi n o p hilic D u o de nitis (f or merl y referre d t o as E osi n o p hili c 
Gastr oe nteritis)  
Ori gi n al P r ot oc ol:  
0 2 A u g ust 2 0 2 0 
A me n d me nt 1:   
1 5 J ul y 2 0 2 1 
A me n d me nt 2:  
2 3 M arc h 2 0 2 2  
I n v esti g at or’s N a me ( pri nte d):  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Si g n at ure:
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
D ate:
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 of 9 9 
 
T a bl e of C o nt e nts
Cli ni c al Rese arc h P r ot oc ol A K 0 0 2- 0 1 6 X ................................................................................. 1
I n v esti g at or P r ot oc ol A gree me nt .............................................................................................. 2
T a bl e of C o nte nts ...................................................................................................................... 3
List of T a bles...................................................................................................................... 8
List of A b bre viati o ns .......................................................................................................... 9
1.
P r ot oc ol S y n o psis............................................................................................................ 1 1
2.
B a c k gr o u n d ..................................................................................................................... 2 0
2. 1 
Si glec- 8 a n d A K 0 0 2 .............................................................................................. 2 0
2. 2  
O ver vie w of N o ncli nical St u dies........................................................................... 2 0
2. 3  
O ver vie w of Cli nical St u dies................................................................................. 2 1
2. 4 
E osi n o p hilic Gastr oi ntesti nal Dis or ders ................................................................. 2 3
3.
R ati o n ale f or St u d y a n d D ose Selecti o n ......................................................................... 2 4
4.
St u d y O bjecti ves.............................................................................................................. 2 5
5.
St u d y Desi g n.................................................................................................................... 2 5
5. 1 
St u d y O ver vie w..................................................................................................... 2 5
5. 2 
S c he d ule of E ve nts ................................................................................................ 2 7
6.
Criteri a f or E v al u ati o n ................................................................................................... 3 2
6. 1 
S afet y E n d p oi nts ................................................................................................... 3 2
6. 2 
P har mac o ki netic E n d p oi nts ................................................................................... 3 2
6. 3 
Efficac y E n d p oi nts ................................................................................................ 3 2
6. 4 
P har mac o d y na mic E n d p oi nts................................................................................. 3 3
7.
P atie nt Selecti o n.............................................................................................................. 3 3
7. 1  
N u m ber of Patie nts ................................................................................................ 3 3
7. 2 
St u d y P o p ulati o n ................................................................................................... 3 3


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 of 9 9 
 
7. 3 
I ncl usi o n Criteria................................................................................................... 3 3
7. 4 
E xcl usi o n Criteria.................................................................................................. 3 4
8.
C o nc urre nt Me dic ati o ns................................................................................................. 3 4
8. 1 
Pr o hi bite d Me dicati o ns.......................................................................................... 3 5
8. 2  
All o we d Me dicati o ns............................................................................................. 3 5
9.
St u d y Tre at me nt............................................................................................................. 3 6
9. 1 
F or m ulati o n of T est Pr o d uct .................................................................................. 3 6
9. 2 
St u d y Dr u g Pac ka gi n g a n d La beli n g ...................................................................... 3 6
9. 3 
S u p pl y of St u d y Dr u g t o t he I n vesti gati o nal Sit e .................................................... 3 6
9. 4 
St u d y Dr u g D osa ge a n d D ose Re gi me n ................................................................. 3 6
9. 5 
Pre parati o n of St u d y Dr u g..................................................................................... 3 7
9. 6 
St u d y Dr u g A d mi nistr ati o n .................................................................................... 3 7
9. 7 
St u d y Dr u g St ora ge ............................................................................................... 3 8
9. 8 
T e m perat ure E xc ursi o ns........................................................................................ 3 8
9. 9 
St u d y Dr u g Acc o u nta bilit y .................................................................................... 3 8
1 0.
P atie nt N u m beri n g, Str atific ati o n, R a n d o miz ati o n, a n d Bli n di n g ................................ 3 9
1 0. 1
Patie nt N u m beri n g................................................................................................. 3 9
1 0. 2
Stratificati o n a n d Ra n d o mizati o n........................................................................... 3 9
1 0. 3
Bli n di n g ................................................................................................................ 3 9
1 1.
St u d y P r oce d ures a n d G ui deli nes................................................................................... 3 9
1 1. 1
Dietar y a n d Lifest yle Restricti o ns.......................................................................... 3 9
1 1. 2
P h ar mac o d y na mic/ Efficac y- Relate d Pr o ce d ures.................................................... 4 0
1 1. 2. 1  
E G/ E o D P R O Q uesti o n naire .................................................................... 4 0
1 1. 2. 2  
S h ort F or m- 3 6 H ealt h a n d Well- Bei n g S ur ve y......................................... 4 0
1 1. 2. 3  
C o m plete Bl o o d C o u nt wit h Differe ntial .................................................. 4 0


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 of 9 9 
 
1 1. 2. 4  
Es o p ha g o- Gastr o- D u o de n os c o p y wit h Bi o ps y ......................................... 4 1
1 1. 2. 5  
Baseli ne Diet Assess me nt ........................................................................ 4 1
1 1. 3
Safet y- Relate d Pr oce d ures..................................................................................... 4 1
1 1. 3. 1  
C o nc o mita nt Me dicati o ns ........................................................................ 4 1
1 1. 3. 2
B o d y Wei g ht ........................................................................................... 4 2
1 1. 3. 3
S y m pt o m- Directe d P h ysical E xa mi nati o n................................................ 4 2
1 1. 3. 4
Vital Si g ns............................................................................................... 4 2
1 1. 4
Cli nical La b orat or y Meas ure me nts........................................................................ 4 2
1 1. 4. 1  
C o m plete Bl o o d C o u nt wit h Differe ntial .................................................. 4 3
1 1. 4. 2  
Bl o o d C he mistr y Pr ofil e .......................................................................... 4 4
1 1. 4. 3  
Pre g na nc y T est ........................................................................................ 4 4
1 1. 4. 4  
Effecti ve Met h o ds of C o ntrace pti o n f or Alla k os St u dies .......................... 4 4
1 1. 4. 5  
Uri nal ysis ................................................................................................ 4 5
1 1. 4. 6  
A nti- A K 0 0 2 A nti b o dies ........................................................................... 4 6
1 1. 4. 7  
P har mac o ki netics a n d St ora ge ................................................................. 4 6
1 1. 4. 8  
Hista mi ne a n d Tr y ptase ........................................................................... 4 6
1 1. 4. 9  
I g E .......................................................................................................... 4 6
1 1. 4. 1 0  C O VI D- 1 9 T esti n g.................................................................................. 4 7
1 2.
E v al u ati o ns a n d P r oce d ures b y Visit.............................................................................. 4 7
1 2. 1
Pri or t o E xte nsi o n Da y 1........................................................................................ 4 7
1 2. 2
E xte nsi o n Da y 1 – First Da y of D osi n g.................................................................. 4 7
1 2. 3
E xte nsi o n Da y 2 9 ( ± 3) – D ose 2 ............................................................................ 4 9
1 2. 4
E xte nsi o n Da y 5 7 ( ± 3) – D ose 3 ............................................................................ 5 0
1 2. 5
E xte nsi o n Da y 8 5 ( ± 3) – D ose 4 ............................................................................ 5 1
1 2. 6
E xte nsi o n Da y 1 1 3 ( ± 3) – D ose 5 .......................................................................... 5 2
1 2. 7
E xte nsi o n Da y 1 4 1 ( ± 3) – D ose 6 .......................................................................... 5 3


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 of 9 9 
 
1 2. 8
E xte nsi o n Da y 1 6 9 ( ± 3) – D ose 7 .......................................................................... 5 4
1 2. 9
E xte nsi o n Da y 1 9 7 ( ± 3) – D ose 8 .......................................................................... 5 5
1 2. 1 0
E xte nsi o n Da y 2 1 1 ( ± 3) – First E G D..................................................................... 5 7
1 2. 1 1
E xte nsi o n Da y 2 2 5 t o Da y 4 7 7 ( ± 3) – D oses 9 t o 1 8.............................................. 5 7
1 2. 1 2
E xte nsi o n Da y 5 0 5 ( ± 3) or 2 8 ( ± 3) Da ys after Last D ose – F oll o w- u p E G D.......... 5 8
1 2. 1 3
E xte nsi o n Da y 5 1 2 ( ± 3) or 3 5 ( ± 3) Da ys after Last D ose – F oll o w- u p Visit 1 ........ 5 9
1 2. 1 4
E xte nsi o n Da y 5 3 3 ( ± 3) or 5 6 ( ± 3) Da ys after Last D ose – F oll o w- u p Visit 2........ 5 9
1 2. 1 5
E xte nsi o n Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) Da ys after Last D ose – F oll o w- u p Visit 3........ 6 0
1 3.
A d verse E v e nt Re p orti n g a n d D oc u me nt ati o n .............................................................. 6 0
1 3. 1
A d verse E ve nts...................................................................................................... 6 0
1 3. 2
Seri o us A d verse E ve nts......................................................................................... 6 1
1 3. 3
A d verse E ve nts of S pecial I nterest ......................................................................... 6 2
1 3. 4
I nf usi o n- Relate d Reacti o ns .................................................................................... 6 2
1 3. 5
A na p h yla xis .......................................................................................................... 6 3
1 3. 6
E v al uati n g A d verse E ve nts a n d Seri o us A d verse E ve nts........................................ 6 3
1 3. 6. 1  
Esta blis hi n g Dia g n osis ............................................................................. 6 3
1 3. 6. 2  
Assess me nt of I nte nsit y ........................................................................... 6 3
1 3. 6. 3  
Assess me nt of Ca usalit y t o St u d y Dr u g ................................................... 6 4
1 3. 6. 4  
Assess me nt of Ca usalit y t o St u d y Pr oce d ure ............................................ 6 5
1 3. 6. 5  
Acti o n T a ke n ........................................................................................... 6 5
1 3. 6. 6  
Assess me nt of O utc o m e........................................................................... 6 5
1 3. 7
A d verse E ve nt Re p orti n g Pr oce d ures ..................................................................... 6 6
1 3. 7. 1  
All A d verse E ve nts .................................................................................. 6 6
1 3. 7. 2  
Seri o us A d verse E ve nt Re p orti n g............................................................ 6 6
1 3. 7. 3  
Pre g na nc y Re p orti n g ............................................................................... 6 7
1 3. 7. 4  
A d verse E ve nt of S pecial I nterest Re p orti n g ............................................ 6 8


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 of 9 9 
 
1 3. 8
Me dical M o nit ori n g ............................................................................................... 6 8
1 3. 9
St u d y Wit h dra wal Criteria ..................................................................................... 6 9
1 3. 1 0
St u d y St o p pi n g R ules ............................................................................................ 6 9
1 4.
Disc o nti n u ati o n a n d R e pl a ce me nt of P atie nts ............................................................... 6 9
1 4. 1
D efi niti o n of St u d y C o m pleti o n............................................................................. 6 9
1 4. 2
E arl y Disc o nti n uati o n of St u d y Dr u g..................................................................... 7 0
1 5.
St atistic al Met h o ds a n d Ge ner al C o nsi der ati o ns ........................................................... 7 0
1 5. 1
Sa m ple Size........................................................................................................... 7 1
1 5. 2
D ata Sets A nal yze d................................................................................................ 7 1
1 5. 3
D e m o gra p hic a n d Baseli ne C haracteristics ............................................................ 7 1
1 5. 4
Patie nt Dis p ositi o n ................................................................................................ 7 1
1 5. 5
A nal ysis of Safet y E n d p oi nts ................................................................................. 7 1
1 5. 6
P h ar mac o d y na mic/ Efficac y- Relate d A nal yses....................................................... 7 2
1 5. 7
Patie nt C o nfi d e nti alit y........................................................................................... 7 2
1 6.
D at a C ollecti o n, Rete nti o n, a n d M o nit ori n g .................................................................. 7 3
1 6. 1
D ata C ollecti o n I nstr u me nts .................................................................................. 7 3
1 6. 2
D ata Ma na ge me nt Pr oce d ures................................................................................ 7 3
1 6. 3
D ata Q ualit y C o ntr ol a n d Re p orti n g....................................................................... 7 3
1 6. 4
D ata base L oc k....................................................................................................... 7 4
1 6. 5
Arc hi vi n g of Data .................................................................................................. 7 4
1 6. 6
A vaila bilit y a n d Rete nti o n of I n vesti gati o nal Rec or ds............................................ 7 4
1 6. 7
M o nit ori n g ............................................................................................................ 7 5
1 7.
A d mi nistr ati ve, Et hic al, a n d Re g ul at or y C o nsi der ati o ns .............................................. 7 5
1 7. 1
Pr ot oc ol A me n d me nts ........................................................................................... 7 5
1 7. 2
I nstit uti o nal Re vie w B oar d .................................................................................... 7 5


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 8 of 9 9 
 
1 7. 3
I nf or me d C o nse nt F or m......................................................................................... 7 6
1 7. 4
P u blicati o ns ........................................................................................................... 7 6
1 7. 5
Cli nical Trial Re gistrati o n ..................................................................................... 7 7
1 7. 6
Pa y me nt t o Patie nts............................................................................................... 7 7
1 7. 7
I n vesti g at or Res p o nsi bilities.................................................................................. 7 7
1 8.
Refere nces ....................................................................................................................... 7 9
1 9.
A p pe n di ces ...................................................................................................................... 8 1
1 9. 1
A p pe n di x 1: E G/ E o D P R O Q uesti o n naire.............................................................. 8 2
1 9. 2
A p pe n di x 2: S F- 3 6 Healt h a n d Well- Bei n g S ur ve y Q uesti o n naire ......................... 8 5
1 9. 3
A p pe n di x 3: C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts, Versi o n 5. 0....... 9 1
1 9. 4
A p pe n di x 4: e P R O T eac hi n g T o ol ......................................................................... 9 2
1 9. 5
A p pe n di x 5: A d diti o nal Q uesti o ns......................................................................... 9 6
1 9. 6
A p pe n di x 6: E G D Hist ol o g y Directi o ns................................................................. 9 7
1 9. 7
A p pe n di x 7: Sa m ps o n’s Criteria of A na p h yla xis .................................................... 9 9
List of T a bles 
T a ble 1  
Sc he d ule of Assess me nts.................................................................................... 2 8
T a ble 2  
A d verse E ve nt Se verit y f or A d verse E ve nts....................................................... 6 4
T a ble 3  
A d verse E ve nt Relati o ns hi p t o St u d y Dr u g ........................................................ 6 4
T a ble 4  
A d verse E ve nt Relati o ns hi p t o St u d y Pr oce d ure ................................................. 6 5


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 of 9 9 
 
List of A b bre vi ati o ns 
A C 
All er gic c o nj u ncti vitis 
A D A 
A nti- dr u g a nti b o d y 
A D C C 
A nti b o d y- de pe n de nt c ell ul ar c yt ot o xicit y 
A E 
A d v erse e ve nt(s) 
A E SI 
A d verse e ve nt(s) of s pe cial i nterest
A L T 
Ala ni ne a mi n otra nsferase 
A S T 
As part ate a mi n otra nsferase 
A T C 
A nat o mic al T hera pe utic C he mical Classifi cati o n S yste m 
C 
Ce nti gra de 
C B C 
C o m pl et e bl o o d c o u nt 
C F R 
C o de of Fe deral Re g ul ati o n 
c m 
Ce nti meter 
C O VI D- 1 9 
C or o na vir us dise ase of 2 0 1 9 
C S 
Cli ni call y si g nifi ca nt
C T C A E 
C o m m o n Ter mi n ol o g y Crit eri a f or A d verse E ve nts  
D S Q 
D ys p ha gia S y m pt o m Q uesti o n naire 
e C R F 
El ectr o nic Case Re p ort F or m 
E D C 
El ectr o nic Data Ca pt ure (s yste m) 
E G 
E osi n o p hilic gastritis 
E G D 
Es o p ha g o- Gastr o- D u o de n osc o p y 
E G E 
E osi n o p hilic gastr oe nteritis 
E GI D
E osi n o p hilic gastr oi ntesti nal dis or ders
E o D 
E osi n o p hili c d u o de nitis
E o E 
E osi n o p hili c Es o p ha gitis 
E T 
E arl y t er mi n ati o n 
E xt 
E xte nsi o n 
F D A 
F o o d a n d Dr u g A d mi nistrati o n 
G C P
G o o d Cli ni cal Practi ce
H E S 
H y p ere osi n o p hili c S y n dr o me 
HI P A A 
Healt h I ns ura nce P ort a bilit y a n d Acc o u nta bilit y Act 
h pf
Hi g h- p o wer fi el d
I C E
I nterc urre nt e v e nts


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 1 0 of 9 9 
 
I C F 
I nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I g E 
I m m u n o gl o b uli n E 
I g G 1 
I m m u n o gl o b uli n G 1
I P 
I n vesti gati o nal pr o d uct 
I R B 
I nstit uti o nal Re vi e w B o ar d 
I R R 
I nf usi o n relat e d re acti o n 
I R T
I nteracti ve res p o nse t ec h n ol o g y (s yste m)
I S M
I n d ole nt s yst e mic mast oc yt osis 
I V 
I ntra ve n o us 
k g 
Kil o gra m 
L A R C 
L o n g- Acti n g Re versi bl e C o ntrace pti ves 
Me d D R A 
Me dical Dicti o nar y f or Re g ulat or y Acti viti es 
m g 
Milli gra m 
M T D 
Ma xi m u m t olerat e d d ose 
Na Cl 
S o di u m c hl ori de 
N C S
N ot cli nicall y si g nifica nt 
N K 
Nat ural killer 
P GI C 
Patie nt Gl o bal I m pressi o n of C ha n ge 
PI D 
Patie nt i de ntifi cati o n n u m ber 
P K 
P har ma c o ki netic(s) 
S A E 
Seri o us a d verse e ve nt(s)
S F- 3 6 
S h ort- F or m Healt h a n d W ell Bei n g S ur ve y 
Si glec 
Siali c aci d- bi n di n g, i m m u n o gl o b uli n-li k e lecti n 
T E A E 
Treat m e nt-e mer ge nt a d verse e ve nt(s) 
T S S 
T otal S y m pt o m Sc ore
U L N 
U p per li mit of n or mal 
U S P 
U nit e d States P har m ac o pei a 
w/ v 
W ei g ht/ v ol u me 
W FI 
W ater f or I nj ecti o n 
W H O D D 
W orl d He alt h Or ga nizati o n Dr u g Dicti o nar y 
W O C B P 
W o me n of c hil d be ari n g p ot e ntial 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 1 1 of 9 9 
 
1.
P r ot oc ol S y n o psis
St u d y Title
A P h ase 3, M ultice nter, O pe n- La bel, E xte nsi o n St u d y t o E val uat e t he
Efficac y a n d S afet y of A K 0 0 2 i n P atie nts T hat Were Pre vi o usl y E nr oll e d i n 
A K 0 0 2- 0 1 6 or A K 0 0 2- 0 1 2 St u dies a n d h a ve E osi n o p hilic Gastritis a n d/ or 
E osi n o p hili c D u o de nitis (f or m erl y referre d t o as E osi n o p hili c Gastr o e nteritis) 
S p o ns or 
Alla k os I nc., 8 2 5 I n d ustrial R oa d, S uit e 5 0 0, Sa n Carl os, C A 9 4 0 7 0 U S A 
N u m ber of Sites
A p pr o xi matel y 6 0 cli ni cal ce nters i n t h e U nit e d St ates a n d A ustrali a
N o ncli nic al 
B ac k gr o u n d 
A K 0 0 2 is a h u m a ni ze d n o n-f uc os yl ate d i m m u n o gl o b uli n G 1 (I g G 1) m o n ocl o nal 
a nti b o d y directe d a gai nst Si glec- 8, a me m ber of t he C D 3 3-relate d fa mil y of si alic 
aci d- bi n di n g, i m m u n o gl o b uli n-li ke lecti ns ( Si glecs). Si glec- 8 has a restri ct e d 
tiss ue distri b uti o n, e x press e d selecti v el y o n t he s urface of mat ure e osi n o p hils a n d 
mast cells, b ut n ot i n earl y prec urs ors of t hese cell p o p ulati o ns. I n bl o o d, bi n di n g 
of A K 0 0 2 t o Si glec- 8 i n d uces a nti b o d y- de pe n de nt cell ul ar c yt ot o xicit y ( A D C C) 
a gai nst e osi n o p hils, lea di n g t o ra pi d a n d s ustai ne d de pleti o n of t hese cells fr o m 
t h e circ ulati o n. I n t he tiss ue, A K 0 0 2 i n d uces direct a p o pt osis of e osi n o p hils a n d 
i n hi biti o n of mast cells. 
Cli nic al 
B ac k gr o u n d 
A K 0 0 2, a d mi nist ere d as a n i ntra ve n o us i nf usi o n, has bee n pre vi o usl y test e d i n 
healt h y v ol u nt eers a n d i n patie nts wit h i n d ole nt s yste mic m ast oc yt osis (I S M), 
c hr o nic urticaria ( C U), se vere all er gic c o nj u ncti vitis ( A C), m ast cell gastritis, a n d 
e osi n o p hilic gastritis ( E G) a n d/ or e osi n o p hilic d u o de nitis ( E o D), w hic h was 
referre d t o as e osi n o p hili c gastr oe nt eritis ( E G E) i n pre vi o us st u dies. M ulti ple 
d oses of 3 m g/ k g ha ve bee n gi ve n t o patie nts wit h I S M, C U, se vere A C, E G, 
a n d/ or E o D. I n t hese st u dies, patie nts re p ort e d i m pr o v e m e nts i n disease 
s y m pt o ms wit h A K 0 0 2 p har mac o d y na mic ( P D) acti vit y bei n g o bser ve d f or 
pr ol o n ge d p eri o ds of ti m e a n d p har mac o ki n etic ( P K) para meters de m o nstrati n g a 
half-life a me na bl e t o a d mi nistrati o n e ver y 4 wee ks. 
T o dat e, healt h y v ol u nteers a n d patie nts wit h I S M, C U, se v ere A C, E G/ E o D, 
E o E, a n d m ast cell gastritis ha ve bee n e nr olle d i n cli ni cal st u dies. I n g e neral, 
A K 0 0 2 has b ee n well t olerate d. T he m ost c o m m o n treat me nt-e mer ge nt a d verse 
e ve nts ( T E A E) o bser ve d were i nf usi o n-relate d reacti o n (I R R). M ost I R R were 
mil d t o m o derat e a n d res ol ve d o n t heir o w n, wit h n o treat me nt re q uire d; I R R t hat 
were seri o us, res ol ve d wit hi n a p pr o xi matel y 2 4 h o urs. 
I n all st u dies t here was a tra nsie nt decrease i n l y m p h oc yt e c o u nt after t he A K 0 0 2 
i nf usi o n ( us uall y res ol vi n g wit hi n 1 da y) t h at was n ot ass ociat e d wit h a n y cli nical 
c o nse q ue nce a n d a s ustai ne d s u p pressi o n of e osi n o p hils t hat was c o nsiste nt wit h 
t h e m ec ha nis m of acti o n of A K 0 0 2. N o si g nifi ca nt tre n ds were o bs er ve d f or 
c ha n ges i n vital si g ns, el ectr ocar di o gra ms ( E C G), cli nical la b orat or y para met ers, 
or p h ysical e xa mi nati o n. 




Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 1 3 of 9 9 
 
T ar get Dise as e 
B ac k gr o u n d a n d 
R ati o n ale c o nt. 
T he dia g n osis is base d o n cli nical prese nt ati o n ( gastr oi ntesti nal s y m pt o ms) 
c o m bi ne d wit h i ncrease d tiss ue e osi n o p hils i n bi o ps y s peci me ns fr o m t he 
st o mac h a n d/ or d u o de n u m wit h o ut a n y ot her ca use f or t he e osi n o p hilia. 
I n v ol ve m e nt of t he s mall i ntesti ne is t y picall y ass ess e d b y perf or mi n g d u o de nal 
bi o psies usi n g a n es o p ha g o- gastr o- d u o de n os c o p y ( E G D) a n d has bee n referre d t o 
as e osi n o p hilic gastr oe nteritis or e osi n o p hilic e nteritis t h o u g h e osi n o p hilic 
d u o de nitis is m ore a p pr o priate. 
T he g astr oi ntesti nal s y m pt o ms are belie ve d t o be d ue t o t he rel ease of 
i nfl a m mat or y m e di at ors fr o m acti vate d e osi n o p hils, a n d li kel y mast cells. 
S y m pt o ms t h at are ofte n s e vere a n d d e bilitati n g c o m m o nl y i ncl u de a b d o mi nal 
pai n, na us ea, bl oati n g, earl y sati et y, f ull ness bef ore fi nis hi n g a m eal, a b d o mi nal 
cra m pi n g, v o miti n g, di arr hea, a n d wei g ht l oss ( Al h m o u d, 2 0 1 6 ; L o pez- Me di na, 
2 0 1 5 ; Ma ns o or, 2 0 1 7 ; R ee d, 2 0 1 5 ). J e nse n (2 0 1 6 ) esti mate d t he pre vale nce of E G 
a n d E o D t o be 6. 3/ 1 0 0, 0 0 0 a n d 8. 4/ 1 0 0, 0 0 0, res pecti vel y (f or pati e nts fr o m 1 t o 
6 4 years of a ge). M a ns o or ( 2 0 1 7) esti m ate d t he o verall pre val e nce of E G t o be 
5. 1/ 1 0 0, 0 0 0 pers o ns.  
P atie nts ma y als o ha v e c o n c o mita nt at o pic diseases li k e f o o d all er g y, ast h m a a n d 
at o pic der matitis, w hi c h f urt her i m pacts q ualit y of life a n d c o ntri b utes t o healt h 
care c osts. A d diti o nall y, 8 % t o 1 0 % of pati e nts ha v e c o nc o mit a nt E o E 
(Je nse n, 2 0 1 6).  
T here are n o F D A- a p pr o v e d treat m e nts f or E G a n d/ or E o D. C urre nt t h era pies a n d 
dis ease m a na ge me nt i ncl u des dietar y restri cti o n/eli mi nati o n, pr ot o n p u m p 
i n hi bit ors ( P PI), a nti hist a mi nes, s yste mic or s wall o we d c orti c ost er oi ds, a n d 
occasi o nal off-l a bel use of i m m u n o m o d ulat or y bi ol o gics ( Pr ussi n, 2 0 1 4 ; 
R ee d, 2 0 1 5; Z ha n g, 2 0 1 7 ).  
Pr ot o n p u m p i n hi bit ors ha ve little t o n o be nefit i n patie nts wit h E G a n d/ or E o D, 
des pite re p orts of pr o vi di n g parti al be nefit i n s o me patie nts wit h E o E ( Katz, 
2 0 1 3 ). R estrict e d/ el e me ntal diets are n ot effecti ve l o n g-ter m treat m e nt as t he y 
re q uire strict c o m pli a nce a n d, i n t he case of el e m e ntal diets, are e x pe nsi ve a n d are 
ofte n n ot rei m b urse d b y i ns ura nce. I n a d diti o n, c o m pli a nce is ver y p o or a n d 
pati e nt q ualit y of life is greatl y i m pacte d ( B e dell, 2 0 1 8 ; P et ers o n, 2 0 1 3 ; 
Wec hsler, 2 0 1 4 ). C orti c oster oi ds, s yste mic or s wall o we d, ha ve b ee n s h o w n t o 
pr o vi de s y m pt o m reli ef b ut are n ot a p pr o priate f or l o n g-ter m treat m e nt d ue t o 
n u mer o us si de effects a n d ass o ciate d ris ks i ncl u di n g a dre nal i ns ufficie nc y, b o ne 
de mi neralizati o n, i ncrease d c ha nce of i nfecti o n, oste o p or osis, be ha vi oral iss u es, 
a n d wei g ht gai n. 
B y mar ke dl y re d uci n g t he n u m ber of bl o o d a n d tiss ue e osi n o p hils a n d i n hi biti n g 
t h e acti vati o n of m ast cells, A K 0 0 2 m a y be us ef ul i n t he treat m e nt of pati e nts 
wit h E G a n d/ or E o D. T his pre mise is s u p p ort e d b y t h e P hase 2 dat a wit h A K 0 0 2 
t h at s h o ws si g nifi ca nt i m pr o ve m e nts i n hist ol o g y a n d s y m pt o ms i n t hese pati e nts. 
Gi ve n t here are n o a p pr o ve d t hera pi es f or t hese c hr o nic a n d d e bilit ati n g dis eases, 
bett er treat m e nt o pti o ns are clearl y nee de d t o m a na ge E G a n d E o D. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 1 4 of 9 9 
 
R ati o n ale f or D ose 
S el ecti o n 
B ase d o n e x perie nce wit h A K 0 0 2 i n healt h y v ol u nteers a n d i n patie nts wit h I S M, 
C U, s e vere A C, a n d E G/ E o D, t he pr o p ose d A K 0 0 2 d ose re gi m e n is 1 8 t ot al d oses 
of 3 m g/ k g A K 0 0 2 a d mi nistere d e ver y 4 wee ks. 
T o dat e, a ra n ge of A K 0 0 2 d oses fr o m 0. 0 0 0 3 m g/ k g t o 1 0 m g/ k g ha ve bee n 
teste d a n d t he m a xi m u m t olerat e d d ose ( M T D) has n ot b ee n reac he d. I n t he 
d o u ble- bli n d, place b o-c o ntr olle d P hase 2 st u d y i n patie nts wit h E G a n d/ or E o D, 
2 d ose le vels were e val uat e d: a l o wer d ose re gi me n ( 4 m o nt hl y d oses of A K 0 0 2 
at 0. 3, 1, 1, a n d 1 m g/ k g) a n d a hi g her d ose re gi m e n ( 4 m o nt hl y d oses of A K 0 0 2 
at 0. 3, 1, 3, a n d 3 m g/ k g).  
B ot h re gi m e ns pr o d uce d dra matic re d u cti o n i n tiss ue e osi n o p hils a n d were 
ass ociate d wit h s u bsta ntial i m pr o ve me nt i n s y m pt o ms. H o we ver, n u mericall y 
great er i m pr o ve me nts were o bser ve d i n t he hi g h d ose ar m c o m pare d wit h t he l o w 
d ose ar m.  
As t here were n o differe nces i n safet y a n d t olera bilit y bet wee n t he 2 d osi n g 
re gi m e ns a n d t he hi g her d ose re gi m e n a p peare d t o be m ore effecti ve, t he 3 m g/ k g 
d ose was selecte d as t he starti n g d ose i n t his P h as e 3 o pe n-la bel e xt e nsi o n st u d y. 
N u m ber of P atie nts 
U p t o a p pr o xi m at el y 1 8 3 patie nts c o ul d be e nr oll e d, base d o n e nr oll m e nt of 
St u d y A K 0 0 2- 0 1 6. 
St u d y Desi g n 
T his is a P has e 3, m ultice nter, o pe n-la bel, e xt e nsi o n st u d y t o e val uat e t he s afet y 
a n d efficac y of A K 0 0 2 i n pati e nts t hat were pre vi o usl y e nr olle d i n A K 0 0 2- 0 1 6 or 
A K 0 0 2- 0 1 2 st u dies a n d ha ve E G a n d/ or E o D. I n a d diti o n, t his st u d y pr o vi des t he 
o pti o n of acti ve treat m e nt i n pati e nts w h o recei v e d pl ace b o i n t he d o u ble- bli n d, 
place b o-c o ntr oll e d, ra n d o mize d A K 0 0 2- 0 1 6 st u d y.  
P atie nts e nr olle d i n t he st u d y will recei ve u p t o 1 8 i nf usi o ns of A K 0 0 2 
a d mi nistere d e ver y 4 wee ks a n d will be f oll o we d f or 1 2 wee ks after last d ose. 
D uri n g t he E xte nsi o n St u d y A K 0 0 2- 0 1 6 X, pati e nts will m ai ntai n t he sa m e patie nt 
n u m b er t hat was assi g ne d i n St u d y A K 0 0 2- 0 1 6 a n d St u d y A K 0 0 2- 0 1 2, as 
a p plica ble. 
S afet y will be assesse d b y b o d y wei g ht, vital si g ns, s y m pt o m- direct e d p h ysi cal 
e xa mi nati o n, c o m plete bl o o d c o u nt ( C B C) wit h differe nti al, bl o o d c he mistr y, 
uri nal ysis, a n d assess me nt of a d verse e ve nts (i ncl u di n g a d verse e ve nts of s pecial 
i nterest a n d seri o us a d v erse e ve nts). I n a d diti o n, bl o o d sa m ples will b e o btai ne d 
f or e v al u ati o n of P K a n d a nti- dr u g a nti b o di es ( A D A).  
T he st u d y is desi g ne d as f oll o ws: 
P atie nts c o m pleti n g St u d y A K 0 0 2- 0 1 6 d osi n g a n d e nteri n g t he e xte nsi o n
st u d y m a y be gi n e xte n de d d osi n g 1 da y after t he Da y 1 7 6 visit of St u d y
A K 0 0 2- 0 1 6, w hic h will be c o nsi d ere d Da y 1 of St u d y A K 0 0 2- 0 1 6 X.
P atie nts e nteri n g t he e xte nsi o n st u d y b ut w h o ca n n ot start t he e xte nsi o n st u d y
1 da y aft er t he Da y 1 7 6 visit has occ urre d will re mai n i n t he m ai n st u d y u ntil
t h e y recei ve t he first d os e of st u d y dr u g i n t h e e xte nsi o n st u d y.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 1 5 of 9 9 
 
St u d y Desi g n c o nt. 
T he Da y 1 9 7 a n d Da y 2 2 5 mai n st u d y visits will occ ur if t he patie nt d oes n ot
e nr oll i n t h e e xte nsi o n st u d y pri or t o t h e s c he d ul e d date of t hese visits. A
pati e nt e nr olli n g i n t he e xte nsi o n st u d y pri or t o Da y 1 9 7 will n ot c o m plete t he
Da y 1 9 7 or Da y 2 2 5 pr oce d ures u n der t he mai n st u d y.
A patie nt n ot e nr olle d i n t he e xte nsi o n st u d y o n or bef ore Da y 2 2 5 will n ot be
a bl e t o e nt er t he e xte nsi o n st u d y.
P atie nts e nteri n g t he e xte nsi o n st u d y wit hi n 2 8 ( ± 3) da ys of t he l ast st u d y
visit i n A K 0 0 2- 0 1 6 will n ot re q uire d u pli cate pre d os e la bs or pr oce d ures pri or
t o t he first d osi n g i n A K 0 0 2- 0 1 6 X.
P atie nts will recei ve m o nt hl y i nf usi o ns of A K 0 0 2 a d mi nist ere d e ver y
2 8 ( ± 3) da ys i n a n o pe n-la bel ma n ner. All i nf usi o ns of A K 0 0 2 will be
a d mi nistere d at 3 m g/ k g.
A n E G D wit h bi o ps y will occ ur o n Da y 2 1 1 ( ± 3) a n d Da y 5 0 5 ( ± 3) or
2 8 ( ± 3) da ys after last d ose of st u d y dr u g if earl y ter mi nati o n ( E T).
P atie nts will be f oll o we d f or 8 4 ( ± 3) da ys after last d ose. F oll o w- u p safet y
visits will occ ur o n E xte nsi o n Da ys 5 1 2, 5 3 3, a n d 5 6 1 ( ± 3 da ys) or 3 5, 5 6,
a n d 8 4 ( ± 3) da ys after last d ose if E T fr o m t he st u d y. If o nl y 1 f oll o w- u p visit
is p ossi ble, t he E G D wit h bi o ps y a n d first safet y f oll o w- u p visit ( Da y 3 5 after
last d os e) m a y be c o m bi ne d. If a patie nt d oes n ot a gree t o ha v e t he earl y-
ter mi nati o n E G D, t he first safet y f oll o w- u p visit ( Da y 3 5 after l ast d ose)
s h o ul d still occ ur.
T he e xte nsi o n st u d y d oes n ot i ncl u de fasti n g re q uire me nts. Pati e nts
u n der we nt a sta n dar di ze d baseli n e e val uati o n of eati n g ha bits, f o o d
ha bits/restri cti o ns, a n d f o o d a v oi da nce be h a vi ors d uri n g St u d y A K 0 0 2- 0 1 6
a n d will be as ke d t o m ai ntai n t he s a m e diet t hr o u g h t he first 6 m o nt hs of t he
st u d y. After t h e s e ve nt h d ose has b ee n a d mi nistere d, diet a n d eati n g ha bits
ma y be li beralize d, as d esire d, wit h all c ha n ges n ot e d i n t he C R F.
Prest u d y me dicati o ns s h o ul d re m ai n u nc ha n g e d t hr o u g h o ut t he st u d y.
S yste mic or s wall o we d ster oi ds a b o ve 1 0 m g dail y pre d nis o ne ( or e q ui vale nt)
will n ot b e all o we d e xce pt as a n a p pr o v e d pre m e dicati o n pri or t o i nf usi o n, t o
treat a n I R R t hat occ urs d uri n g i nf usi o n, or t he use is d ue t o u nf oresee n
circ u msta nces w he n it is dee me d m e dicall y necessar y t o treat a n u nrelate d
me dical c o n diti o n.
Dail y a d mi nistrati o n of t he P R O q uesti o n naire (i ncl u di n g a n y a p pr o priat e
a d diti o nal q uesti o ns) t hr o u g h o ut t he st u d y a n d f oll o w- u p peri o d f or all
pati e nts.
T otal d urati o n of St u d y A K 0 0 2- 0 1 6 X will be a p pr o xi mat el y 2 1 m o nt hs.




Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 1 7 of 9 9 
 
P ati e nt S electi o n 
Criteri a c o nt. 
I n cl usi o n Criteri a c o nt. 
5)
Fe male pati e nts m ust b e eit her p ost m e n o pa us al f or at least 1 year or
s ur gicall y sterile (t u bal li gati o n, h ysterect o m y, or bilateral o o p h orect o m y)
f or at least 3 m o nt hs, or if of c hil d beari n g p ote ntial, ha ve a ne gati ve
pre g na n c y t est a n d a gree t o use d ual met h o ds of c o ntrace pti o n or a bstai n
fr o m se x ual acti vit y u ntil t h e e n d of t he st u d y or f or 1 2 0 da ys f oll o wi n g t he
last d os e of st u d y dr u g, w hi c he ver is l o n ger.
6)
Male p ati e nts wit h fe male part ners of c hil d beari n g p ote ntial m ust a gree t o
use a hi g hl y effecti ve m et h o d of c o ntrace pti o n ( v asect o m y is acce pta ble)
u ntil t h e e n d of t he st u d y or f or 1 2 0 da ys f oll o wi n g t h e last d ose of st u d y
dr u g, w hi c he ver is l o n ger. All fertil e m e n wit h fe m ale part ners of
c hil d beari n g p ote ntial s h o ul d be i nstr uct e d t o c o ntact t he I n vesti gat or
i m me diat el y if t he y s us pect t heir part n er mi g ht be pre g na nt at a n y ti me
d uri n g st u d y partici pati o n.
E xcl usi o n Criteri a 
P atie nts will be e xcl u de d fr o m t he st u d y if t h e y m eet a n y of t he f oll o wi n g criteri a:
1)
P o or t olera nce t o pre vi o us a d mi nistrati o n of A K 0 0 2 i n t h e o pi ni o n of t he
I n vesti gat or.
2)
K n o w n h y perse nsiti vit y t o a n y c o nstit ue nt of t he st u d y dr u g.
3)
A n y disease, c o n diti o n ( m e di cal or s ur gical), or car diac a b n or m alit y, w hi c h,
i n t he o pi ni o n of t he I n vesti gat or, w o ul d place t h e patie nt at i ncrease d ris k.
4)
Pla n ne d or e x pecte d vacci nati o n wit h li ve atte n uate d vacci nes d uri n g t h e
treat me nt, or vacci nati o n e x pecte d wit hi n 5 half-li v es ( 4 m o nt hs) of A K 0 0 2
a d mi nistrati o n.
All t y pes a n d f or m ulati o ns of vacci n es (i ncl u di n g li ve atte n uat e d vacci nes)
a ut h orize d b y F D A or ot her re g ulat or y a ut h orit y f or t he pre ve nti o n of
C O VI D- 1 9 ma y be a d mi nistere d bef ore, d uri n g, or after t his st u d y. T he
vacci ne s h o ul d n ot b e a d mi nistere d wit hi n 7 da ys pri or t o a n d wit hi n 7 da ys
after t h e a d mi nistrati o n of A K 0 0 2 s o t hat a n y si de effects ca us e d b y eit h er of
t h e 2 m e di cati o ns ca n be m ore easil y deter mi ne d.
5)
W o me n w h o are pre g na nt, breastfee di n g, or pla n ni n g t o bec o me pre g na nt
w hile partici pati n g i n t he st u d y.
6)
A n y ot her reas o n t hat i n t h e o pi ni o n of t he I n vesti g at or or Me di cal M o nit or
ma kes t he p ati e nt u ns uita ble f or e nr oll me nt.




Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 1 9 of 9 9 
 
S afet y E v al u ati o ns 
c o nt. 
A d diti o nal safet y e val uati o ns i ncl u de vit al si g ns, C B C wit h differe ntial, bl o o d 
c he mistr y, uri nal yses, s y m pt o mati c p h ysi cal e xa mi nati o ns, a n d a nti- dr u g 
a nti b o dies ( A D A) t o A K 0 0 2. 
P h a r m ac o d y n a mi c/ 
Effic ac y 
E v al u ati o ns 
Dail y self-a d mi nistrati o n of a dis ease-s pecific Patie nt Re p orte d O ut c o m e ( P R O) 
q uesti o n naire will be use d t o e val uat e si g ns a n d s y m pt o ms ass oci at e d wit h E G 
a n d/ or E o D. Pati e nt T otal S y m pt o m S c ore ( T S S) will be e val uate d, ca pt uri n g 
6 c o m m o n s y m pt o ms of E G/ E o D (a b d o mi nal pai n, na usea, a b d o mi n al cra m pi n g, 
l oss of a p petit e, f ull n ess bef ore fi nis hi n g a meal [earl y satiet y], a n d bl o ati n g). 
V o miti n g a n d di arr hea will als o be ca pt ure d b ut will n ot be i ncl u d e d i n t he T S S. 
F or patie nts wit h c o nc o mit a nt aller gi c ast h m a or at o pic der matitis, e val u ati o n will 
i n cl u de a q uesti o n f or eac h a b o ut t he s e verit y of s y m pt o ms o ver t he p ast 
2 4 h o urs. F or all patie nts t hat recei ve d t he d ys p ha gia q uesti o n d uri n g 
A K 0 0 2- 0 1 6, t he dail y e val u ati o n will als o i ncl u de a q uesti o n a b o ut t he se verit y of 
d ys p ha gi a o ver t he past 2 4 h o urs. 
P atie nts will rate t heir q ualit y of life usi n g t he n o n- disease-s pecific S F- 3 6 at 
vari o us st u d y visits. 
Bi o psi es of gastri c a n d d u o de nal m uc os a c ollecte d d uri n g pre-treat me nt a n d p ost-
treat me nt E G D will be e val u ate d f or n u m ber of e osi n o p hils. I n a d diti o n, t he
n u m b er of e osi n o p hils i n es o p ha geal m uc osa will be e val uat e d i n patie nts wit h 
c o nc o mit a nt E o E.
Bl o o d e osi n o p hil c o u nts will b e ass ess e d at eac h st u d y visit, pre d os e a n d 1 h o ur 
p ost d ose. 
P h a r m ac o ki n etic 
E v al u ati o ns 
Bl o o d (ser u m) will be c oll ecte d f or ass ess m e nt of A K 0 0 2 c o nce ntrati o n usi n g a 
vali dat e d e nz y me-li n ke d i m m u n os or be nt ass a y m et h o d. Bl o o d (s er u m) will be 
c ollecte d f or ass ess me nt of A K 0 0 2 A D A usi n g a vali dat e d assa y met h o d.  
T he P K a n d A D A bl o o d sa m ples will b e o btai ne d pre d ose o n E xt e nsi o n Da y 1 
(or  o btai ne d fr o m t he Da y 1 7 6, 1 9 7, or 2 2 5 e val uati o ns of St u d y A K 0 0 2- 0 1 6 if 
t h e patie nt e nt ers A K 0 0 2- 0 1 6 X) as well as o n E xt e nsi o n Da y 1 9 7 ( ± 3) a n d 
Da y 5 1 2 ( ± 3) or 3 5 ( ± 3) da ys after l ast d ose of st u d y dr u g if E T. 
I n a d diti o n, A D A bl o o d s a m ples s h o ul d be o bt ai n e d at a n y ti m e a n 
i m m u n o ge nicit y-relate d A E occ urs.
St atistic al A n al ysis 
S u m m ar y statistics will i n cl u de t he m ea n, m e di a n, st a n dar d de vi ati o n, mi ni m u m, 
a n d m a xi m u m f or c o nti n u o us varia bl es, a n d n u m ber a n d p erce nt a ge of patie nts 
f or cate g orical varia bles. N o i m p ut ati o n will be us e d f or missi n g data. Dat a will 
be a nal yze d as lai d o ut i n t he St atisti cal A nal ysis Pla n. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 0 of 9 9 
 
2.
B a c k gr o u n d
2. 1 
Si glec- 8 a n d A K 0 0 2 
Si glec- 8, a me m ber of t he C D 3 3-relate d fa mil y of sialic aci d- bi n di n g, i m m u n o gl o b uli n-li ke 
lecti ns ( Si glecs), is a tra ns me m bra ne cell s urface pr otei n wit h restricte d tiss ue distri b uti o n, 
e x presse d sele cti v el y o n t h e s urface of m at ure e osi n o p hils a n d mast cells, b ut n ot i n earl y 
prec urs ors of t hese cell p o p ulati o ns. Si glec- 8 c o ntai ns 3 e xtracell ular i m m u n o gl o b uli n-li ke 
d o mai ns, a tra ns me m bra ne re gi o n, a n d a c yt o plas mic tail c o ntai ni n g 2 t yr osi ne- base d si g nali n g 
m otifs, i ncl u di n g a n i m m u n orece pt or t yr osi ne- base d i n hi bit or y m otif wit h i n hi bit or y f u ncti o n. 
E n ga ge me nt of Si glec- 8 i n mast cells ca n res ult i n i n hi biti o n of me diat or r elease, a n d i n 
e osi n o p hils, ca n i n d uce a p o pt osis ( B oc h n er, 2 0 0 9). A K 0 0 2 als o s h o ws p ote nt a nti b o d y-
de pe n de nt cell ular c yt ot o xicit y ( A D C C) a gai nst e osi n o p hils i n vi v o a n d i n vitr o.  
2. 2  
O ver vie w of N o n cli nic al St u di es 
A K 0 0 2 is a h u ma nize d n o n-f uc os ylate d i m m u n o gl o b uli n G 1 (I g G 1) m o n ocl o nal a nti b o d y 
directe d a gai nst t he i n hi bit or y rece pt or Si glec- 8, a m e m ber of t h e C D 3 3-relate d f a mil y of 
Si glecs.  
Si glec- 8 has a restricte d tiss ue distri b uti o n, e x presse d selecti v el y o n t h e s urface of m at ure 
e osi n o p hils a n d mast cells, b ut n ot i n earl y prec urs ors of t hese cell p o p ulati o ns. I n bl o o d, bi n di n g 
of A K 0 0 2 t o Si glec- 8 i n d uces A D C C a gai nst e osi n o p hils, lea di n g t o ra pi d a n d s ustai ne d 
de pleti o n of t hese cells fr o m circ ulati o n. I n t h e tiss ue, A K 0 0 2 i n d uces direct a p o pt osis of 
e osi n o p hils a n d i n hi biti o n of mast cells. T his pr ofile of acti vit y ma y pr o vi de cli nical be nefit i n 
diseases i n w hic h t hese cell t y pes pla y a r ole, s uc h as e osi n o p hilic gastritis a n d e osi n o p hilic 
d u o de nitis. 
Si glec- 8 is n ot e x presse d i n s pecies ot her t ha n h u ma ns, a n d t heref ore, 2 n o vel m o use m o dels 
ha ve bee n de vel o pe d f or i n vi v o testi n g of A K 0 0 2. A K 0 0 2 has bee n st u die d i n Si glec- 8 
h u ma nize d a n d tra ns ge nic m o use m o dels a n d wit h h u ma n bl o o d a n d tiss ue cells. T he first m o del 
uses i m m u n o deficie nt mice ca pa ble of ge nerati n g h u ma n i m m u ne cells i ncl u di n g mast cells a n d 
e osi n o p hils w he n e n grafte d wit h h u ma n he mat o p oietic ste m cells. T he a bilit y of a nti- Si glec- 8 
a nti b o dies t o i n hi bit mast cell- me diate d reacti o ns h as bee n e val uate d i n t his m o del. T h e sec o n d 
r o de nt m o del is a tra ns g e nic m o use li ne t hat e x presses h u ma n Si glec- 8. T he e x pressi o n of 
Si glec- 8 o n t h e cell s urface i n t hese mice is restricte d t o e osi n o p hils, m ast cells, a n d bas o p hils, a 
patter n of s urface e x pressi o n e q ui vale nt t o t hat i n h u ma ns. A nti- Si glec- 8 a nti b o dies ca n pre ve nt 
I g E- me diate d a na p h yla xis i n t his tra ns ge ni c m o use li ne, i n dicati n g t hat Si glec- 8 is 
p har mac ol o gicall y acti ve i n t he m o del. T he a bilit y of A K 0 0 2 t o effect m ast cells a n d e osi n o p hils 
has bee n e val uate d i n t his m o del. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 1 of 9 9 
 
A K 0 0 2 i n hi bits I g E- me diate d m ast cell de gra n ulati o n a n d release of t he ne wl y f or me d me di at or 
pr osta gla n di n D 2 i n vitr o wit h o ut aff ecti n g mast cell via bilit y. I n peri p heral bl o o d pre parati o ns 
fr o m n or mal h u ma n d o n ors, A K 0 0 2 s h o ws selecti ve de pleti o n of e osi n o p hils. I m p orta ntl y, i n a 
w h ole- bl o o d c yt o ki ne-release ass a y usi n g i m m o bilize d A K 0 0 2 t o e n ha nce t h e p ote ntial f or 
a nti b o d y cr ossli n ki n g, A K 0 0 2 di d n ot lea d t o d ose- de pe n de nt release of pr o-i nfla m mat or y 
c yt o ki nes. 
T o e val u ate t he i n vi v o acti vit y of a nti- Si glec- 8 a nti b o dies i n a n i m m u n oc o m pete nt r o de nt 
m o del, a tra ns ge nic m o use strai n has bee n de vel o pe d t hat selecti vel y e x presses h u ma n Si glec- 8 
o n t he s urface of m o use mast cells, e osi n o p hils, a n d bas o p hils. I n si n gle- d ose a n d re peat- d ose 
st u dies i n Si glec- 8 tr a ns ge nic mice, A K 0 0 2 de m o nstrate d selecti ve de pleti o n of p erit o neal m ast 
cells a n d circ ulati n g a n d tiss u e (s plee n) e osi n o p hils a n d bas o p hils. 
I n 2 G o o d La b orat or y Practice ( G L P) t o xicit y a n d t o xic o ki netic st u dies, A K 0 0 2 w as well 
t olerate d at d oses of 5 0 m g/ k g a n d 1 0 0 m g/ k g, 5-f ol d a n d 1 0-f ol d, res pecti vel y, t h e le vel of t h e 
hi g hest d ose pr o p ose d t o be st u die d i n h u ma ns. A K 0 0 2 s h o we d s ustai ne d s yste mic e x p os ure i n 
Si glec- 8 tr a ns ge nic mice wit h a n e xte n d e d ter mi nal h alf-life esti m ate d as 2 7 2 h o urs or 3 3 7 h o urs 
f oll o wi n g si n gle I V a d mi nistrati o n of 5 0 m g/ k g or 1 0 0 m g/ k g, res pecti vel y. T h ere w as n o 
e vi de nce of a nti- dr u g a nti b o dies ( A D A) i n eit her st u d y. Decreases i n e osi n o p hil c o u nts i n b ot h 
se xes w ere o bser ve d, w hic h reflect t he e x pecte d p har mac ol o g y of A K 0 0 2. T he n o- o bser ve d-
a d verse-effect le vel ( N O A E L) f oll o wi n g I V a d mi nistrati o n of A K 0 0 2 t o tra ns ge ni c mice was 
1 0 0 m g/ k g, w hic h s u p p orts t he P h ase 1 st u dies i n h u ma ns.  
2. 3  
O ver vie w of Cli nic al St u dies 
A K 0 0 2, a d mi nistere d as a n i ntr a ve n o us i nf usi o n has bee n pre vi o usl y teste d i n healt h y v ol u nteers 
a n d i n patie nts wit h i n d ole nt s yste mic mast oc yt osis (I S M), c hr o nic urticaria ( C U), se vere aller gic 
c o nj u ncti vitis ( A C), mast cell gastritis, a n d e osi n o p hilic gastritis ( E G) a n d/ or e osi n o p hilic 
d u o de nitis ( E o D), w hic h was referre d t o as e osi n o p hilic gastr oe nteritis ( E G E) i n pre vi o us 
st u dies. 
M ulti ple d oses of 3 m g/ k g ha ve b ee n gi v e n t o patie nts wit h I S M, C U, se vere A C, E G, a n d/ or 
E o D. I n t hese st u dies, patie nts re p orte d i m pr o ve me nts i n disease s y m pt o ms wit h A K 0 0 2 
p har mac o d y na mic ( P D) acti vit y bei n g o bser ve d f or pr ol o n ge d peri o ds of ti me a n d A K 0 0 2 
p har mac o ki n etic ( P K) para meters de m o nstrati n g a half-life a me na ble t o a d mi nistr ati o n e ver y 
4 wee ks. 
T o date, healt h y v ol u nteers a n d patie nts wit h I S M, C U, se vere A C, E G/ E o D, e osi n o p hilic 
es o p ha gitis ( E o E), a n d mast cell g astritis ha ve bee n e nr olle d i n cli nical st u dies. I n ge neral, 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 2 of 9 9 
 
A K 0 0 2 has bee n well t olerate d. T he m ost c o m m o n treat me nt-e mer ge nt a d verse e ve nt ( T E A E) 
o bser ve d was i nf usi o n-relate d r eacti o n (I R R). M ost I R R were mil d t o m o derate a n d res ol ve d o n 
t heir o w n, wit h n o treat m e nt r e q uire d. I nf usi o n-relate d reacti o ns t hat were seri o us res ol ve d 
wit hi n a p pr o xi m atel y 2 4 h o urs. C o m m o n s y m pt o ms of I R R were hea dac he, na usea, s weati n g, 
fl us hi n g, a n d re d ness. M ost I R R occ urri n g d uri n g t he i nf usi o n c o ul d be ma na ge d b y sl o wi n g or 
te m p orar y i nterr u pti o n of t he i nf usi o n, wit h mi ni mal i nter ve nti o n. I n 6 healt h y v ol u nteers w h o 
recei v e d 2 d oses of 0. 3 m g/ k g A K 0 0 2, 4 wee ks a part, t h e sec o n d d ose was better t olerate d t h a n 
t he first d ose. T his is als o t he case i n patie nts wit h I S M, C U, se ver e A C, a n d E G/ E o D wit h fe wer 
a d verse e ve nts ( A E) re p orte d d uri n g t he sec o n d a n d s u bse q ue nt i nf usi o ns w he n c o m p are d t o t he 
first i nf usi o n. 
I n all st u dies t here was a tr a nsie nt decrease i n l y m p h oc yte c o u nt after t he A K 0 0 2 i nf usi o n 
( us uall y res ol vi n g wit hi n 1 da y) t hat was n ot ass o ciate d wit h a n y cli nical c o nse q ue nce a n d a 
s ustai ne d s u p pressi o n of e osi n o p hils t hat was c o nsiste nt wit h t he mec ha nis m of acti o n of A K 0 0 2. 
N o si g nifica nt tre n ds were o bser ve d f or c ha n ges i n vital si g ns, electr o car di o gra ms ( E C G), 
cli nical la b orat or y p ara meters, or p h ysical e xa mi nati o ns.  
I n t he ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, P hase 2 st u d y of A K 0 0 2 i n 6 5 patie nts wit h 
E G a n d/ or E o D, patie nts were ra n d o mize d t o recei ve m o nt hl y d oses of place b o, l o w d ose A K 0 0 2 
( 0. 3, 1, 1, a n d 1 m g/ k g), or hi g h d ose A K 0 0 2 ( 0. 3, 1, 3, a n d 3 m g/ k g) i n a 1: 1: 1 rati o 
(Dell o n, 2 0 2 0 ). All pri mar y a n d sec o n dar y e n d p oi nts were met i n t he st u d y. T here was a 9 7 % 
a n d 9 2 % mea n r e d ucti o n i n e osi n o p hils i n t h e st o mac h/ d u o de n u m f or t he hi g h d ose a n d l o w d ose 
A K 0 0 2-treate d patie nts, res pecti vel y, vers us a 1 0 % i n crease f or place b o-treate d patie nts 
( p < 0. 0 0 0 1). T h e re d ucti o n of e osi n o p hils was ass ociate d wit h a st atisticall y si g nifica nt re d ucti o n 
i n t otal s y m pt o m sc ore ( T S S) of 5 8 % i n t he hi g h d ose A K 0 0 2 gr o u p a n d 4 9 % re d ucti o n i n t he 
l o w d ose A K 0 0 2 gr o u p vers us a 2 4 % re d ucti o n i n t h e place b o gr o u p ( p = 0. 0 0 1 2 a n d p = 0. 0 1 5, 
res pecti vel y). I m pr o ve me nt i n s y m pt o ms was o bser ve d wit hi n 2 4 h o urs of t he first d ose of st u d y 
dr u g. I n a d diti o n, 7 0 % of hi g h d ose treat e d patie nts a n d 6 8 % of l o w d ose tr eate d patie nts were 
treat me nt res p o n ders ( defi ne d as > 3 0 % i m pr o ve me nt i n T S S a n d > 7 5 % re d ucti o n fr o m baseli n e 
i n tiss ue e osi n o p hils) vers us 5 % f or place b o-tr eate d patie nts ( p < 0. 0 0 0 1). 
A p pr o xi matel y 4 0 % of patie nts ha d c o nc o mita nt E o E. I n t h ose patie nts, a mea n re d ucti o n of 
9 5 % of e osi n o p hils/ h pf i n es o p ha geal bi o psies f or A K 0 0 2-treate d patie nts was o bser ve d vers us 
n o c ha n ge f or place b o-tr eate d patie nts. Als o, 1 3 of 1 4 A K 0 0 2-treate d pati e nts ( 9 3 %) were 
 place b o-tr eate d patie nts 
( 1 1 %). D ys p ha gia i m pr o ve d b y 5 3 % i n A K 0 0 2-tr eate d patie nts vers us 1 7 % i n place b o-treate d 
patie nts. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 3 of 9 9 
 
M ore t ha n 9 0 % of patie nts i n t he P h ase 2 st u d y electe d t o c o nti n ue i nt o a l o n g-ter m c o nti n uati o n 
st u d y. I n t hat st u d y, a starti n g d ose of 1 m g/ k g A K 0 0 2 was use d, f oll o we d b y s u bse q u e nt d oses 
of 3 m g/ k g A K 0 0 2. Pre me dicati o n of 8 0 m g pre d nis o ne was a d mi nistere d t he da y bef ore t h e first 
d ose a n d sec o n d d ose f or 2 0 of t he 5 8 patie nts d ose d. Usi n g t his pre me dicati o n re gi me n, n o I R R 
were o bser ve d o n t h e first i nf usi o n of t he e xt e nsi o n st u d y. 
A t otal of 3 8 patie nts ha ve bee n tr eate d f or at least 7 2 wee ks i n t he A K 0 0 2- 0 0 3 X e xte nsi o n 
st u d y. T he dr u g has bee n w ell t olerate d, a n d n o c o nsiste nt l o n g-ter m dr u g relate d A E ha ve bee n 
n ote d.  
2. 4  
E osi n o p hilic G astr oi ntesti n al Dis or ders 
E osi n o p hilic gastr oi ntesti nal dis or ders ( E GI D) are c hr o nic i nfla m mat or y dis or ders c haracterize d 
b y i nfiltrati o n of e osi n o p hils al o n g differe nt se g me nts of t he gastr oi ntesti nal tract, i n t he a bse nce 
of a n y ot her ca use of t h e e osi n o p hilia ( Cal d well, 2 0 1 4 ). 
E osi n o p hilic gastritis a n d/ or e osi n o p hilic d u o de nitis (f or merl y referre d t o as e osi n o p hilic 
gastr oe nteritis) re prese nt w hat are tra diti o nall y b elie ve d t o be rare t y pes of E GI D t hat are 
c haracterize d b y c hr o nic, ofte n se vere i nfla m mati o n d ue t o patc h y or diff use i nfiltrati o n of 
e osi n o p hils i nt o la yers of t he st o mac h, s mall i ntesti ne, or b ot h t he st o mac h a n d s mall i ntesti ne 
(Pr ussi n, 2 0 1 4 ; Ree d, 2 0 1 5 ; Z ha n g, 2 0 1 7 ). T he dia g n osis is base d o n cli nical prese ntati o n 
( gastr oi ntesti nal s y m pt o ms) c o m bi ne d wit h i ncrease d tiss ue e osi n o p hils i n bi o ps y s peci me ns 
fr o m t h e st o mac h a n d/ or d u o de n u m wit h o ut a n y ot her ca use f or t h e e osi n o p hilia. I n v ol ve me nt of 
t he s mall i ntesti ne is t y picall y assesse d b y perf or mi n g d u o de nal bi o psies usi n g a n es o p ha g o-
gastr o- d u o de n os c o p y ( E G D) a n d has bee n referre d t o as e osi n o p hilic gastr oe nteritis or 
e osi n o p hilic e nteritis, t h o u g h e osi n o p hilic d u o de nitis is m ore a p pr o priate. T he gastr oi ntesti nal 
s y m pt o ms are belie ve d t o be d ue t o t he release of i nfla m mat or y me diat ors fr o m acti vate d 
e osi n o p hils, a n d li kel y mast cells. S y m pt o ms t hat are ofte n se vere a n d de bilitati n g c o m m o nl y 
i ncl u de a b d o mi nal pai n, na usea, bl o ati n g, earl y satiet y, f ull n ess bef ore fi nis hi n g a meal, 
a b d o mi nal cra m pi n g, v o miti n g, diarr hea, a n d wei g ht l oss ( Al h m o u d, 2 0 1 6 ; L o pez- Me di n a, 2 0 1 5 ; 
Ma ns o or, 2 0 1 7 ; Ree d, 2 0 1 5 ).
Je nse n (2 0 1 6 ) esti mate d t he pre vale nce of E G a n d E o D t o be 6. 3/ 1 0 0, 0 0 0 a n d 8. 4/ 1 0 0, 0 0 0 
res pecti vel y (f or patie nts a ges 1 – 6 4 years ol d). Ma ns o or ( 2 0 1 7) esti mate d t he o verall pre vale nce 
of E G t o be 5. 1/ 1 0 0, 0 0 0 pers o ns. 
Patie nts ma y als o ha ve c o nc o mita nt at o pic diseases li ke f o o d aller g y, ast h ma, a n d at o pic 
der matitis, w hic h f urt her i m pact q ualif y of life a n d c o ntri b ute t o healt h care c osts. A d diti o nall y, 
8 % t o 1 0 % of patie nts ha ve c o nc o mita nt E o E (Je nse n, 2 0 1 6). 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 4 of 9 9 
 
T here are n o F D A-a p pr o ve d tr eat m e nts f or E G a n d/ or E o D. C urre nt t hera pies a n d disease 
ma na ge me nt i ncl u de dietar y restricti o n/eli mi nati o n, pr ot o n p u m p i n hi bit ors ( P PI), 
a nti hista mi nes, s yste mic or t o pical c ortic oster oi ds, a n d occasi o nal off-la bel use of 
i m m u n o m o d ulat or y bi ol o gics ( Pr ussi n, 2 0 1 4; Ree d, 2 0 1 5; Z ha n g, 2 0 1 7). Pr ot o n p u m p i n hi bit ors 
ha ve little t o n o be nefit i n patie nts wit h E G a n d/ or E o D des pite re p orts of pr o vi di n g partial 
be nefit i n s o me patie nts wit h E o E ( Katz, 2 0 1 3 ). Restricte d/ ele me ntal diets are n ot effecti ve l o n g-
ter m treat me nt as t he y re q uir e strict c o m plia nce a n d, i n t h e case of ele me ntal diets, are e x pe nsi ve 
a n d are ofte n n ot rei m b urse d b y i ns ura nce. I n a d diti o n, c o m plia nce is ver y p o or, a n d pati e nt 
q ualit y of life is greatl y i m pacte d ( Be dell, 2 0 1 8 ; Peters o n, 2 0 1 3 ; Wec hsl er, 2 0 1 4 ). 
C ortic oster oi ds, s yste mic or s wall o we d, ha ve bee n s h o w n t o pr o vi de s y m pt o m relief b ut are n ot 
a p pr o priate f or l o n g-ter m treat me nt d ue t o n u mer o us si de effects a n d ass ociate d ris ks i n cl u di n g 
a dre nal i ns ufficie nc y, b o ne de mi n eralizati o n, i ncrease d c ha nce of i nfecti o n, oste o p or osis, 
be ha vi oral iss ues, a n d wei g ht gai n. 
B y mar ke dl y re d uci n g t h e n u m b er of bl o o d a n d tiss ue e osi n o p hils a n d i n hi biti n g t h e acti v ati o n of 
mast cells, A K 0 0 2 m a y be usef ul i n t h e tr eat m e nt of patie nts wit h E G a n d/ or E o D. T his pre mise 
is s u p p orte d b y t he P hase 2 data wit h A K 0 0 2 t hat s h o w si g nifica nt i m pr o ve me nt i n hist ol o g y a n d 
s y m pt o ms i n t h ese patie nts. 
Gi ve n t here are n o a p pr o ve d t h era pies f or t hese c hr o nic a n d de bilitati n g diseases, better 
treat me nt o pti o ns are clearl y nee de d t o ma na ge E G a n d E o D. 
3.
R ati o n ale f or St u d y a n d D ose Selecti o n
Base d o n e x perie nce wit h A K 0 0 2 i n healt h y v ol u nteers a n d i n patie nts wit h I S M, C U, se vere
A C, a n d E G/ E o D, t he pr o p ose d A K 0 0 2 d ose re gi me n of 1 8 t otal d oses is 3 m g/ k g a d mi nistere d
e ver y 4 wee ks. T o date, a ra n ge of A K 0 0 2 d oses fr o m 0. 0 0 0 3 m g/ k g t o 1 0 m g/ k g ha ve bee n
teste d, a n d t he ma xi m u m t olerate d d ose ( M T D) has n ot bee n r eac he d.
I n t he d o u ble- bli n d, place b o-c o ntr olle d P hase 2 st u d y i n patie nts wit h E G a n d/ or E o D, 2 d ose 
le vels wer e e val u ate d: a l o wer d ose re gi me n ( 4 m o nt hl y d oses of A K 0 0 2 at 0. 3, 1, 1, a n d 
1 m g/ k g) a n d a hi g her d ose re gi m e n ( 4 m o nt hl y d oses of 0. 3, 1, 3, a n d 3 m g/ k g). B ot h re gi me ns 
pr o d uce d dra matic re d ucti o n i n tiss ue e osi n o p hils a n d w ere ass ociate d wit h s u bsta ntial 
i m pr o ve me nt i n s y m pt o ms. H o we v er, n u mericall y greater i m pr o ve me nts were o bser ve d i n t he 
hi g h d ose ar m c o m pare d wit h t he l o w d ose ar m. 
As t here were n o differe nces i n safet y or t olera bilit y bet wee n t h e 2 d osi n g re gi me ns a n d t h e 
hi g her re gi me n a p p eare d t o be m ore effecti v e, t h e 3 m g/ k g d ose was selecte d f or t his P hase 3 
o pe n-la bel e xte nsi o n st u d y. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 5 of 9 9 
 
T he i nf usi o ns w ere ge nerall y well t olerate d at all d oses wit h m ost I R R bei n g mil d t o m o derate 
a n d ver y fe w A E o utsi d e t he i nf usi o n wi n d o w. Patie nts wit h I S M, C U, se vere A C, mast cell 
gastritis, a n d E G/ E o D ha ve recei ve d m o nt hl y d oses of 1 m g/ k g a n d 3 m g/ k g A K 0 0 2. S u bse q ue nt 
i nf usi o ns i n m ulti ple d ose c o h orts were ass ociate d wit h fe wer I R R w he n c o m p are d wit h t he first 
i nf usi o n. 
4.
St u d y O bjecti ves
T he o bjecti v e of t h e st u d y is t o ge nerate o pe n-la bel, l o n ger-ter m safet y, t olera bilit y, a n d efficac y
f oll o w- u p data i n patie nts wit h E G a n d/ or E o D w h o c o m plete d St u d y A K 0 0 2- 0 1 6 or St u d y
A K 0 0 2- 0 1 2. I n a d diti o n, t his st u d y pr o vi des p atie nts ra n d o mize d t o place b o i n A K 0 0 2- 0 1 6 t he
o pti o n t o recei v e acti v e d osi n g.
5.
St u d y Desi g n
5. 1  
St u d y O ver vie w 
T his is a P h ase 3, m ultice nter, o pe n-la bel, e xte nsi o n st u d y t o e val uate t he safet y a n d t olera bilit y 
of A K 0 0 2 i n patie nts wit h E G a n d/ or E o D. 
Patie nts w h o c o m plete St u d y A K 0 0 2- 0 1 6 or St u d y A K 0 0 2- 0 1 2 will ha ve t he o pti o n t o recei ve 
A K 0 0 2 i n a n o pe n-la bel ma n ner. A patie nt is cate g orize d as ha vi n g c o m plete d St u d y A K 0 0 2- 0 1 6 
if 6 i nf usi o ns of st u d y dr u g are a d mi nistere d a n d t he patie nt is f oll o we d t hr o u g h at least Da y 1 7 6 
( ± 3 da ys). A patie nt is cate g orize d as ha vi n g c o m plete d St u d y A K 0 0 2- 0 1 2 if t h e patie nt recei v e d 
all c o h ort-a p pr o priate d oses a n d was f oll o we d f or 5 m o nt hs after last d ose of st u d y dr u g i n 
A K 0 0 2- 0 1 2. D uri n g St u d y A K 0 0 2- 0 1 6 X, patie nts will m ai ntai n t he sa me patie nt n u m ber t hat 
was assi g ne d i n St u d y A K 0 0 2- 0 1 6 or St u d y A K 0 0 2- 0 1 2, as a p plica ble.  
Safet y will be assess e d b y b o d y wei g ht, vital si g ns, s y m pt o m- directe d p h ysical e xa mi nati o n, 
c o m plete bl o o d c o u nt ( C B C) wit h differe nti al, bl o o d c he mistr y, uri nal ysis, a n d assess me nt of A E
i ncl u di n g a d verse e ve nts of s pecial i nterest ( A E SI) a n d seri o us a d verse e ve nts ( S A E). I n 
a d diti o n, bl o o d sa m ples will be o btai ne d f or e val uati o n of P K a n d A D A.  
T he st u d y is d esi g ne d as f oll o ws: 
Patie nts c o m pleti n g St u d y A K 0 0 2- 0 1 6 d osi n g a n d e nteri n g t he e xte nsi o n st u d y ma y be gi n
e xte n de d d osi n g 1 da y after t he D a y 1 7 6 visit of St u d y A K 0 0 2- 0 1 6, w hic h will be
c o nsi dere d E xte nsi o n Da y 1 of St u d y A K 0 0 2- 0 1 6 X.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 6 of 9 9 
 
Patie nts e nteri n g t h e e xte nsi o n st u d y b ut w h o ca n n ot start t he e xte nsi o n st u d y 1 da y after
t he Da y 1 7 6 visit has occ urre d will re mai n i n t h e mai n st u d y u ntil t he y recei ve t he first d ose
of st u d y dr u g i n t he e xte nsi o n st u d y.
T he Da y 1 9 7 a n d Da y 2 2 5 mai n st u d y visits will occ ur if t he pati e nt d oes n ot e nr oll i n t he
e xte nsi o n st u d y pri or t o t he sc he d ule d date of t hese visits. A patie nt e nr olli n g i n t he
e xte nsi o n st u d y pri or t o Da y 1 9 7 will n ot c o m plete t he Da y 1 9 7 or Da y 2 2 5 pr oce d ures
u n der t he mai n st u d y.
A pati e nt n ot e nr olle d i n t he e xte nsi o n st u d y o n or bef ore Da y 2 2 5 i n t he A K 0 0 2- 0 1 6 st u d y
will n ot be a ble t o e nt er t he e xte nsi o n st u d y.
Patie nts e nteri n g t h e e xte nsi o n st u d y wit hi n 2 8 ( ± 3) da ys of t he last st u d y visit i n
A K 0 0 2- 0 1 6 will n ot re q uire d u pli cate pre d ose la bs or pr oce d ures pri or t o t he first d osi n g i n
A K 0 0 2- 0 1 6 X.
Patie nts will recei ve u p t o 1 8 i nf usi o ns of A K 0 0 2 a d mi nistere d e ver y 2 8 ( ± 3) da ys i n a n
o pe n-la bel ma n ner. All i nf usi o ns of A K 0 0 2 will be a d mi nistere d at 3 m g/ k g.
A n E G D wit h bi o ps y will o cc ur o n D a y 2 1 1 ( ± 3) a n d Da y 5 0 5 ( ± 3) or 2 8 ( ± 3) da ys after
last d ose of st u d y dr u g if earl y ter mi n ati o n ( E T).
Patie nts will be f oll o we d f or 8 4 ( ± 3) da ys after last d ose. F oll o w- u p safet y visits will occ ur
o n E xte nsi o n Da ys 5 1 2, 5 3 3, a n d 5 6 1 ( ± 3 da ys) or 3 5, 5 6, a n d 8 4 ( ± 3) d a ys after last d ose if
E T fr o m t he st u d y. If o nl y 1 f oll o w- u p visit is p ossi ble, t he E G D wit h bi o ps y a n d first
safet y f oll o w- u p visit ( Da y 3 5 after last d ose) ma y be c o m bi ne d. If a patie nt d oes n ot a gree
t o ha ve t he earl y-ter mi nati o n E G D, t h e first safet y f oll o w- u p visit ( Da y 3 5 after last d ose)
s h o ul d still occ ur.
T he e xt e nsi o n st u d y d oes n ot i ncl u de fasti n g r e q uire me nts, e xce pt f or t h ose re q uire d f or t he
c o n d uct of E G D. Patie nts u n der we nt a sta n dar dize d baseli ne e val uati o n of eati n g ha bits,
f o o d ha bits/r estri cti o ns, a n d f o o d a v oi da nce be ha vi ors d uri n g St u d y A K 0 0 2- 0 1 6 a n d will be
as ke d t o mai ntai n t he sa me diet t hr o u g h t he first 6 m o nt hs of t h e st u d y. After t he se ve nt h
d ose has b ee n recei ve d, diet a n d eati n g ha bits ma y be li beralize d, as desir e d, wit h all
c ha n ges t hat occ ur n ote d i n t he C R F.
Prest u d y me dicati o ns s h o ul d re mai n u nc ha n ge d t hr o u g h o ut t he st u d y. S yste mic or
s wall o we d ster oi ds a b o ve 1 0 m g dail y pre d nis o ne ( or e q ui vale nt) will n ot b e all o we d
e xce pt as a n a p pr o ve d pre me dicati o n pri or t o i nf usi o n, t o tr eat a n I R R t hat occ urs d uri n g
i nf usi o n, or t he use is d ue t o u nf oresee n circ u msta nces w he n it is dee me d me dicall y
necess ar y t o treat a n u nrelate d me dical c o n diti o n.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 2 7 of 9 9 
 
Dail y a d mi nistrati o n of t h e P R O q uesti o n naire (i ncl u di n g a n y a p pr o priate a d diti o nal
q uesti o ns) t hr o u g h o ut t he st u d y a n d t he f oll o w- u p peri o d f or all patie nts.
T otal d urati o n of St u d y A K 0 0 2- 0 1 6 X will be a p pr o xi matel y 2 1 m o nt hs.
5. 2 
S c he d ul e of E ve nts
T he o verall sc he d ule of pr oce d ures a n d assess me nts are de pi cte d i n T a ble 1 . 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d me nt 2 
Dat e: 2 3 Mar 2 0 2 2  
All a k os I nc.
Pa ge 2 8 of 9 9 
T a ble 1 
Sc he d ule of Assess me nts 
E xte nsi o n Tre at me nt Peri o d ( 1 8 m o nt hs)
E xte nsi o n F oll o w- U p Pe ri o d ( 1 2 wee ks)
Assess me nts
P ri or t o 
Fi rst 
D ose  
D os e 1
D os es 2 – 7 
D ose 8
D a y 2 1 1
D os es 9 – 1 8 
E G D
F oll o w- u p
F oll o w- u p
# 1
F oll o w- u p
# 2
F oll o w- u p
# 3
E xt e nsi o n 
Da y 1  
Da y 2 9, 5 7, 
8 5, 1 1 3, 1 4 1, 
1 6 9 ( ± 3 da ys)  
Da y 1 9 7 
( ± 3 d a ys) 
( ± 3 d a ys) 
Da y 2 2 5, 2 5 3, 
2 8 1, 3 0 9, 3 3 7, 
3 6 5, 3 9 3, 4 2 1, 
4 4 9, 4 7 7 
( ± 3 d a ys) 
Da y 5 0 5 
( ± 3 d a ys) 
or 2 8 da ys 
after l ast d ose 
if E T 
Da y 5 1 2 
( ± 3 d a ys) 
or 3 5 da ys 
after l ast d ose 
if E T 
Da y 5 3 3 
( ± 3 d a ys) 
or 5 6 da ys 
after l ast d ose 
if E T 
Da y 5 6 1 
( ± 3 d a ys) 
or 8 4 da ys 
after l ast d ose 
if E T 
I nf or me d c o nse nt 
X 
Me dical Hist or y
1
X 
Pri or/ C o nc o mita nt Me di cati o ns 2
X 3
X 
X 
X 
X 
X 
X 
X 
X 
Baseli ne Diet Assess me nt/ 
C o m plia nce 
X 3
X 
X 
X 
X 
X 
X 
B o d y wei g ht 4  
X ( pre d ose)3
X ( pre d os e)
X ( pre d os e)
X ( pre d os e)
X
X
X
Vit al si g ns 5
X 
X 
X 
X 
X 
X 
X 
S y m pt o m- directe d P h ysi cal E xa m 6
X 3
X 
X 
X 
X 
X 
X 
Eli gi bilit y assess me nt
X
X
e P R O Trai ni n g a n d Acti vati o n 7
X
e P R O Q uesti o n naire ( m a y i ncl u de 
a d diti o nal q uesti o ns) 8
<---------------------------- Perf or m dail y fr o m Da y 1 t hr o u g h Da y 5 6 1 or 8 4 da ys after last d ose, if E T------------------------------ > 
S F- 3 6 Healt h S ur ve y 9
X 3
X 
X 
X 
X 
X 
X 
D ys p ha gia Q uesti o n
< -------------------------- Perf or m dail y fr o m Da y 1 t hr o u g h Da y 5 6 1 or 8 4 da ys aft er last d ose, if E T------------------------------- > 
Di pstic k Pre g na nc y T est 1 0
X 3 ( pre d ose)
X ( pre d os e)
X ( pre d os e)
X ( pre d os e)
X
Access I R T t o e nter Patie nt I D a n d 
c urre nt b o d y wei g ht 1 1
X ( pre d os e)
X ( pre d os e)
X ( pre d os e)
X ( pre d os e)
Pre me dicati o n: pre d nis o ne 1 2
X 2 1
St u d y dr u g a d mi nistrati o n 1 3
X 2 2
X 
X 
X 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d me nt 2 
Dat e: 2 3 Mar 2 0 2 2  
All a k os I nc.
Pa ge 2 9 of 9 9 
T a ble 1 
Sc he d ule of Assess me nts c o nt. 
E xte nsi o n Tre at me nt Peri o d ( 1 8 m o nt hs)
E xte nsi o n F oll o w- U p Pe ri o d ( 1 2 wee ks)
Assess me nts
P ri or t o 
Fi rst 
D ose  
D os e 1
D os es 2 – 7 
D ose 8
D a y 2 1 1
D os es 9 – 1 8 
E G D
F oll o w- u p
F oll o w- u p
# 1
F oll o w- u p
# 2
F oll o w- u p
# 3
E xt e nsi o n 
Da y 1  
Da y 2 9, 5 7, 
8 5, 1 1 3, 1 4 1, 
1 6 9 ( ± 3 da ys)  
Da y 1 9 7 
( ± 3 d a ys) 
( ± 3 d a ys) 
Da y 2 2 5, 2 5 3, 
2 8 1, 3 0 9, 3 3 7, 
3 6 5, 3 9 3, 4 2 1, 
4 4 9, 4 7 7 
( ± 3 d a ys) 
Da y 5 0 5 
( ± 3 d a ys) 
or 2 8 da ys 
after l ast d ose 
if E T 
Da y 5 1 2 
( ± 3 d a ys) 
or 3 5 da ys 
after l ast d ose 
if E T 
Da y 5 3 3 
( ± 3 d a ys) 
or 5 6 da ys 
after l ast d ose 
if E T 
Da y 5 6 1 
( ± 3 d a ys) 
or 8 4 da ys 
after l ast d ose 
if E T 
Bl o o d f or C B C wit h differe nti al 1 4, 1 5
X 
X 
X 
X 
X 
X 
X 
Bl o o d f or c he mistr y 1 4, 1 6
X ( pre d ose) 3
X ( pre d ose) 
X ( pre d ose) 
X ( pre d ose) 
X 
X 
X 
Uri nal ysis 1 4, 1 7
X ( pre d ose) 3
X ( pre d ose) 
X 
Bl o o d f or p har mac o ki netics 1 4, 1 8
X ( pre d ose) 3
X ( pre d ose)
X
Bl o o d f or A D A 1 4, 1 9
X ( pre d ose) 3
X ( pre d ose) 
X 
Bl o o d f or T ot al Ser u m I g E 1 4, 2 0
X ( pre d ose) 3
X 
E G D wit h bi o ps y 2 3
X
X
N o n-seri o us a d verse e ve nts 2 4
X 
X 
X 
X 
X 
X 
X 
X 
X 
A d verse e ve nts of s p ecial i nt erest 2 5
X 
X 
X 
X 
X 
X 
X 
X 
X 
Seri o us a d verse e ve nts 2 6
X 
X 
X 
X 
X 
X 
X 
X 
X 
C B C: C o m plete Bl o o d C o u nt
E G D: Es o p ha g o- Gastr o- D u o de n osc o p y 
E T: E arl y Ter mi nati o n
I R T: I nt eracti ve Res p o nse T ec h n ol o g y
T a ble N otes 
1)
Rec or d all perti ne nt, o n g oi n g m e dic al hist or y as well as a n y si g nifica nt a d verse e v e nts ( A E) t hat occ urre d i n t he A K 0 0 2- 0 1 6 or A K 0 0 2- 0 1 2 st u d y b ut res ol ve d b ef ore t he first
d ose i n t he e xte nsi o n st u d y.
2)
Rec or d all c o nc o mita nt me di cati o ns t a ke n wit hi n 3 0 d a ys of E xte nsi o n Da y 1 a n d d uri n g t he c o urse of t he st u d y. Re c or d all c o nc o mita nt me dicati o n re cei ve d d uri n g E G D, a n y
pre me di cati o n gi ve n, a n d a n y me dicati o n use d f or t he treat me nt of I R R.
3)
D o n ot c ollect if pr oc e d ure was perf or me d as part of t he last st u d y visit i n A K 0 0 2- 0 1 6 ( o n Da y 1 7 6, 1 9 7 or 2 2 5, de pe n di n g o n w he n pati e nt recei ves first d ose i n
A K 0 0 2- 0 1 6 X). Differe ntial cell c o u nts c ollect e d f or St u d y A K 0 0 2- 0 1 6 will n ot be u n bli n de d. T he A K 0 0 2- 0 1 6 X p ost d ose C B C wit h differe ntial is still re q uire d 1 h o ur
( ± 1 5 mi n ut es) after t he first A K 0 0 2- 0 1 6 X i nf usi o n e n ds.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d me nt 2 
Dat e: 2 3 Mar 2 0 2 2  
All a k os I nc.
Pa ge 3 0 of 9 9 
T a ble N otes c o nt. 
4)
B o d y wei g ht will be meas ure d pre d ose a n d rec or d e d i n kil o gra ms ( k g) o n Da y 1, all i nf usi o n da ys, a n d at F oll o w- u p visits o n Da ys 5 1 2, 5 3 3, a n d 5 6 1 or 3 5 ( ± 3), 5 6 ( ± 3), a n d
8 4 ( ± 3) da ys after last d ose of st u d y dr u g if E T. B o d y wei g ht is t o b e meas ure d i n k g as it is use d t o deter mi ne patie nt d osi n g calc ulati o ns
5)
Vit al si g ns i ncl u di n g s yst oli c a n d di ast olic bl o o d press ure, p ulse, b o d y te m perat ure, a n d res pirat or y rate will be t a ke n afte
 mi n ut es a n d
bef ore a n y bl o o d dra w. Vit al si g ns will be meas ure d o n all d osi n g da ys wit hi n 3 0 mi n utes pre d ose, wit hi n 3 0 mi n utes aft er t he start of i nf usi o n, a n d wit hi n 3 0 mi n utes
f oll o wi n g t he e n d of i nf usi o n.
6)
A s y m pt o m- directe d p h ysical e xa mi nati o n (i ncl u di n g assess me nt of p ossi ble i nf usi o n sit e reacti o ns) will be perf or me d b y t he I n vesti gat or or desi g nee, as ne e de d if a n y
si g nifica nt s y m pt o ms or c ha n ges fr o m baseli ne are re p orte d.
7)
Acti vate P R O q uesti o n naire a n d pr o vi d e patie nt wit h u ni q ue user na m e a n d pass w or d. Use e P R O T eac hi n g T o ol f or patie nt trai ni n g a n d refere nce. P R O q uesti o n naire s h o ul d
be a cti vate d f or all patie nts o n Da y 1.
8)
T he P R O s h o ul d be c o m pl ete d b y t he patie nt, ar o u n d t he sa m e ti me eac h da y usi n g Vie d oc M E electr o nic p ortal. Patie nts wit h c o nc o mita nt hist or y of ast h ma a n d/ or at o pic
der matitis s y m pt o ms will recei ve a n e xtra q uesti o n a b o ut e ac h, as a p pr o priate. If t he d ys p ha gi a q uesti o n was p o p ulate d i n A K 0 0 2- 0 1 6, it will c o nti n ue t o p o p ul at e i n t h e dail y
Vie d oc M E q uesti o ns f or A K 0 0 2- 0 1 6 X. T he P R O ma y be c o m plete d via pa per if electr o ni c access is n ot p ossi bl e.
9)
C o m pl ete d i n cli ni c b y t he patie nt (c o m pl ete pri or t o bl o o d dra w, p h ysic al e xa mi n ati o n, or vit al si g n m eas ure me nts) d uri n g st u d y visits, usi n g Vie d oc M E electr o ni c p ort al.
Ma y be c o m plete d via pa per if ele ctr o ni c ac cess is n ot p ossi bl e.
1 0)
A s m all a m o u nt of uri ne c ollecte d f or uri nal ysis will be use d f or di pstic k pre g na nc y test (f or w o me n of c hil d beari n g a bilit y) pre d ose o n all i nf usi o n da ys a n d o n Da y 5 1 2 ( ± 3)
or 3 5 ( ± 3) da ys after l ast d ose if E T. Test kits will be s u p plie d b y t he c e ntral la b orat or y. Tests will be c o m plete d o n site a n d e val uat e d pri or t o i nf usi o n.
1 1) E n d p oi nt I R T t o be use d t o assi g n kit n u m bers f or eac h patie nt d osi n g. C urre nt patie nt b o d y wei g ht (t a ke n da y bef ore i nf usi o n or da y of i nf usi o n) will be e nt ere d i nt o I R T a n d
a m o u nt of A K 0 0 2 t o be mi xe d wit h 0. 9 % Na Cl will be cal c ulate d via E n d p oi nt.
1 2)
All pati e nts will self-a d mi nister 8 0 m g oral pre d nis o ne 1 2 – 2 4 h o urs pri or t o t he first i nf usi o n. A n a p pr o ve d alt er nati ve(s) m a y be use d wit h t he a p pr o val of t he Me dical
M o nit or. Pre m e dicati o n ma y be a d mi nistere d pri or t o s u bse q ue nt i nf usi o ns at t he I n vesti gat or’s discreti o n, b ut o nl y wit h writte n a p pr o val fr o m t h e Me di cal M o nit or.
1 3) St u d y dr u g will be a d mi nistere d as a si n gl e peri p heral I V i nf usi o n o ver at l east a 4- h o ur peri o d f or D ose 1. Sec o n d a n d s u bse q ue nt i nf usi o ns ca n be gi ve n o ver at l east a 2- h o ur
peri o d, de pe n di n g o n pri or i nf usi o n t olera bilit y. After t he si xt h i nf usi o n a 1- h o ur i nf usi o n sc he d ul e ma y be use d. Refer t o t he P har m ac y Ma n ual.
1 4) S peci me n pr ocesse d b y ce ntral la b orat or y. See ce ntral l a b orat or y ma n ual f or c oll ecti o n a n d pr ocessi n g det ails.
1 5)
Bl o o d f or C B C wit h differe nti al, i ncl u di n g a bs ol ute bl o o d e osi n o p hil c o u nt, will be o btai ne d j ust pri or t o eac h i nf usi o n, 1 h o ur ( ± 1 5 mi n utes) after t he e n d of eac h i nf usi o n as
well as o n E xt e nsi o n Da ys 5 1 2, 5 3 3, a n d 5 6 1 ( ± 3 da ys) or 3 5, 5 6, a n d 8 4 ( ± 3) da ys after last d ose of st u d y dr u g if E T.
1 6)
Bl o o d f or C he mistr y will be o bt ai ne d j ust pri or t o e ac h i nf usi o n as well as o n E xt e nsi o n Da ys 5 1 2, 5 3 3, a n d 5 6 1 ( ± 3) or 3 5, 5 6, a n d 8 4 ( ± 3) da ys aft er last d ose of st u d y dr u g
if E T.
1 7)
Uri n e f or Uri nal ysis will be c oll ecte d o n E xte nsi o n Da ys 1, 1 9 7 ( ± 3), a n d 5 1 2 ( ± 3) or 3 5 ( ± 3) da ys aft er last d ose of st u d y dr u g if E T.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d me nt 2 
Dat e: 2 3 Mar 2 0 2 2  
All a k os I nc.
Pa ge 3 1 of 9 9 
T a ble N otes c o nt. 
1 8)
Bl o o d f or P K will be c oll ecte d o n E xte nsi o n Da ys 1, 1 9 7 ( ± 3), a n d 5 1 2 ( ± 3) or 3 5 ( ± 3) da ys after last d ose of st u d y dr u g if E T.
1 9)
Bl o o d f or A D A will be c ollecte d o n E xte nsi o n Da ys 1, 1 9 7 ( ± 3), a n d 5 1 2 ( ± 3) or 3 5 ( ± 3) da ys after last d ose of st u d y dr u g if E T. A D A will als o be c oll ect e d w he n a n
i m m u n o ge nicit y-relate d A E occ urs.
2 0)
Bl o o d f or T ot al Ser u m I g E will be c olle cte d o n E xte nsi o n Da y 1 a n d E xte nsi o n Da y 5 1 2 ( ± 3) or 3 5 ( ± 3) da ys aft er last d ose of st u d y dr u g if E T.
2 1) T he c o nse nt f or m f or A K 0 0 2- 0 1 6 X m ust be si g ne d pri or  t o t he pati e nt t a ki n g pre d nis o ne pre me dic ati o n f or t he A K 0 0 2- 0 1 6 X st u d y.
2 2) T he fi nal E G D a n d Da y 1 7 6 he mat ol o g y assess me nt (first safet y f oll o w- u p) f or A K 0 0 2- 0 1 6 m ust  be c ollecte d pri or  t o t he patie nt ta ki n g pre d nis o ne pre m e dicati o n f or
A K 0 0 2- 0 1 6 X. T heref ore, d osi n g i n A K 0 0 2- 0 1 6 X m ust ta k e pl ace at l east 1 da y aft er c o m pleti o n of t he Da y 1 7 6 visit f or A K 0 0 2- 0 1 6.
2 3) See A p pe n di x 6 f or bi o ps y assess me nts. E G D s h o ul d occ ur o n Da y 2 1 1 ( ± 3) a n d Da y 5 0 5 ( ± 3) or 2 8 ( ± 3) da ys after l ast d ose of st u d y dr u g if t he patie nt disc o nti n ues t he st u d y
earl y a n d a grees t o ha ve a n e arl y ter mi nati o n bi o ps y.
2 4)
N o n-seri o us A E will be ca pt ure d fr o m Da y 1 (first d ose of st u d y dr u g) t hr o u g h Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) da ys after l ast d ose of st u d y dr u g if E T.
2 5)
A d verse e ve nts of s pecial i nt erest will be ca pt ure d fr o m Da y 1 (first d ose of st u d y dr u g) t hr o u g h Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) da ys after l ast d ose of st u d y dr u g if E T.
2 6) Seri o us a d verse e v e nts will be c a pt ure d fr o m Da y 1 (first d ose of st u d y dr u g) t hr o u g h Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) da ys after last d ose of st u d y dr u g if E T.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 2 of 9 9 
 
6.
Criteri a f or E v al u ati o n
6. 1 
S afet y E n d p oi nts
T he safet y a n d t olera bilit y of A K 0 0 2 will be assesse d b y deter mi ni n g t he f oll o wi n g: 
S y m pt o m- directe d p h ysical e xa mi nati o n
C ha n ges i n b o d y wei g ht a n d vital si g ns
He mat ol o g y
C ha n ges i n c o nc o mita nt me dicati o n use d ue t o A E
Bl o o d c he mistr y
Uri nal ysis
A nti- dr u g a nti b o dies
A d verse e ve nts
6. 2  
P h a r m ac o ki netic E n d p oi nts 
Bl o o d (ser u m) will be c ollecte d f or assess me nt of A K 0 0 2 c o nce ntrati o ns usi n g a vali d ate d 
e nz y me-li n ke d i m m u n os or be nt assa y ( E LI S A) met h o d. P h ar mac o ki n etic ( P K) bl o o d sa m ples 
will b e o btai ne d pre d ose o n E xte nsi o n Da y 1 (if n ot alrea d y c oll ecte d f or A K 0 0 2- 0 1 6 last st u d y 
visit), pre d ose o n E xte nsi o n Da y 1 9 7, a n d als o o n E xte nsi o n Da y 5 1 2 ( ± 3) or 3 5 ( ± 3) da ys after 
last d ose of st u d y dr u g, if E T, f or assess me nt of A K 0 0 2 c o nce ntr ati o ns. 
Bl o o d (ser u m) will be c ollecte d f or assess me nt of A D A usi n g a vali d ate d assa y m et h o d. T he 
A D A bl o o d sa m ples will be o btai ne d pre d ose o n E xte nsi o n Da y 1 (if n ot alrea d y c ollecte d f or 
A K 0 0 2- 0 1 6 last st u d y visit), pre d ose o n E xte nsi o n Da y 1 9 7, a n d als o o n E xte nsi o n Da y 5 1 2 
( ± 3 da ys) or 3 5 ( ± 3) d a ys after last d ose of st u d y dr u g, if E T, f or assess me nt of A D A. E xtra 
bl o o d (ser u m) sa m ples ma y als o be dra w n f or assess me nt of A D A, i n case of a n 
i m m u n o ge nicit y-s us pe cte d A E.  
6. 3 
Effic ac y E n d p oi nts
Dail y self-a d mi nistr ati o n of a disease-s pecific Patie nt Re p orte d O utc o me ( P R O) q uesti o n naire 
will b e use d t o e val uate si g ns a n d s y m pt o ms ass ociate d wit h E G a n d/ or E o D. T he P R O T otal 
S y m pt o m Sc ore ( T S S) will be use d t o e val uate efficac y a n d c o m prises 6 s y m pt o ms, as liste d 
bel o w:  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 3 of 9 9 
 
A b d o mi nal pai n i nte nsit y
Na usea i nte nsit y
F ull ness b ef ore meal i nte nsit y
L oss of a p petite i nte nsit y
Bl oati n g i nte nsit y
A b d o mi nal cra m pi n g i nte nsit y
C ha n ges i n q ualit y of life will be meas ure d b y t he S h ort- F or m Healt h a n d Well- Bei n g S ur ve y 
( S F- 3 6) q uesti o n naire. C ha n g es i n t he n u m ber of e osi n o p hils i n gastric a n d/ or d u o de nal m u c osa 
fr o m baseli ne will als o be e val uate d.  
6. 4  
P h a r m ac o d y n a mi c E n d p oi nts 
C ha n ge i n bl o o d e osi n o p hils will be assess e d at st u d y visits. 
7.
P atie nt Selecti o n
7. 1  
N u m ber of P atie nts 
U p t o a p pr o xi matel y 1 8 3 patie nts c o ul d be e nr olle d i n St u d y A K 0 0 2- 0 1 6 X, b ase d o n t he 
e nr oll me nt of St u d y A K 0 0 2- 0 1 6.  
7. 2  
St u d y P o p ul ati o n 
Patie nts w h o c o m plete St u d y A K 0 0 2- 0 1 6 or St u d y A K 0 0 2- 0 1 2 a n d meet t he i n cl usi o n criteria i n 
Secti o n 7. 3 a n d n o ne of t he e xcl usi o n criteria i n Secti o n 7. 4  will be eli gi ble f or e nr oll me nt.  
7. 3  
I ncl usi o n Criteri a 
Patie nts are eli gi ble f or t he st u d y if all of t he f oll o wi n g criteria are met: 
1)
Pr o vi de writte n i nf or me d c o nse nt.
2)
C o m plete d St u d y A K 0 0 2- 0 1 6, defi ne d as ha vi n g recei ve d 6 i nf usi o ns of st u d y dr u g a n d
f oll o we d t hr o u g h at least Da y 1 7 6 ( ± 3) or c o m plete d St u d y A K 0 0 2- 0 1 2, defi n e d as ha vi n g
recei v e d t he c o h ort-a p pr o priate n u m ber of d oses a n d f oll o we d f or 5 m o nt hs after last d ose
of st u d y dr u g.
3)
If p atie nt is o n pree xisti n g dietar y restricti o ns, willi n g ness t o mai ntai n t h ose restricti o ns,
u ntil t he se ve nt h d ose has bee n recei ve d. After t he se ve nt h d ose, diet ma y be li beralize d.
4)
A ble a n d willi n g t o c o m pl y wit h all st u d y pr o ce d ures.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 4 of 9 9 
 
5)
Fe male p atie nts m ust be eit her p ost me n o pa usal f or at least 1 year or s ur gicall y sterile (t u bal
li g ati o n, h ysterect o m y, or bilateral o o p h orect o m y) f or at least 3 m o nt hs, or if of
c hil d beari n g p ote ntial, ha ve a ne gati ve pr e g na nc y test a n d a gree t o use d ual met h o ds of
c o ntrace pti o n or a bstai n fr o m se x ual acti vit y u ntil t he e n d of t he st u d y or f or 1 2 0 da ys
f oll o wi n g t he last d ose of st u d y dr u g, w hic he ver is l o n ger.
6)
Male patie nts wit h fe male part ners of c hil d beari n g p ote ntial m ust a gree t o use a hi g hl y
effecti ve met h o d of c o ntrace pti o n ( vasect o m y is acce pta ble) u ntil t h e e n d of t he st u d y or f or
1 2 0 da ys f oll o wi n g t h e last d ose of st u d y dr u g, w hic he ver is l o n ger. All fertil e me n wit h
fe male part ners of c hil d beari n g p ote nti al s h o ul d be i nstr ucte d t o c o ntact t h e I n vesti g at or
i m m e diatel y if t he y s us pect t h eir part ner mi g ht be pre g na nt at a n y ti me d uri n g st u d y
partici pati o n.
7. 4  
E xcl usi o n Criteri a 
Patie nts will be e xcl u de d fr o m t h e st u d y if t he y meet a n y of t he f oll o wi n g criteria: 
1)
P o or t olera nce t o pre vi o us a d mi nistrati o n of A K 0 0 2 i n t he o pi ni o n of t he I n vesti g at or.
2)
K n o w n h y perse nsiti vit y t o a n y c o nstit ue nt of t he st u d y dr u g.
3)
A n y disease, c o n diti o n ( me dical or s ur gical), or car diac a b n or malit y, w hic h, i n t he o pi ni o n
of t he I n vesti gat or, w o ul d place t h e patie nt at i ncrease d ris k.
4)
Pl a n n e d or e x pecte d vacci nati o n wit h li ve atte n uate d vacci n es d uri n g t he treat m e nt peri o d,
or vacci n ati o n e x p ecte d wit hi n 5 half-li ves ( 4 m o nt hs) of A K 0 0 2 a d mi nistrati o n. All t y pes
a n d f or m ulati o ns of vacci nes (i ncl u di n g li ve atte n uate d v acci nes) a ut h orize d b y F D A or
ot her re g ulat or y a ut h orit y f or t he pre ve nti o n of C O VI D- 1 9 ma y be a d mi nistere d bef ore,
d uri n g, or after t his st u d y. T he vacci ne s h o ul d n ot be a d mi nistere d wit hi n 7 da ys pri or t o
a n d wit hi n 7 da ys after t he a d mi nistrati o n of A K 0 0 2 s o t hat a n y si de effects ca use d b y
eit her of t he 2 me dicati o ns ca n be m ore easil y deter mi ne d.
5)
W o me n w h o are pre g na nt, breastfee di n g, or pla n ni n g t o bec o me pre g n a nt w hil e
partici pati n g i n t h e st u d y.
6)
A n y ot her reas o n t hat, i n t he o pi ni o n of t he I n vesti gat or or Me dical M o nit or, ma kes t he
patie nt u ns uita ble f or e nr oll me nt.
8.
C o nc urre nt Me dic ati o ns
Pri or a n d c o nc o mita nt me dicati o ns i ncl u de b ot h prescri be d a n d o ver-t he-c o u nter me dicati o ns a n d
will b e rec or de d i n t he electr o nic Case Re p ort F or ms (e C R F). Me dicati o ns ta ke n f or E G/ E o D or
s y m pt o ms of E G/ E o D, as well as a n y m e dicati o ns ta ke n wit hi n 3 0 da ys pri or t o e xte nsi o n st u d y
Da y 1 s h o ul d be rec or d e d.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 5 of 9 9 
 
Me dicati o ns ta ke n pri or t o t he st u d y s h o ul d be mai ntai ne d, as m u c h as p ossi ble. P atie nts s h o ul d 
be a d vise d a gai nst ta ki n g a n y ne w me dicati o n or st o p pi n g a n e xisti n g me dicati o n, b ot h 
prescri be d a n d o ver-t he-c o u nter, wit h o ut c o ns ulti n g t he I n vesti gat or, u nless t he c ha n ge is 
re q uire d f or e mer ge nc y use. I m me diatel y pri or t o t he first i nf usi o n, t he st u d y site pers o n nel 
s h o ul d e ns ure t hat t he patie nt c o nti n ues t o meet t he i ncl usi o n criteria a n d n o ne of t h e e xcl usi o n 
criteria (i ncl u di n g use of pr o hi bit e d me dicati o ns as per A K 0 0 2- 0 1 6 criteria). 
All me dicati o ns use d d uri n g t he c o n d uct of t h e st u d y m ust be d oc u me nte d. 
8. 1  
P r o hi bite d Me dic ati o ns  
A n y bi ol o gics or ot her me dicati o ns t hat m a y i nterfere wit h t he st u d y, s uc h as i m m u n o-
s u p pressi ve or i m m u n o m o d ulat or y dr u gs (i. e., azat hi o pri n e, J A K i n hi bit ors, 6- merca pt o p uri ne, 
met h otre xate, c ycl os p ori n e, tacr oli m us, a nti- T N F, a nti-I L- 5, a nti-I L- 5 rece pt or, d u pil u ma b, 
a nti-I g E a nti b o dies, o maliz u ma b) are pr o hi bite d. T he use of s yste mic or t o pical c ortic oster oi ds 
wit h a d ose of > 1 0 m g/ da y of pre d nis o ne or e q ui vale nt is pr o hi bite d u nless it is d ue t o 
u nf oresee n circ u msta nces w he n it is d ee me d me dicall y necessar y t o treat a n u nrelate d me dical 
c o n diti o n or w he n gi v e n as a pre me di cati o n pri or t o i nf usi o n or t o tr eat a n I R R t hat occ urs d uri n g 
i nf usi o n.  
T here m a y be circ u msta nces w he n t h e use of s o me of t hese me dicati o ns d uri n g t h e st u d y ma y be 
acce pta ble. I n t hese cases, a p pr o val m ust be o btai ne d fr o m t he Alla k os Me dical M o nit or. A n 
E G D ma y n ot be perf or me d or ma y be dela ye d if a pr o hi bite d me dicati o n is starte d d uri n g t h e 
c o urse of t he st u d y, at t h e discreti o n of t h e Me dical M o nit or.  
8. 2  
All o we d Me dic ati o ns 
Me dicati o ns, ot her t ha n t h ose t hat are pr o hi bite d ( Secti o n 8. 1), s uc h as a nti hista mi nes, P PI, 
le u k otrie ne a nta g o nists, a n d s o di u m cr o m ol y n are all o we d d uri n g t he st u d y a n d, u nless re q uire d 
d ue t o u nf oresee n me dical necessit y, d oses are t o re mai n sta bl e.  
S yst e mic or s wall o we d c orti c oster oi ds wit h a d ose of 
1 0 m g/ d a y pre d nis o ne or e q ui v ale nt are 
acce pta ble, as l o n g as t he d ose re mai ns sta ble t hr o u g h o ut t h e st u d y. T he use of s yste mic or 
t o pical c ortic oster oi ds wit h a d ose of > 1 0 m g/ da y of pre d nis o ne or e q ui vale nt is per mitte d if it is 
dee me d t o be me dicall y necessar y t o treat a n u nrelate d me dical c o n diti o n or w he n gi ve n as a 
pre me dicati o n pri or t o i nf usi o n or t o tr eat a n I R R t hat occ urs d uri n g i nf usi o n.  
T here m a y be circ u msta nces w he n it is dee me d me dicall y necessar y t o alter ( or start/st o p) t he 
d ose of a n all o w e d me dicati o n. If t his me dicati o n is use d t o treat a n u nrelate d me dical c o n diti o n, 
it is n ot a de viati o n fr o m t he pr ot oc ol.  
All me dicati o n use will be d oc u me nte d i n t he e C R F. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 6 of 9 9 
 
9.
St u d y Tre at me nt
9. 1 
F or m ul ati o n of Test P r o d u ct
A K 0 0 2 is a h u ma nize d n o n-f uc os ylate d I g G 1 m o n ocl o nal a nti b o d y directe d a gai nst Si glec- 8. 
A K 0 0 2 dr u g pr o d uct is s u p plie d as a sterile li q ui d i n a si n gle- use 1 0 R glass vial wit h a fill 
v ol u me of n ot less t ha n 1 0 m L. T he pr o d uct is st ore d at 2° – 8° C.  
T he A K 0 0 2 f or m ulati o n is 
 
 p H 6. 0, i n sterile W FI.  
N ote : A K 0 0 2 will be referre d t o as “st u d y dr u g. ” T here is n o place b o i n t he e xte nsi o n st u d y. 
9. 2 
St u d y Dr u g P ac k a gi n g a n d L a beli n g
A K 0 0 2 dr u g pr o d uct is s u p plie d as a sterile li q ui d i n a si n gle- use 1 0 R glass vial wit h a mi ni m u m 
fill v ol u me of a p pr o xi matel y 1 0 m L. E ac h vial will be la bele d wit h t he re q uire d i n vesti gati o nal 
use state me nt, l ot n u m b er, S p o ns or na me, a n d directi o ns f or st ora ge. E ac h vial will als o c o ntai n a 
tear- off la bel wit h l ot a n d/ or kit n u m ber a n d s pace t o d oc u me nt t he patie nt i de ntificati o n ( PI D) 
n u m ber a n d pre parati o n date. T his tear- off la bel s h o ul d be a p plie d t o t he I n vesti gati o nal Pr o d uct 
D ose Calc ulati o n a n d Pre parati o n W or ks heet a n d mai ntai ne d wit h t he s o urce d oc u me nts. 
Glass vials are pl u g ge d wit h T efl o n-c oate d r u b ber st o p pers a n d seal e d wit h al u mi n u m seals. 
9. 3 
S u p pl y of St u d y Dr u g t o t he I n vesti g ati o n al Sit e
T he S p o ns or ( or desi g nee) will s hi p st u d y dr u g t o t he i n vesti gati o nal sit es. T h e i nitial st u d y dr u g 
s hi p me nt will be s hi p pe d after all re q uire d re g ulat or y d oc u me ntati o n a n d a p pr o vals ha ve bee n 
recei v e d b y t he S p o ns or, a n d t he c o ntract has bee n e xec ute d. S u bse q ue nt st u d y dr u g s hi p me nts 
will b e tri g gere d a ut o maticall y base d o n pre deter mi ne d s u p pl y le vels a n d e nr oll me nt acti vit y at 
t he site. 
9. 4 
St u d y Dr u g D os a ge a n d D ose Re gi m e n
All i nf usi o ns of A K 0 0 2 will be 3 m g/ k g. D osi n g will occ ur o n E xte nsi o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, 
1 4 1, 1 6 9, 1 9 7, 2 2 5, 2 5 3, 2 8 1, 3 0 9, 3 3 7, 3 6 5, 3 9 3, 4 2 1, 4 4 9, a n d 4 7 7 (
3 da ys). 
T he e xact a m o u nt of A K 0 0 2 t o be mi xe d wit h Na Cl will be calc ul ate d pri or t o eac h i nf usi o n a n d 
base d o n c urre nt patie nt b o d y wei g ht. St u d y dr u g will be a d mi nistere d as a si n gle peri p heral 
i ntra ve n o us i nf usi o n usi n g a n i nf usi o n p u m p as i n dicate d i n t h e st u d y P har mac y Ma n ual at t he 
st u d y visits s pecifie d i n T a ble 1 . 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 7 of 9 9 
 
9. 5 
P re p a r ati o n of St u d y Dr u g 
A st u d y p har macist or desi g nee will pre pare t he st u d y dr u g f or eac h i nf usi o n. Base d o n patie nt 
b o d y wei g ht o btai ne d t he da y of or t he da y pri or t o d osi n g, t he desi g nate d st u d y p har macist will 
pre pare t he a p pr o pri ate dil uti o n of A K 0 0 2 f or i ntra ve n o us a d mi nistrati o n.  
A p pr o priate ase ptic tec h ni q ue will be use d, a n d t he dr u g will be pre pare d acc or di n g t o t he 
p har mac y ma n ual f or A K 0 0 2. Refer t o t h e P h ar mac y Ma n ual f or a d diti o nal details a n d 
ste p- b y-ste p i nstr ucti o ns re gar di n g st u d y dr u g pre parati o n. 
T he i nf usi o n m ust be c o m plete d wit hi n 8 h o urs of pre parati o n. Pr e parati o n is w he n A K 0 0 2 is 
first mi xe d wit h Na Cl. 
9. 6  
St u d y Dr u g A d mi nistr ati o n 
S pecific i nstr ucti o ns o n a d mi nistrati o n a n d s u p plies re q uire d f or a d mi nistrati o n are detaile d i n 
t he P har mac y Ma n u al. I n ge neral, st u d y dr u g will be i nf use d t hr o u g h a peri p heral vei n 
i ntra ve n o us set. T he i ntr a ve n o us li n e s h o ul d be ke pt o pe n bef ore a n d after t he i nf usi o n wit h 
s ufficie nt q ua ntities of 0. 9 % Na Cl t o ass ure pate nc y.  
A v ol u me of 1 0 0 m L *  of t h e calc ulate d d ose of st u d y dr u g will be i nf use d o ver at least 4 h o urs 
o n E xte nsi o n Da y 1, o ver at least 2 h o urs o n E xte nsi o n Da ys 2 9 (
3), 5 7 ( 3), 8 5 ( 3), 1 1 3 ( 3), 
a n d 1 4 1 ( 3) a n d o ver at least 1 h o ur fr o m E xte nsi o n Da y 1 6 9 (
3) a n d o n war ds. If t h e i nf usi o n 
is sl o we d or i nterr u pte d, t he ti me ma y be e xte n de d l o n ger t ha n 4 h o urs, as l o n g as it d oes n ot 
e xcee d 8 h o urs.  
*
D ue t o t he r o u n di n g of t he t otal i nf usi o n v ol u me b y s o me pr o gra m ma ble i nf usi o n p u m ps,
a n i nf usi o n of 9 9 m L t o 1 0 1 m L will be c o nsi dere d a c o m plete i nf usi o n a n d will n ot be
rec or d e d as a de viati o n of t h e st u d y.
D ue t o pr o gra m mi n g li mitati o ns of s o me i nf usi o n p u m ps,  all v ol u mes ass o ciate d wit h t he
i nf usi o n ma y be r o u n de d t o t h e nearest 1/ 1 0t h m L.
F or t he first i nf usi o n of st u d y dr u g, patie nts will be pre me dicate d wit h 8 0 m g oral pre d nis o ne 
( or a p pr o ve d e q ui v ale nt) 1 2 – 2 4 h o urs pri or t o t h e start of t he st u d y dr u g i nf usi o n. F or s u bse q u e nt 
i nf usi o ns, pre me dicati o n ma y o nl y be use d at t he discreti o n of t he I n vesti gat or a n d wit h t h e 
writte n a p pr o val of t h e Me dical M o nit or. 
T he I V i nf usi o n ma y be i nterr u pte d a n d/ or t he rate ma y b e re d uce d if a patie nt has a n I R R. T he 
ti m e t h e i nf usi o n is i nitiate d/c o ncl u de d (i ncl u di n g a n y i nterr u pti o ns) will be d oc u me nte d i n t he 
e C R F. If t he i nf usi o n is restarte d after a n i nterr u pti o n, t h e i nf usi o n m ust b e c o m plete d wit hi n 
8 h o urs of pre parati o n. A d mi nistr ati o n will be disc o nti n ue d if, i n t he o pi ni o n of t he I n vesti gat or, 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 8 of 9 9 
 
a n i nterr u pte d i nf usi o n ca n n ot be restarte d f or safet y reas o ns or if t h e i nf usi o n ca n n ot be 
c o m plete d wit hi n 8 h o urs of pre parati o n. A d mi nistrati o n will als o be disc o nti n ue d i n a n y patie nt 
e x perie nci n g a seri o us a d verse e ve nt d uri n g t he c o urse of t he i nf usi o n. 
T he pati e nt will be o bser ve d at least 1 h o ur after t he e n d of eac h i nf usi o n, as p er I n vesti gat or 
discreti o n. 
9. 7 
St u d y Dr u g St or a ge 
A K 0 0 2 will be st ore d b y t h e st u d y sit es at 2º – 8º C i n a sec ure d, restricte d, a n d te m p erat ure-
m o nit ore d l o cati o n i n t he desi g nate d p har mac y, pe n di n g dr u g pre parati o n. T he 0. 9 % Na Cl will 
be st ore d at a m bie nt te m perat ure, per ma n ufact urer’s re q uir e me nts. St u d y dr u g will be st ore d i n 
a n area t h at is te m perat ure c o ntr olle d a n d m o nit ore d. If t he te m perat ure of st u d y dr u g st ora ge i n 
t he cli nic/ p har mac y e xcee ds or falls bel o w t his ra n ge, it will be re p orte d t o t h e S p o ns or usi n g t he 
g ui deli nes i n t h e P h ar m ac y Ma n ual. T he S p o ns or will n otif y t he site if t he st u d y dr u g is t o b e 
q uara nti ne d or ca n b e use d. 
9. 8  
Te m per at ure E xc ursi o ns 
A K 0 0 2 is sta ble at 2
– 8 C. I n case of te m perat ure e xc ursi o n d uri n g s hi p pi n g, or if t h e 
te m perat ure of dr u g st ora ge i n t he p har mac y e xcee ds or falls bel o w 2 – 8 C, please c o ntact 
Alla k os i m m e diatel y b y se n di n g t he c o m plete d Site T e m perat ure E xc ursi o n F or m t o 
cli ns u p pl y @ alla k os. c o m (e mail) or 1- 8 0 0- 7 8 3- 3 7 3 4 (fa x) bef ore a n y use of t he i n vesti gati o nal 
pr o d uct (I P). Attac h all a vail a ble i nf or mati o n wit h t h e Site T e m perat ure E xc ursi o n F or m 
i ncl u di n g te m perat ure l o gs s h o wi n g t h e e xte nt a n d d urati o n of t he e xc ursi o n.  
T he I P e x p ose d t o t he te m perat ure e xc ursi o n s h o ul d b e q uara nti ne d u ntil Alla k os deter mi nes 
w het h er t he I P is c o m pr o mise d or a p pr o ve d f or use. Alla k os or desi g nee will pr o vi de writte n 
i nstr ucti o ns re gar di n g use of t he I P, a n d t hese i nstr ucti o ns s h o ul d be a d de d t o t he p har mac y 
st u d y fil e. 
9. 9  
St u d y Dr u g Acc o u nt a bilit y 
T he site’s st u d y p har macist/ desi g nee is res p o nsi ble f or mai ntai ni n g acc urate a n d c urre nt rec or ds 
acc o u nti n g f or t he recei pt, dis pe nsi n g, pre parati o n, use, r et ur n ( or destr ucti o n), a n d fi nal 
dis p ositi o n of all i n vesti g ati o nal pr o d uct. All d osa ge calc ulati o ns will be d oc u me nte d o n t he 
s o urce d oc u me nts. T he Master I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g, or si milar f or m, 
s h o ul d be use d t o ca pt ure recei pt, dis pe nsi n g, a n d ret ur n ( or destr ucti o n). Electr o nic I P 
acc o u nta bilit y s yste ms ma y be use d de pe n di n g o n site prefere nce, as l o n g as t he sa me 
i nf or mati o n is ca pt ure d. T he st u d y m o nit or will verif y e ntries o n t hese d oc u me nts t hr o u g h o ut t h e 
c o urse of t he st u d y. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 3 9 of 9 9 
 
1 0.
P atie nt N u m beri n g, Str atific ati o n, R a n d o miz ati o n, a n d Bli n di n g
1 0. 1  
P atie nt N u m beri n g 
E ac h p atie nt w h o pr o vi des i nf or me d c o nse nt will be i d e ntifie d b y t he PI D assi g ne d i n 
St u d y A K 0 0 2- 0 1 6 or St u d y A K 0 0 2- 0 1 2. T he patie nt will mai ntai n t he sa me PI D t hr o u g h o ut t he 
st u d y.  
A pati e nt is c o nsi dere d e nr olle d i n t he A K 0 0 2- 0 1 6 X st u d y w he n t he s u bject recei ves t he first 
d ose of o pe n-la bel A K 0 0 2. 
1 0. 2
St r atific ati o n a n d R a n d o miz ati o n
T here will be n o ra n d o mizati o n or stratificati o n as all patie nts will recei v e A K 0 0 2.
1 0. 3
Bli n di n g
T here will be n o bli n di n g as all pati e nts will recei ve A K 0 0 2. 
1 1.
St u d y P r oce d ures a n d G ui deli nes
T a ble 1  pr o vi d es t h e sc he d ule of assess m e nts, de picti n g t he re q uire d testi n g pr oce d ures t o be
perf or me d f or t he d urati o n of t he st u d y.
W he n m ulti ple e val uati o ns are sc he d ule d at t he sa me ti me p oi nt, t h e pri orit y f or eac h will be as 
f oll o ws:  
S F- 3 6 (self-a d mi nistere d f or mat) s h o ul d be c o m plete d at t h e be gi n ni n g of t he st u d y visit
bef ore a n y ot her assess m e nts or pr oce d ures.
P R O q uesti o n naire s h o ul d be c o m plete d b y eac h st u d y s u bject dail y (at a p pr o xi matel y t he
sa me ti me eac h da y) d uri n g t h e tr eat m e nt a n d f oll o w- u p peri o ds.
P h ysi cal e xa mi n ati o ns (if nee de d) ca n be perf or me d, a n d uri ne sa m ples ca n be c ollecte d
eit her bef ore or after ot her e val uati o ns.
1 1. 1
Diet ar y a n d Lifest yle Restricti o ns
T he e xt e nsi o n st u d y d oes n ot i ncl u de fasti n g r e q uire me nts. Patie nts u n der we nt a sta n dar dize d 
baseli n e e val uati o n of eati n g h a bits, f o o d ha bits/restricti o ns, a n d f o o d a v oi da nce be ha vi ors 
d uri n g St u d y A K 0 0 2- 0 1 6 a n d St u d y A K 0 0 2- 0 1 2 a n d will be as k e d t o mai ntai n t he sa me diet 
t hr o u g h t h e first 6 m o nt hs of t he st u d y. After t he se ve nt h d ose has bee n recei ve d, diet a n d eati n g 
ha bits ma y be li berali ze d as desire d, wit h all c ha n ges n ote d i n t he C R F. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 0 of 9 9 
 
1 1. 2  
P h a r m ac o d y n a mi c/ Effic ac y- Rel ate d P r oce d ures 
1 1. 2. 1  
E G/ E o D P R O Q uesti o n n aire
A n electr o nic versi o n of t he P R O q uesti o n naire ( A p pe n di x 1 ) will b e c o m plete d dail y at 
a p pr o xi matel y t he sa me ti m e of da y, b y t he patie nt, t hr o u g h o ut t h e st u d y.  
Patie nts will n ot b e a ble t o c o m plete a q uesti o n naire m ore t ha n 2 4 h o urs after it is d ue a n d will 
o nl y be a ble t o g o bac k a n d m a ke c orrecti o ns or c ha n ges t o t h e data ori gi nall y e ntere d wit h t he 
a p pr o val of t he I n vesti g at or a n d E D C ve n d or. T he P R O i nf or m ati o n will be a ut o maticall y 
ca pt ure d a n d mai ntai n e d i n t he e P R O s yste m of t he E D C. 
A pa per versi o n of t he P R O q uesti o n naire is a vaila ble t o patie nts i n case t he y are n ot a ble t o 
c o m plete t he electr o nic versi o n f or a s h ort peri o d of ti me. O nl y 1 P R O s h o ul d be c o m plete d 
per da y, a n d t h e recall peri o d s h o ul d n ot be a n y m ore t ha n a p pr o xi m atel y 2 4 h o urs l o n g. 
T he i nf or mati o n will be ma n uall y ca pt ure d a n d e ntere d i nt o t he E D C b y t he st u d y site.  
If patie nts ha ve a hist or y of c o nc o mita nt at o pic der matitis or ast h ma, a n e xtr a q uesti o n will be 
p o p ulate d f or eac h rele va nt c o n diti o n o n t he P R O we bsit e f or t he patie nt t o c o m plete dail y. 
A pa per versi o n of t h ese q uesti o ns is a vaila ble if t he we bsite is n ot accessi ble or t he patie nt d oes 
n ot ha ve I nter net access ( A p pe n di x 5 ). A d diti o nall y, patie nts t hat recei v e d t h e d ys p ha gia 
q uesti o n i n t h e A K 0 0 2- 0 1 6 st u d y will c o nti n ue t o recei ve t he q uesti o n i n t he e xte nsi o n st u d y. 
1 1. 2. 2  
S h o rt F or m- 3 6 He alt h a n d W ell- Bei n g S ur ve y
A n electr o nic versi o n of t he S F- 3 6 Healt h a n d Well- Bei n g S ur v e y ( A p pe n di x 2 ) will b e 
c o m plete d b y t he p atie nt o n all d osi n g d a ys ( pre d ose), as w ell as o n e xte nsi o n Da ys ( 3) 5 1 2, 
5 3 3, a n d 5 6 1 or 3 5, 5 6, a n d 8 4 ( 3) da ys after last d ose of st u d y dr u g if E T. 
If t he q uesti o n naire was alrea d y c o m plete d wit hi n t h e last 2 8 da ys as p art of t he last st u d y visit i n 
t he A K 0 0 2- 0 1 6 st u d y, a d u plicate e ntr y is n ot re q uire d o n e xte nsi o n Da y 1. 
A pa per versi o n of t his q uesti o n naire will als o be a vaila ble f or c o m pleti o n i n case t h e electr o nic 
q uesti o n naire is n ot a vaila ble t o t he patie nt. T his i nf or mati o n will be e ntere d i nt o t he E D C b y t h e 
st u d y sit e.
1 1. 2. 3
C o m plete Bl o o d C o u nt wit h Differe nti al
Bl o o d will be o btai ne d f or C B C wit h differe nti al pr e d ose a n d 1 h o ur ( ± 1 5 mi n utes) p ost d ose o n 
all i nf usi o n da ys, as well as o n Da ys 5 1 2 ( ± 3), 5 3 3 ( ± 3), a n d 5 6 1 ( ± 3) or 3 5, 5 6, a n d 8 4 ( ± 3) da ys 
after last d ose of st u d y dr u g if E T. If alrea d y c ollecte d wit hi n t h e last 2 8 da ys as part of t he last 
st u d y visit i n t h e A K 0 0 2- 0 1 6 st u d y, a d u plicate pre d ose c ollecti o n o n e xte nsi o n Da y 1 is n ot 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 1 of 9 9 
 
re q uire d. F or patie nts e nteri n g t he st u d y fr o m A K 0 0 2- 0 1 6, all differe ntial cell c o u nts will re mai n 
bli n de d. 
T he bl o o d sa m ple will be pr ocesse d a n d s hi p pe d i n acc or da nce wit h t h e ce ntral la b orat or y 
ma n ual a n d la b orat or y kit i nstr ucti o ns. A ce ntr al la b orat or y will a nal yze t he bl o o d sa m ple a n d 
pr o vi de res ults f or C B C wit h differe nti al, i n cl u di n g he m o gl o bi n, he mat ocrit, platelet c o u nt, re d 
bl o o d cell c o u nt, w hite bl o o d cell c o u nt, a n d a bs ol ute differe nti al c o u nt ( ne utr o p hils, 
l y m p h oc ytes, m o n oc ytes, e osi n o p hils, a n d bas o p hils).  
1 1. 2. 4  
Es o p h a g o- G astr o- D u o de n osc o p y wit h Bi o ps y 
A n E G D wit h bi o ps y will b e perf or me d o n Da y 2 1 1 (
3) a n d Da y 5 0 5 ( 3) or 2 8 ( 3) da ys after 
last d ose of st u d y dr u g if E T. Bi o ps y sa m ples will be c ollecte d acc or di n g t o sta n dar dize d 
i nstr ucti o ns a n d will be se nt t o t he ce ntr al la b orat or y ( or desi g nee) f or fi xi n g a n d stai ni n g. A 
ce ntr al rea der will re p ort, a m o n g ot h er t hi n gs, ma xi m u m n u m ber of e osi n o p hils/ h pf a n d 
ma xi m u m n u m ber of tr y ptase- p ositi ve mast cells/ h pf, a n d gastric bi o psies will b e gra de d usi n g 
t he S y d ne y S yste m o n i nfla m mati o n, meta plasia, atr o p h y, a n d r eacti ve gastr o pat h y. T he Mars h 
Scale Classificati o n will b e use d t o gra de d u o de nal sa m ples. T he baseli n e E G D fr o m St u d y 
A K 0 0 2- 0 1 6 will be use d f or c o m paris o n.  
1 1. 2. 5  
B aseli ne Diet Assess me nt 
D uri n g t he A K 0 0 2- 0 1 2 a n d A K 0 0 2- 0 1 6 st u dies, t he I n vesti gat or or desi g nee as ke d patie nts a 
sta n dar dize d series of dietar y assess m e nt q uesti o ns. T he baseli ne diet s h o ul d be mai ntai ne d as 
m uc h as p ossi ble t hr o u g h t h e first 6 m o nt hs of t he e xte nsi o n st u d y e ve n if s y m pt o ms i m pr o ve. 
After t he se ve nt h i nf usi o n has bee n recei ve d, patie nts ma y li beralize t h eir diets a n d ma ke 
c ha n ges fr o m t he baseli ne diet, as desire d. C ha n ges fr o m t he baseli ne diet will be assesse d at 
e ver y st u d y visit a n d 3 5, 5 6, a n d 8 4 ( 3) da ys after l ast d ose if E T. 
1 1. 3  
S afet y- Rel ate d P r oce d u res 
1 1. 3. 1  
C o nc o mit a nt Me dic ati o ns 
All o n g oi n g c o nc o mita nt me dicati o ns a n d t hera pies will be tra nsferre d fr o m St u d y A K 0 0 2- 0 1 6 
i nt o St u d y A K 0 0 2- 0 1 6 X. A n y me dicati o ns use d f or pre me dicati o n d uri n g t he c o n d uct of t he 
E G D or f or treat me nt of I R R will be d oc u m e nte d i n t he A K 0 0 2- 0 1 6 X C o nc o mita nt Me dicati o ns 
L o g. D ose, r o ute, u nit, fre q u e nc y of a d mi nistr ati o n, i n dicati o n f or a d mi nistrati o n, a n d dates of 
me dicati o n will be ca pt ur e d. A n y me dicati o n recei ve d d uri n g t h e st u d y t hr o u g h E xte nsi o n 
Da y 5 6 1 (
3) or 8 4 ( 3) da ys after last d ose of st u d y dr u g, if E T, will be rec or de d. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 2 of 9 9 
 
1 1. 3. 2  
B o d y Wei g ht
B o d y wei g ht will be meas ure d pre d ose a n d use d t o deter mi ne t he a m o u nt of st u d y dr u g t o be 
mi x e d wit h Na Cl f or eac h i nf usi o n. B o d y wei g ht m ust be meas ure d o n t he da y of, or o n t he da y 
pri or t o, t he da y of eac h i nf usi o n. B o d y wei g ht will be e ntere d i nt o t he i nteracti ve res p o nse 
tec h n ol o g y (I R T) s yste m f or eac h d osi n g visit a n d will als o be rec or de d o n t he I n vesti gati o nal 
Pr o d uct D ose Calc ul ati o n a n d Pre parati o n W or ks heet t h at t h e p har macist or desi g nee will 
mai ntai n t o d oc u me nt eac h patie nt’s d ose cal c ulati o ns.  
B o d y wei g ht s h o ul d be c ollecte d o n sit e o n t h e da y of eac h st u d y dr u g i nf usi o n or o n t h e da y 
pri or t o eac h i nf usi o n. B o d y wei g ht will als o be ca pt ure d o n Da ys 5 1 2, 5 3 3, a n d 5 6 1 (
3) or 3 5, 
5 6, a n d 8 4 ( 3) da ys after last d ose of st u d y dr u g if E T.  
1 1. 3. 3  
S y m pt o m- Directe d P h ysic al E x a mi n ati o n 
A s y m pt o m- dir ecte d p h ysical e xa mi nati o n, a n e xa mi nati o n of re p orte d or o bser ve d patie nt 
s y m pt o ms warra nti n g e xa mi nati o n (i n t h e o pi ni o n of t h e I n vesti g at or) i n cl u di n g assess me nts of 
p ossi ble i nf usi o n sit e reacti o ns a n d I R R, will be perf or me d b y eit her t he I n vesti gat or or a 
q ualifie d desi g nee at all st u d y visits t hr o u g h E xte nsi o n Da y 5 6 1 or 8 4 (
3) da ys after l ast d ose of 
st u d y dr u g if E T. Ne w, a b n or mal, a n d cli nicall y si g nifi ca nt p h ysical e xa mi nati o n fi n di n gs m ust 
be d oc u m e nte d a n d will be f oll o we d b y t he st u d y d o ct or or S u bi n vesti gat or at t he ne xt sc he d ule d 
visit or s o o ner if cli nicall y i n dicate d or referre d t o a n o n-st u d y p h ysicia n.  
1 1. 3. 4  
Vit al Si g ns 
Vital si g ns, i ncl u di n g s yst olic a n d diast olic bl o o d press ure, p ulse, b o d y te m perat ure, a n d 
res pirat or y rate, will 
 mi n utes a n d bef ore a n y 
bl o o d dra w (e xce pt f or p ost-i nf usi o n f or w hic h vital si g ns will be o btai ne d as descri be d bel o w). 
O n d osi n g da ys, vital si g ns will be meas ure d wit hi n 3 0 mi n utes pre d ose, wit hi n 3 0 mi n utes after 
t he start of i nf usi o n, a n d wit hi n 3 0 mi n utes f oll o wi n g t he e n d of i nf usi o n. Refer t o t he sc he d ule 
of assess me nts i n T a ble 1 .  
I n vesti gat ors ma y ha ve a d diti o nal vital si g n pr o ce d ures perf or me d f or t he p ur p ose of treat me nt 
a d mi nistr ati o n or f oll o wi n g A E. 
1 1. 4  
Cli ni c al L a b or at or y Me as ure me nts  
Bl o o d a n d uri ne sa m ples f or cli nical safet y l a b orat or y tests will be c ollecte d at t he ti m e p oi nts 
prese nt e d i n T a bl e 1. I n vesti g at ors m a y ha ve a d diti o nal la b orat or y tests perf or me d f or t he 
p ur p ose of pla n ni n g treat me nt a d mi nistr ati o n or f oll o wi n g A E or a b n or mal la b orat or y val ues.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 3 of 9 9 
 
T he site will pr ocess a n d s hi p bl o o d a n d uri ne sa m ples per ce ntr al la b orat or y i nstr ucti o ns. A 
ce ntr al la b orat or y or desi g nee will a nal yze bl o o d a n d uri ne sa m ples a n d pr o vi de res ults f or t he 
cli nical safet y la b orat or y t ests.
Cli nical la b orat or y testi n g ma y be perf or me d l ocall y if t he site t hi n ks t h e ce ntr al la b orat or y ma y 
n ot be a ble t o pr o vi de res ults i n a ti m el y fas hi o n d ue t o staff re d ucti o ns, s hi p pi n g iss ues, or ot her 
fact ors ass ociate d wit h t he C O VI D- 1 9 pa n de mic. T he sit e will stri ve t o use t he ce ntral la b orat or y 
w he ne ver p ossi ble. 
F or a n y la b orat or y test val ue o utsi de t he refere nce ra n ge, t he I n vesti gat or will d eter mi ne cli nical 
si g nifica n ce ( N ot Cli nicall y Si g nifica nt [ N C S] or Cli nicall y Si g nifica nt [ C S]). A n a b n or mal la b 
val ue s h o ul d be d ee me d C S if a n y of t he f oll o wi n g c o n diti o ns are met:
T he a b n or malit y s u g gests a disease a n d/ or or ga n t o xicit y t hat is n e w or h as w orse ne d fr o m
baseli n e.
T he a b n or malit y is of a de gree t h at re q uires a d diti o nal acti ve ma na ge me nt, e. g., c ha n ge of
st u d y dr u g d ose, disc o nti n uati o n of t he st u d y dr u g, cl ose o bser vati o n, m ore fre q ue nt
f oll o w- u p assess me nts, or f urt her dia g n ostic i n vesti gati o n.
T heref ore, a cli nicall y si g nifica nt la b val ue is o ne t hat i n dicates a ne w disease pr ocess, a n 
e xacer bati o n or w orse ni n g of a n e xisti n g c o n diti o n, or re q uires f urt her acti o n t o be ta ke n.  
F or a n y la b orat or y test val ue o utsi de t he refere nce ra n ge t hat t he I n vesti gat or c o nsi ders cli nicall y 
si g nifica nt, t he I n vesti gat or will: 
Re peat t he test t o verif y t he o ut- of-ra n ge val ue.
F oll o w t h e o ut- of-ra n ge val ue t o a satisfact or y cli nical res ol uti o n.
Rec or d as a n A E a n y la b orat or y test val ue after start of st u d y dr u g t hat:
T he I n vesti gat or c o nsi ders cli nicall y si g nifica nt
Re q uires a patie nt t o be disc o nti n ue d fr o m t he st u d y or
Re q uires a patie nt t o recei v e tr eat m e nt
1 1. 4. 1  
C o m plete Bl o o d C o u nt wit h Differe nti al 
Bl o o d will be o btai ne d f or C B C wit h differe nti al as descri be d i n Secti o n 1 1. 2. 3 . If alrea d y 
c ollecte d wit hi n t he last 2 8 da ys as part of t h e last st u d y visit i n A K 0 0 2- 0 1 6, a d u plicate pre d ose 
c ollecti o n o n E xte nsi o n Da y 1 is n ot re q uire d f or A K 0 0 2- 0 1 6 X. T he p ost d ose c ollecti o n o n 
Da y 1 is still re q uir e d.  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 4 of 9 9 
 
1 1. 4. 2  
Bl o o d C he mistr y P r ofile 
Bl o o d f or c he mistr y tests will b e pr ocesse d a n d s hi p pe d i n acc or da nce wit h t h e ce ntral la b orat or y 
ma n ual a n d la b orat or y kit i nstr ucti o ns. 
If alrea d y c oll ecte d wit hi n t he last 2 8 da ys as part of t he last st u d y visit i n A K 0 0 2- 0 1 6, a 
d u plicate pre d ose c ollecti o n is n ot re q uir e d o n E xte nsi o n Da y 1. Bl o o d will be o btai n e d pre d ose 
o n all d osi n g da ys as well as o n Da ys 5 1 2, 5 3 3, a n d 5 6 1 or 3 5, 5 6, a n d 8 4 ( ± 3) da ys after last 
d ose of st u d y dr u g if E T. 
A ce ntral la b orat or y will a nal yze t he ser u m sa m ple a n d pr o vi de r es ults f or c he mistr y tests 
i ncl u di n g s o di u m, p otassi u m, c hl ori de, bicar b o nate, gl uc ose, bl o o d urea nitr o ge n, creati ni ne, 
creati ne ki n ase, calci u m, p h os p h or us, ma g nesi u m, t otal a n d direct bilir u bi n, t otal pr otei n, 
al b u mi n, as partate a mi n otra nsferase, ala ni ne a mi n otra nsferase, al kali ne p h os p hatase, ga m ma-
gl uta m yl tra nsferase, a n d lactate de h y dr o ge nase. 
1 1. 4. 3  
P re g n a nc y Test  
F or p atie nts of c hil d beari n g p ote ntial, t he site will perf or m a uri ne di psti c k pre g na nc y ( h C G) test 
pri or t o eac h i nf usi o n, as well as o n Da y 5 1 2 ( ± 3) or 3 5 ( ± 3 da ys) after last d ose of st u d y dr u g if 
E T. T h e site will perf or m t h e uri n e pre g na nc y test usi n g a n i n dicat or sti c k fr o m t he pre g na nc y 
test kit s u p plie d b y t he ce ntral la b orat or y a n d usi n g uri ne c oll ecte d f or t he uri nal ysis. T his test 
will b e assesse d pri or t o t h e start of eac h st u d y dr u g i nf usi o n. If alrea d y t este d wit hi n t he last 
2 8 da ys as part of t h e last st u d y visit i n A K 0 0 2- 0 1 6, a d u plicate test is n ot re q uire d o n E xte nsi o n 
Da y 1. If a patie nt has a p ositi ve pre g na nc y test, d osi n g will i m me di atel y be disc o nti n ue d.  
T o e ns ure patie nt safet y, eac h pre g na nc y i n a patie nt t hat recei v e d st u d y dr u g m ust b e re p orte d 
wit hi n 2 4 h o urs of lear ni n g of its occ urre nce. If t he patie nt recei v e d A K 0 0 2, t he pre g na nc y 
s h o ul d be f oll o we d t o deter mi n e o utc o me, i ncl u di n g s p o nta ne o us or v ol u ntar y ter mi nati o n, 
details of t he birt h, a n d t he prese nce or a bse nce of a n y birt h defects, c o n ge nit al a b n or malities, or 
mater nal a n d/ or ne w b or n c o m plicati o ns.  
W o me n w h o are s ur gicall y sterile (t u bal li gati o n, h ysterect o m y, or bilateral o o p h orect o m y) f or at 
least 3 m o nt hs or t h ose w h o are p ost me n o pa usal f or at least 1 year wit h F S H le vel > 3 0 mI U/ m L 
are n ot c o nsi d ere d t o be of c hil d beari n g p ote ntial. 
1 1. 4. 4  
Effecti ve Met h o ds of C o ntr ace pti o n f or All a k os St u dies
T his secti o n a p pli es t o st u d y s u bjects w h o are w o me n of c hil d beari n g p ote ntial ( W O C B P) a n d 
male st u d y s u bjects w h ose se x ual part ners are W O C B P.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 5 of 9 9 
 
A bsti ne nce is t he o nl y birt h c o ntr ol met h o d t h at is 1 0 0 % effecti ve i n pre ve nti n g pre g n a nc y. F or 
s u bjects w h o d o n ot practice a bsti ne nce, Alla k os rec o m me n ds t hat st u d y s u bjects use hi g hl y 
effecti ve met h o ds of c o ntrace pti o n, w hic h i ncl u de:
P er m a ne nt Steriliz ati o n:  T u bal li g ati o n, vasect o m y – 9 9 % eff ecti ve
L o n g- Acti n g R e versi ble C o ntr ace pti v es ( L A R C) :
I U D – 9 9 % effecti ve
I m pla nta ble r o d ( matc hstic k size d r o d t hat c o ntai ns pr o gesti n h or m o ne i m pla nte d u n der
t he s ki n of t h e u p per ar m; pre ve nts o v ulati o n) – 9 9 % effecti v e
C o ntr ace pti v e I nj ecti o n:
I ntra m usc ular or s u bc uta ne o us i njecti o n of pr o gesti n h or m o ne e ver y 3 m o nt hs –
9 6 % effecti v e
S h o rt- Acti n g H o r m o n al Met h o ds:
Oral c o ntrace pti v es or patc h – 9 1 % effecti v e
Va gi nal c o ntrace pti ve ri n g (releases 2 h or m o nes, pr o gesti n a n d estr o ge n, t o pre ve nt
o v ulati o n) – 9 1 % effecti v e
N ote:
Effecti ve ness rates o btai ne d fr o m t he Birt h C o ntr ol G ui de o n t h e F D A we b sit e 
(F D A, 2 0 2 1 ). 
Barrier a n d ot her met h o ds n ot liste d a b o ve w he n use d t o get h er as d ual met h o ds s uc h as a 
c o n d o m + dia p hra g m or c o n d o m + s per mici de are less effecti ve met h o ds, t h eref ore t h ese d ual 
met h o ds are n ot rec o m m e n de d as t he y c o ul d i ncrease t he ris k of bec o mi n g pre g na nt d uri n g t he 
st u d y or f oll o w- u p peri o d. W h e n usi n g d ual m et h o ds, at least 1 of t he met h o ds s h o ul d be a 
hi g hl y effecti v e met h o d of c o ntrace pti o n.
S u bjects, w h o e ntere d t he st u d y usi n g d ual met h o ds of c o ntrace pti o n t hat d o n ot i ncl u de at least 
1 of t he hi g hl y effecti ve met h o ds of c o ntrace pti o n, are all o we d t o c o nti n ue i n t he st u d y b ut m ust 
be i nf or me d of t he ris ks of n ot usi n g hi g hl y effecti ve met h o ds of c o ntrace pti o n.
1 1. 4. 5
Uri n al ysis
Uri ne sa m ples will be pr ocesse d a n d s hi p pe d i n acc or da nce wit h t h e ce ntral la b orat or y ma n u al
a n d la b orat or y kit i nstr ucti o ns. Uri ne will be o btai ne d o n E xte nsi o n Da ys 1, 1 9 7, a n d 5 1 2 or 
3 5 ( ± 3) da ys after last d ose of st u d y dr u g if E T. If alrea d y c ollecte d wit hi n t h e last 2 8 da ys as 
part of t he last st u d y visit f or A K 0 0 2- 0 1 6, a d u plicate c ollecti o n is n ot re q uir e d o n E xte nsi o n 
Da y 1. A ce ntral la b orat or y will a nal yze t h e uri ne sa m ple f or s pecific gra vit y, p H, pr otei n, 
gl uc ose, ket o nes, bl o o d, a n d le u k oc yte esterase. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 6 of 9 9 
 
1 1. 4. 6  
A nti- A K 0 0 2 A nti b o dies
Ser u m sa m ples f or A D A deter mi nati o n will be pr ocesse d a n d s hi p pe d fr oze n i n acc or da nce wit h 
t he ce ntral la b orat or y ma n ual a n d la b orat or y kit i nstr ucti o ns. Bl o o d will be c ollecte d f or 
deter mi nati o n of A D A pre d ose o n E xte nsi o n Da ys 1, 1 9 7, a n d 5 1 2 ( ± 3 da ys) or 3 5 ( ± 3) da ys 
after last d ose of st u d y dr u g if E T. If alrea d y c ollecte d wit hi n t h e last 2 8 da ys as part of t he last 
st u d y visit i n A K 0 0 2- 0 1 6, a d u plicate c ollecti o n is n ot re q uire d o n E xte nsi o n Da y 1. F or patie nts 
e nteri n g fr o m St u d y A K 0 0 2- 0 1 2, a baseli ne c oll ecti o n is re q uire d pri or t o t he first d ose of st u d y 
dr u g i n A K 0 0 2- 0 1 6 X. 
A ce ntral la b orat or y will a nal yze t he sa m ple f or A D A usi n g a vali date d assa y m et h o d. S p ecific 
i nf or mati o n o n A D A sa m ple c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt will be pr o vi de d i n t he 
ce ntr al la b orat or y ma n u al. Bl o o d sa m ples f or A D A will als o be c ollecte d a n yti me a n 
i m m u n o ge nicit y-relate d A E occ urs. 
1 1. 4. 7  
P h a r m ac o ki netics a n d St or a ge 
Bl o o d sa m ples f or ser u m P K assess m e nts will be pr o cesse d a n d s hi p pe d fr oze n i n acc or da nce 
wit h t h e ce ntr al la b orat or y m a n ual a n d la b orat or y kit i nstr ucti o ns. Bl o o d will be c ollecte d f or P K 
assess me nts pre d ose o n E xte nsi o n Da ys 1, 1 9 7, a n d 5 1 2 ( ± 3 da ys) or 3 5 ( ± 3) da ys after last d ose 
of st u d y dr u g if E T. If alrea d y c ollecte d wit hi n t h e last 2 8 da ys as part of t h e last st u d y visit i n 
A K 0 0 2- 0 1 6, a d u pli cate pre d ose c ollecti o n is n ot re q uire d o n E xte nsi o n Da y 1. F or patie nts 
e nteri n g fr o m St u d y A K 0 0 2- 0 1 2, a baseli ne c oll ecti o n is re q uire d pri or t o t he first d ose of st u d y 
dr u g i n A K 0 0 2- 0 1 6 X. 
A K 0 0 2 c o nce ntrati o ns will b e deter mi ne d b y t he ce ntr al la b orat or y or desi g nee usi n g a vali d ate d 
E LI S A met h o d.  S pecific i nf or mati o n o n P K sa m ple c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt 
will b e pr o vi d e d i n t he ce ntr al la b orat or y ma n ual.  
1 1. 4. 8  
Hist a mi ne a n d Tr y pt ase 
If a na p h yla xis is s us pecte d, a bl o o d sa m ple s h o ul d be o btai ne d f or plas ma hista mi ne a n d tr y ptase 
le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms. T he sa m ple s h o ul d be se nt t o t he ce ntr al 
la b orat or y f or pr ocessi n g.  
1 1. 4. 9  
I g E 
Bl o o d will be c ollecte d f or deter mi nati o n of ser u m I g E l e vels a n d se nt t o t he ce ntr al la b orat or y 
f or pr ocessi n g. Bl o o d will be c ollecte d pre d ose o n E xte nsi o n Da y 1 a n d D a y 5 1 2 ( ± 3) or 
3 5 ( ± 3) da ys after last d ose of st u d y dr u g if E T. If alrea d y c ollecte d wit hi n t h e last 2 8 da ys as 
part of t he last st u d y visit i n A K 0 0 2- 0 1 6, a d u plicate pre d ose c ollecti o n is n ot re q uire d o n 
E xte nsi o n Da y 1. F or patie nts e nteri n g fr o m St u d y A K 0 0 2- 0 1 2, a baseli ne c ollecti o n is re q uire d 
pri or t o t he first d ose of st u d y dr u g i n A K 0 0 2- 0 1 6 X. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 7 of 9 9 
 
1 1. 4. 1 0  C O VI D- 1 9 Testi n g 
T esti n g f or C O VI D- 1 9 is n ot re q uire d f or t his st u d y b ut ma y be i m ple me nte d b y t he st u d y site at 
a n y ti me d uri n g t h e st u d y d ue t o safet y re g ulati o ns or pr oce d ures. T esti n g f or C O VI D- 1 9 ma y be 
i n di vi d uall y ma n date d b y E G D facilities a n d, if t his is re q uire d, will be c o nse nte d t hr o u g h t he 
site a n d n ot liste d i n t h e A K 0 0 2- 0 1 6 X i nf or me d c o nse nt f or m (I C F). 
1 2.
E v al u ati o ns a n d P r oce d ures b y Visit
Writte n, i nf or me d c o nse nt will be o bt ai ne d bef ore a n y st u d y pr oce d ure is perf or me d.
Ge neral I nf or mati o n: 
E val uati o ns a n d pr oce d ures b y visit are s h o w n i n T a ble 1 .
All rec or de d cl oc k ti m es s h o ul d utilize a 2 4- h o ur cl oc k.
E xte nsi o n Da y 1 is t he da y of t he first i nf usi o n i n t his e xte nsi o n st u d y.
1 2. 1  
P ri or t o E xte nsi o n D a y 1  
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o E xte nsi o n Da y 1: 
O btai n writte n i nf or me d c o nse nt pri or  t o patie nt recei vi n g pre me dicati o n.
Verif y eli gi bilit y f or t he st u d y.
Patie nt t o self-a d mi nister 8 0 m g oral pre d nis o ne ( or a p pr o ve d alter n ati v e) 1 2 – 2 4 h o urs pri or
t o pre dicte d i nf usi o n start.
1 2. 2  
E xte nsi o n D a y 1 – First D a y of D osi n g 
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
C o nfir m c o nti n ui n g eli gi bilit y f or t h e st u d y.
Acti vate patie nt access t o Vie d o c M E w e bsit e a n d i nstr uct patie nt o n use of t he w e bsit e t o
c o m plete t he q uesti o n naire(s). Use t he e P R O T eac hi n g T o ol ( A p pe n di x 4) t o re mi n d
patie nts o n t he use of t he electr o nic platf or m.
Ha ve patie nt c o m plete S F- 3 6 Healt h S ur ve y. O btai n fr o m last st u d y visit of A K 0 0 2- 0 1 6 if
t he visit occ urre d wit hi n 2 8 da ys pri or t o E xte nsi o n Da y 1.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d b o d y wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges i n baseli n e diet. O btai n fr o m last st u d y visit of A K 0 0 2- 0 1 6 if t he
visit occ urre d wit hi n 2 8 da ys pri or t o E xte nsi o n Da y 1.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 8 of 9 9 
 
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he start of t he i nf usi o n.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d. O btai n fr o m last st u d y visit of
A K 0 0 2- 0 1 6 if t he visit occ urre d wit hi n 2 8 da ys pri or t o E xte nsi o n Da y 1.
C ollect bl o o d sa m ples f or C B C, bl o o d c he mistr y, I g E, A D A, a n d P K. O btai n fr o m last
st u d y visit of A K 0 0 2- 0 1 6 if t he visit occ urre d wit hi n 2 8 da ys pri or t o E xte nsi o n Da y 1.
Differe nti al cell c o u nts fr o m A K 0 0 2- 0 1 6 will re mai n bli n de d.
C ollect uri n e f or uri nal ysis. O btai n fr o m l ast st u d y visit of A K 0 0 2- 0 1 6 if t he visit occ urre d
wit hi n 2 8 da ys pri or t o E xte nsi o n Da y 1.
Perf or m uri ne pre g na nc y test. O btai n fr o m last st u d y visit of A K 0 0 2- 0 1 6 if t he visit
occ urre d wit hi n 2 8 da ys pri or t o E xte nsi o n Da y 1.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g  usi n g t h e b o d y wei g ht o btai n e d at
t he visit or t he da y pri or t o E xte nsi o n Da y 1. T he fi n al c o m bi ne d v ol u me of t he I V ba g of
st u d y dr u g + 0. 9 % N a Cl will be 1 2 0 m L .
N ote : 1 0 0 m L  of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d. 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de: 
I nf use 1 0 0 m L of st u d y dr u g o ver at l east 4 h o urs usi n g a n i nf usi o n p u m p. Refer t o t he
P har mac y Ma n u al f or i nf usi o n rates. Rec or d t h e start a n d st o p ti mes of t he i nf usi o n
i ncl u di n g a n y ti m es t h e i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n: 
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 4 9 of 9 9 
 
1 2. 3  
E xte nsi o n D a y 2 9 ( ± 3) – D ose 2 
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges i n baseli n e diet.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote nti al. C o n d uct a uri n e pr e g na nc y test.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g  usi n g t h e b o d y wei g ht o btai n e d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0  m L.
N ote : 1 0 0 m L  of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d. 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de:
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 2 h o urs o n E xte nsi o n
Da y 2 9. Refer t o t he P har mac y Ma n ual f or i nf usi o n rates. Rec or d t he start a n d st o p ti mes of
t he i nf usi o n i ncl u di n g a n y ti mes t he i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n: 
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 0 of 9 9 
 
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit.
1 2. 4  
E xte nsi o n D a y 5 7 ( ± 3) – D ose 3  
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote nti al. C o n d uct a uri n e pr e g na nc y test.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g  usi n g t h e b o d y wei g ht o btai n e d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0  m L.
N ote : 1 0 0 m L  of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d. 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de:
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 2 h o urs, de pe n di n g o n t he
I n vesti gat or’s discreti o n a n d t olera nce t o pri or i nf usi o ns. Refer t o t he P har mac y Ma n ual f or
i nf usi o n rates. Rec or d t h e start a n d st o p ti m es of t he i nf usi o n i ncl u di n g a n y ti mes t he
i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 1 of 9 9 
 
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n:
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit.
1 2. 5
E xte nsi o n D a y 8 5 ( ± 3) – D ose 4 
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote nti al a n d c o n d uct uri n e pre g na nc y test.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g  usi n g t h e b o d y wei g ht o btai n e d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0  m L.
N ote : 1 0 0 m L  of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d. 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de: 
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 2 h o urs, de pe n di n g o n t he
I n vesti gat or’s discreti o n a n d t olera nce t o pri or i nf usi o ns. Refer t o t he P har mac y Ma n ual f or
i nf usi o n rates. Rec or d t h e start a n d st o p ti m es of t he i nf usi o n i ncl u di n g a n y ti mes t he
i nf usi o n is i nterr u pte d.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 2 of 9 9 
 
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n:
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 
1 2. 6  
E xte nsi o n D a y 1 1 3 ( ± 3) – D ose 5 
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote nti al a n d perf or m uri n e pre g na nc y test.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g usi n g t h e b o d y wei g ht o btai ne d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0 m L.
N ote :
1 0 0 m L of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d.
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de:


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 3 of 9 9 
 
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 2 h o urs, de pe n di n g o n t he
I n vesti gat or’s discreti o n a n d t olera nce t o pri or i nf usi o ns. Refer t o t h e P har mac y Ma n ual f or
i nf usi o n rates. Rec or d t h e start a n d st o p ti m es of t he i nf usi o n i ncl u di n g a n y ti mes t he
i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d a d verse
e ve nt is s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma
hista mi ne a n d tr y ptase le vels wit hi n 1 – 2 h o urs of t he o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n:
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 
1 2. 7  
E xte nsi o n D a y 1 4 1 ( ± 3) – D ose 6  
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote nti al a n d perf or m uri n e pre g na nc y test.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g  usi n g t h e b o d y wei g ht o btai n e d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0  m L.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 4 of 9 9 
 
N ote :
1 0 0 m L of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d 
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d. 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de: 
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 2 h o urs, de pe n di n g o n t he
I n vesti gat or’s discreti o n a n d t olera nce t o pri or i nf usi o ns. Refer t o t he P har mac y Ma n ual f or
i nf usi o n rates. Rec or d t h e start a n d st o p ti m es of t he i nf usi o n i ncl u di n g a n y ti mes t he
i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n: 
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 
1 2. 8  
E xte nsi o n D a y 1 6 9 ( ± 3) – D ose 7 
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote nti al a n d perf or m uri n e pre g na nc y test.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 5 of 9 9 
 
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g usi n g t h e b o d y wei g ht o btai ne d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0 m L.
N ote :
1 0 0 m L of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d. 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de: 
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 1 h o ur, de pe n di n g o n t he
I n vesti gat or’s discreti o n a n d t olera nce t o pri or i nf usi o ns. Refer t o t he P har mac y Ma n ual f or
i nf usi o n rates. Rec or d t h e start a n d st o p ti m es of t he i nf usi o n i ncl u di n g a n y ti mes t he
i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n: 
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 
1 2. 9  
E xte nsi o n D a y 1 9 7 ( ± 3) – D ose 8 
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 6 of 9 9 
 
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges t o baseli n e diet. C h a n ges are all o we d after t he se ve nt h d ose has
occ urre d a n d will be d oc u me nte d i n t he C R F.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote nti al a n d perf or m uri n e pre g na nc y test.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C, c he mistr y, P K, a n d A D A.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g  usi n g t h e b o d y wei g ht o btai n e d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0 m L .
N ote : 1 0 0 m L  of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d. 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de: 
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 1 h o ur, de pe n di n g o n t he
I n vesti gat or’s discreti o n a n d t olera nce t o pri or i nf usi o ns. Refer t o t he P har mac y Ma n ual f or
i nf usi o n rates. Rec or d t h e start a n d st o p ti m es of t he i nf usi o n i ncl u di n g a n y ti mes t he
i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n: 
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 7 of 9 9 
 
1 2. 1 0  E xte nsi o n D a y 2 1 1 ( ± 3) – First E G D 
T he o n-treat m e nt E G D s h o ul d be c o m plete d 1 4 ( ± 3) da ys after t he ei g ht h d ose of st u d y dr u g. All 
ris ks a n d ass ociate d details re gar di n g t h e E G D pr oce d ure will b e disc usse d wit h t he patie nt b y 
t he E G D pr o vi der.  
T he f oll o wi n g pr oce d ures will be perf or me d:
Patie nt s h o ul d arri ve fasti n g f or t he E G D pr oce d ure as s pecifie d b y i nstr ucti o ns fr o m t he
E G D pr o vi der.
C ollect A E, S A E, a n d c ha n ges i n c o nc o mita nt me dicati o ns. Ca pt ure all c o nc o mita nt
me dicati o ns pr o vi de d t o t he patie nt d uri n g t he E G D.
Perf or m t h e E G D wit h bi o ps y f oll o wi n g pr oce d ures pr o vi de d b y Alla k os a n d all E G D
facilit y sta n dar d o perati n g pr oce d ures.
1 2. 1 1  E xte nsi o n D a y 2 2 5 t o D a y 4 7 7 ( ± 3) – D oses 9 t o 1 8 
E xte nsi o n D a ys 2 2 5, 2 5 3, 2 8 1, 3 0 9, 3 3 7, 3 6 5, 3 9 3, 4 2 1, 4 4 9, a n d 4 7 7  
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o st u d y dr u g i nf usi o n: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht (i n k g).
E nter PI D a n d wei g ht (i n k g) i nt o I R T.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of i nf usi o n.
C ollect uri n e o nl y if patie nt is of c hil d beari n g p ote ntial a n d perf or m uri ne pre g n a nc y test.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
T he st u d y p har macist will pre pare st u d y dr u g at 3 m g/ k g usi n g t h e b o d y wei g ht o btai ne d at
t he visit. T he fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be
1 2 0 m L .
N ote :
1 0 0 m L of t he calc ulate d v ol u me of st u d y dr u g/ Na Cl mi xt ure will be a d mi nistere d
t o t h e patie nt. T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he 
pre parati o n of t h e I V li n e or t o be left o ver i n t he i nf usi o n ba g/t u bi n g w he n t h e 
i nf usi o n is c o m plete d.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 8 of 9 9 
 
Pr o ce d ures ass ociate d wit h t he i nf usi o n of st u d y dr u g i ncl u de: 
Pre me di cati o n o nl y t o b e a d mi nist ere d wit h t he writte n a p pr o val of t he Me dical M o nit or.
I nf use 1 0 0 m L of st u d y dr u g usi n g a n i nf usi o n p u m p o ver at least 1 h o ur, de pe n di n g o n t he
I n vesti gat or’s discreti o n a n d t olera nce t o pri or i nf usi o ns. Refer t o t he P har mac y Ma n ual f or
i nf usi o n rates. Rec or d t h e start a n d st o p ti m es of t he i nf usi o n i ncl u di n g a n y ti mes t he
i nf usi o n is i nterr u pte d.
C ollect vit al si g ns wit hi n 3 0 mi n utes after t he start of i nf usi o n.
A n u nsc he d ule d A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y-relate d A E is
s us pecte d. If a na p h yla xis is s us pecte d, c ollect a sa m ple of bl o o d f or plas ma hista mi n e a n d
tr y ptase le vels wit hi n 1 – 2 h o urs of t h e o nset of s y m pt o ms.
T he f oll o wi n g pr oce d ures will be perf or me d after st u d y dr u g i nf usi o n:
C ollect vit al si g ns wit hi n 3 0 mi n utes of t he e n d of i nf usi o n.
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t he e n d of i nf usi o n.
O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit.
1 2. 1 2
E xte nsi o n D a y 5 0 5 ( ± 3) or 2 8 ( ± 3) D a ys after L ast D ose – F oll o w- u p E G D
T he f oll o w- u p E G D s h o ul d be c o m plete d 1 4 ( ± 3) da ys after t he last d ose of st u d y dr u g. All ris ks 
a n d ass o ciate d details re gar di n g t h e E G D pr oce d ure will be disc usse d wit h t he patie nt b y t he 
E G D pr o vi der. 
T he f oll o wi n g pr oce d ures will be perf or me d:
Patie nt s h o ul d arri ve fasti n g f or t he E G D pr oce d ure, as s pecifie d b y i nstr ucti o ns fr o m t he
E G D pr o vi der.
C ollect A E, S A E, a n d c ha n ges i n c o nc o mita nt me dicati o ns. Ca pt ure all c o nc o mita nt
me dicati o ns pr o vi de d t o t he patie nt d uri n g t he E G D.
Perf or m t h e E G D wit h bi o ps y f oll o wi n g pr oce d ures pr o vi de d b y Alla k os a n d t he E G D
facilit y.
F or E arl y Ter mi n ati o n: Perf or m E G D 2 8 ( ± 3) da ys after last d ose of st u d y dr u g or pri or t o t his, 
if necessar y, t o e ns ure c o m plia nce wit h t he visit. If patie nt disc o nti n ues t he st u d y m ore t ha n 
2 8 da ys after last d ose of st u d y dr u g, perf or m t h e E G D as s o o n as p ossi ble, as directe d b y t he 
Me dical M o nit or.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 5 9 of 9 9 
 
1 2. 1 3  E xte nsi o n D a y 5 1 2 ( ± 3) or 3 5 ( ± 3) D a ys after L ast D ose – F oll o w- u p Visit 1 
T he f oll o wi n g pr oce d ures will be perf or me d:
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns.
C ollect uri n e f or all patie nts a n d perf or m uri ne pre g na nc y test if patie nt is of c hil d beari n g
p ote ntial.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C, c he mistr y, I g E, P K, a n d A D A.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 
F or E arl y Ter mi n ati o n:  Perf or m Safet y F oll o w- u p Visit 1, 3 5 ( ± 3) da ys after last d ose of st u d y 
dr u g or pri or t o t his, if necessar y, t o e ns ure c o m plia nce wit h t he visit. If pati e nt disc o nti n ues t h e 
st u d y m ore t h a n 3 5 da ys after last d ose of st u d y dr u g, perf or m t he visit as s o o n as p ossi ble as 
directe d b y t he Me dical M o nit or. 
1 2. 1 4  E xte nsi o n D a y 5 3 3 ( ± 3) or 5 6 ( ± 3) D a ys after L ast D ose – F oll o w- u p Visit 2 
T he f oll o wi n g pr oce d ures will be perf or me d: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 
F or E arl y Ter mi n ati o n:  Perf or m Safet y F oll o w- u p Visit 2, 5 6 ( ± 3) da ys after last d ose of st u d y 
dr u g or pri or t o t his, if necessar y, t o e ns ure c o m plia nce wit h t he visit.  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 0 of 9 9 
 
1 2. 1 5  E xte nsi o n D a y 5 6 1 ( ± 3) or 8 4 ( ± 3) D a ys after L ast D ose – F oll o w- u p Visit 3 
T he f oll o wi n g pr oce d ures will be perf or me d: 
Ha ve patie nt c o m plete t h e S F- 3 6 Healt h S ur ve y.
Deter mi ne b o d y wei g ht.
D oc u m e nt a n y c ha n ges t o baseli n e diet.
C ollect vit al si g ns.
Perf or m s y m pt o m- dir ecte d p h ysical e xa mi nati o n, as nee d e d.
C ollect bl o o d sa m ples f or C B C a n d c he mistr y.
C o nc o mita nt me dicati o n use a n d A E (i n cl u di n g A E SI a n d S A E) will be d oc u me nte d t hr o u g h o ut 
t he cli nic visit. 
F or E arl y Ter mi n ati o n: Perf or m S afet y F oll o w- u p Visit 3, 8 4 ( ± 3) da ys after last d ose of st u d y 
dr u g or pri or t o t his, if necessar y, t o e ns ure c o m plia nce wit h t he visit.  
1 3.
A d verse E v e nt Re p orti n g a n d D oc u me nt ati o n
1 3. 1  
A d verse E ve nts 
I n acc or da nce wit h 2 1 C o de of Fe deral Re g ulati o n ( C F R) 3 1 2. 3 2( b) a n d I nter nati o nal 
C o nfere nce o n Har m o nisati o n (I C H) G ui da nce E 2 A, a n a d verse e ve nt is a n y u nt o war d me dical 
occ urre nce i n a cli nical i n vesti gati o n of a patie nt a d mi nistere d a p har mace uti cal pr o d uct a n d t hat 
d oes n ot necessaril y ha ve a ca usal relati o ns hi p wit h t he tr eat m e nt. A n A E is t heref ore a n y 
u nfa v ora bl e a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y fi n di n g), s y m pt o m, or 
disease te m p orall y ass ociate d wit h t he a d mi nistr ati o n of a n i n vesti gati o nal pr o d uct, w het her or 
n ot relate d t o t hat i n vesti g ati o nal pr o d uct. A n u ne x pecte d A E is o ne of a t y pe n ot i de ntifie d i n 
nat ure, se verit y, or fre q ue nc y i n t h e c urre nt I n vesti gat or’s Br oc h ure or of greater se verit y or 
fre q ue nc y t ha n e x pecte d base d o n t he i nf or mati o n i n t h e I n vesti g at or’s Br oc h ure.  
E xa m ples of a n A E i ncl u de: 
Si g nifica nt w orse ni n g or e xacer bati o n of u n derl yi n g me dical c o n diti o n.
Si g nifica nt a b n or mal fi n di n gs fr o m p h ysical e xa mi nati o ns, vital si g ns or la b orat or y tests.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 1 of 9 9 
 
T he f oll o wi n g e xa m ples are n ot c o nsi dere d A E: 
Me dical or s ur gical pr oce d ure, alt h o u g h t he c o n diti o n lea di n g t o t he pr oce d ure is us uall y
a n A E.
A ntici pate d da y-t o- da y fl uct uati o ns of pree xisti n g me dical c o n diti o ns (i ncl u di n g la b orat or y
val ues) as l o n g as w orse ni n g fr o m baseli n e d oes n ot o cc ur.
Si g ns or s y m pt o ms of t he dis or der bei n g st u die d u nless t he y bec o me m ore se vere or occ ur
wit h a greater fre q ue nc y t ha n occ urri n g at baseli n e.
N or mal pr o gressi o n of t h e dis or der bei n g st u die d u nless it is m ore se vere or o cc urs wit h
greater s pee d/fre q ue nc y t ha n e x pecte d.
All A E, w het her elicite d b y q uesti o ns fr o m st u d y staff, v ol u nteere d, or n ote d o n p h ysical 
e xa mi n ati o n/la b orat or y testi n g, a n d re gar dless of ca usalit y or se verit y, will be assesse d a n d 
rec or d e d i n t he e C R F be gi n ni n g after t he first a d mi nistr ati o n of st u d y dr u g a n d e n di n g o n 
E xte nsi o n Da y 5 6 1 or 8 4 ( ± 3) d a ys after last d ose of st u d y dr u g if E T. 
T he assess me nt of a n A E will be d o ne p urs ua nt t o defi niti o ns set f ort h b y I C H G o o d Cli nical 
Practice ( G C P) g ui deli nes a n d a p plica ble re g ulat or y re q uir e me nts.
1 3. 2
Seri o us A d verse E ve nts 
A S A E is defi ne d as a n A E t hat meets 1 of t he f oll o wi n g criteria: 
Deat h
A life-t hreate ni n g a d verse e ve nt t hat places t he patie nt at ris k of deat h at t h e ti me of t he
e ve nt. It d oes n ot refer t o a n e ve nt t h at h y p ot h eticall y mi g ht ca use deat h if it were m ore
se vere.
I n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n.
A persiste nt or si g nifica nt disa bilit y/i n ca pacit y.
A c o n ge nital a n o mal y/ birt h defect occ urri n g i n t h e offs pri n g of a st u d y patie nt.
Ot her i m p orta nt me dical e ve nts ma y als o b e c o nsi dere d a S A E w he n, b ase d o n a p pr o priate
me dical j u d g me nt, t he y je o par dize t h e patie nt or re q uir e i nter ve nti o n t o pre ve nt o ne of t he
o utc o mes liste d a b o ve.
T he date t hat a n A E meets 1 of t he crit eria liste d a b o ve is t h e date t hat it bec o m es a n S A E. 
C o n versel y, t he date t hat t he S A E n o l o n ger meets 1 of t he criteria liste d a b o ve is t he e n d d ate of 
t he S A E. A ne w A E wit h a n o utc o me of “rec o veri n g” ma y be create d t o a d dress t he o n g oi n g A E 
o nce it is n o l o n ger c o nsi dere d seri o us.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 2 of 9 9 
 
Seri o us a d verse e ve nts will b e assesse d a n d rec or de d after t he first a d mi nistrati o n of st u d y dr u g 
a n d e n di n g o n E xte nsi o n Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) da ys after last d ose of st u d y dr u g if E T.
1 3. 3  
A d verse E ve nts of S peci al I nterest  
A d verse e ve nts of s peci al i nterest f or t his st u d y i n cl u de: 
Mali g na ncies c o nfir me d b y hist o pat h ol o gical re p ort. Mast cells a n d e osi n o p hils are part of
t he n or mal i m m u ne res p o nse a n d b y decreasi n g t heir f u ncti o n, A K 0 0 2 c o ul d t he oreticall y
i ncrease t he ris k of mali g na nc y.
Parasitic i nfecti o ns c o nfir me d b y p ositi ve cli nical la b orat or y test. E osi n o p hils are es peciall y
acti v e i n pr otecti n g t he b o d y fr o m parasitic i nfecti o ns a n d decreasi n g t heir f u ncti o n c o ul d
t he oreticall y i ncrease t he ris k of parasiti c a n d o p p ort u nistic i nfecti o ns.
O p p ort u nisti c i nfecti o ns (i nfecti o ns k n o w n t o be m ore se vere or occ ur m ore fre q ue ntl y i n
i m m u n os u p presse d p o p ulati o ns) as c o nfir me d b y p ositi v e cli nical la b orat or y t est.
I nf usi o n-relate d reacti o ns a n d h y perse nsiti vit y reacti o ns, i ncl u di n g a na p h yla xis.
A d verse e ve nts of s peci al i nterest will be assesse d be gi n ni n g after t he first a d mi nistr ati o n of 
st u d y dr u g a n d e n di n g o n E xte nsi o n Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) da ys after last d ose of st u d y dr u g if 
E T. A n y ne w A E SI m ust be rec or d e d i n t he A d verse E ve nt e C R F a n d desi g nate d as a n “a d verse 
e ve nt of s peci al i nterest. ” If ne w i nf or mati o n relate d t o a n y pre vi o usl y re p orte d A E SI is 
i de ntifie d, t he a p pr o priate e C R F s h o ul d be u p date d. 
1 3. 4  
I nf usi o n- Rel ate d Re acti o ns 
All A E c o nsi dere d b y t he I n vesti gat or t o be rel ate d t o t he i nf usi o n of t he bi ol o gical s u bsta nce 
a n d occ urri n g wit hi n 2 4 h o urs of t h e start of t he st u d y dr u g i nf usi o n, s h o ul d be ca pt ure d as 1 A E, 
ter me d “I nf usi o n- Relate d Reacti o n” (I R R). 
C o m m o n s y m pt o ms of I R R i ncl u de: 
Fl us hi n g
Na usea
C hills
V o miti n g
Bac k or a b d o mi nal pai n
S w eati n g
C hest disc o mf ort or ti g ht ness
Fe ver
Dizzi ness
Urticaria
S h ort ness of breat h
Pr urit us
Hea d ac he
Br o nc h os pas m
H y p ote nsi o n or h y perte nsi o n


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 3 of 9 9 
 
All s y m pt o ms e x perie nce d b y a patie nt d uri n g a n I R R will be liste d i n t he e C R F u n der 1 I R R, 
u nless t he I n vesti gat or belie ves a s y m pt o m is n ot part of t he I R R, i n w hi c h case it will be 
rec or d e d se paratel y. T he start ti me of t he I R R will be ca pt ure d as t he start ti me of t he first 
s y m pt o m, a n d t he e n d ti me of t he I R R will be ca pt ure d as t he e n d ti me of t he last s y m pt o m. 
A n y me dicati o ns use d wit hi n 2 4 h o urs of a n i nf usi o n f or t he treat m e nt of a n I R R are n ot 
c o nsi dere d pr o hi bite d me dicati o ns n or de viati o ns fr o m t he pr ot oc ol. 
1 3. 5  
A n a p h yl a xis 
A s us pici o n of a na p h yla xis will be caref ull y m o nit ore d a n d treate d acc or di n g t o sta n dar d of car e. 
E mer ge nc y cras h cart e q ui p me nt a n d me dicati o ns, i ncl u di n g m ulti ple d oses of e pi ne p hri ne, 
vas o press ors, a n d br o nc h o dil at ors, will be a vaila ble at all ti mes d uri n g t he c o n d uct of t h e st u d y. 
T o defi ne a na p h ylactic reacti o ns i n a c o nsiste nt a n d o bjecti v e ma n ner, all e ve nts of s us pecte d 
a na p h yla xis will b e e val u ate d usi n g Sa m ps o n’s Criteria f or A na p h yla xis ( A p pe n di x 7 ). T he 
assess me nt of a n A E will be d o ne p urs ua nt t o defi niti o ns set f ort h b y I C H G o o d Cli nical Practi ce 
( G C P) g ui deli nes a n d a p plica ble re g ulat or y re q uire me nts.  
If a patie nt e x perie nces si g ns or s y m pt o ms of a na p h yla xis, t he patie nt ma y be treate d wit h 
sta n dar d of car e, s uc h as di p he n h y dra mi n e, aceta mi n o p he n, met h yl pre d nis ol o ne, e pi ne p hri ne, 
a n d ot her s u p p orti ve meas ures al o n g wit h cessati o n of t he i nf usi o n.
1 3. 6  
E v al u ati n g A d verse E ve nts a n d Seri o us A d verse E ve nts
1 3. 6. 1  
Est a blis hi n g Di a g n osis 
W he ne ver p ossi ble, dia g n oses s h o ul d be gi ve n w he n si g ns a n d s y m pt o ms are d ue t o a c o m m o n 
eti ol o g y (e. g., d ys uria, uri nar y nitrit es s h o ul d be re p orte d as a uri n ar y tract i nfecti o n). If t he 
dia g n osis is n ot k n o w n, i n di vi d ual si g ns a n d s y m pt o ms s h o ul d be assesse d a n d rec or de d i n t he 
A d verse E ve nt e C R F as se parate A E. T h e I n vesti gat or ( or q ualifie d S u bi n vesti gat or) m ust assi g n 
t he A E attri b utes liste d i n t he f oll o wi n g secti o ns (T a ble 2 , T a ble 3 , a n d T a ble 4 ) a n d is 
res p o nsi ble f or e ns uri n g t heir ca pt ure i n t h e s o urce d oc u me ntati o n. 
1 3. 6. 2  
Assess me nt of I nte nsit y 
T he I n vesti gat or will use cli nical j u d g me nt as well as t he g ui deli nes lai d o ut i n t h e Nati o nal 
Ca ncer I nstit ute C o m m o n T er mi n ol o g y Criteria f or A d verse E v e nts ( C T C A E), versi o n 5. 0 or 
m ost c urre nt versi o n, t o assess t h e i nte nsit y of eac h A E a n d S A E ( T a ble 2 a n d A p pe n di x 3 ). 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 4 of 9 9 
 
T a bl e 2  
A d verse E ve nt Se verit y f or A d v erse E ve nts 
G r a de *
Descri pti o n
1  
Mil d; as y m pt o matic or mil d s y m pt o ms; cli ni cal or dia g n ostic o bser vati o ns o nl y; i nter ve nti o n 
n ot i n dicat e d 
2  
M o derate; mi ni m al, l ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g a ge a p pr o priat e 
i nstr u me ntal acti viti es of dail y li vi n g 
3  
Se v ere or m e di call y si g nifica nt b ut n ot i m me diat el y life-t hreat e ni n g, h os pitaliz ati o n or 
pr ol o n gati o n of h os pit alizati o n i n dicat e d; disa bli n g; li miti n g self-care a cti vities of dail y li vi n g 
4  
Life-t hre ate ni n g c o nse q ue nces, ur ge nt i nter ve nti o n i n di cate d
5  
Deat h relate d t o a d verse e ve nt 
*
Gra de refers t o t he se verit y of t h e A E base d o n t he Nati o nal Ca ncer I nstit ut e C T C A E, versi o n 5. 0, a n d dis pl a ys
Gra des 1 t o 5 wit h u ni q ue cli nical descri pti o ns of se verit y f or eac h A E.
T he ter m “se vere” is a meas ure of i nte nsit y, a n d a se vere A E is n ot necessaril y a “seri o us” A E. 
W he n t he i nte nsit y of a n A E c ha n ges m ore t ha n o nce a da y, t h e ma xi m u m se verit y of t h e e ve nt 
s h o ul d be e ntere d i nt o t he A d verse E ve nt e C R F. If t he i nte nsit y c ha n ges o ver a n u m ber of da ys, 
t hese c ha n ges s h o ul d be rec or d e d se paratel y (i. e., as ha vi n g disti nct o nset dates). 
1 3. 6. 3  
Assess me nt of C a us alit y t o St u d y Dr u g 
T he I n vesti gat or s h o ul d use cli nical j u d g me nt as well as t he g ui d eli n es i n T a ble 3 t o assess t he 
relati o ns hi p bet wee n st u d y dr u g a n d A E. 
T a bl e 3  
A d verse E ve nt Rel ati o ns hi p t o St u d y D r u g 
Rel ati o ns hi p
t o St u d y Dr u g 
C o m me nt 
Relate d 
T here is clear e vi de nce t hat t he e ve nt is relate d t o t he use of st u d y dr u g (e. g., c o nfir mati o n b y 
p ositi ve rec halle n ge t est, if p ossi ble). A n ot her eti ol o g y is c o nsi d era bl y less li kel y. 
P ossi ble  
T he e ve nt ca n n ot be e x plai ne d b y t he pati e nt’s m e dical c o n diti o n, c o nc o mita nt t hera p y, or 
ot her ca uses, a n d t here is a pl a usi ble t e m p oral relati o ns hi p bet we e n t he e ve nt a n d st u d y dr u g 
a d mi nistrati o n.  
U nli kel y/ Re m ot e  
A n e ve nt f or w hi c h a n alter nati ve e x pla nati o n is m ore li kel y (e. g., c o nc o mita nt me di cati o ns 
or o n g oi n g m e di cal c o n diti o ns) or t he t e m p oral relati o ns hi p t o st u d y dr u g a d mi nistrati o n 
a n d/ or e x p os ure s u g g ests t hat a ca usal relati o ns hi p is u nli kel y. ( F or re p orti n g p ur p oses, 
U nli kel y/ Re m ot e will be gr o u pe d t o get her wit h N ot Rel ate d.)  
N ot Relate d  
T he e ve nt ca n be rea dil y e x plai ne d b y t he pati e nt’s u n derl yi n g me dic al c o n diti o n, 
c o nc o mit a nt t hera p y, or ot her ca uses, a n d t heref ore, t he I n vesti gat or belie ves n o rel ati o ns hi p 
e xists bet wee n t he e ve nt a n d st u d y dr u g.  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 5 of 9 9 
 
1 3. 6. 4  
Assess me nt of C a us alit y t o St u d y P r oce d u re 
T he I n vesti gat or s h o ul d use cli nical j u d g me nt as well as t he g ui d eli n es i n T a ble 4 t o assess t he 
relati o ns hi p bet wee n st u d y pr oce d ure a n d A E. Assess me nt of ca usalit y t o st u d y pr oce d ure s h o ul d 
i ncl u de ca usalit y t o s uc h ite ms as E G D wit h bi o ps y or bl o o d dra w (as a p pr o priate) or ot her.  
I nf usi o n-relate d reacti o ns s h o ul d n ot b e assesse d i n relati o n t o st u d y pr o ce d ure, o nl y i n relati o n 
t o st u d y dr u g.  
T a bl e 4  
A d verse E ve nt Rel ati o ns hi p t o St u d y P r oce d ure 
Rel ati o ns hi p t o
St u d y P r oce d ure 
C o m me nt 
Relate d 
T here is clear e vi de nce t hat t he e ve nt is rel ate d t o a st u d y pr oc e d ure. 
P ossi ble 
T h e e ve nt c a n n ot be e x plai ne d b y t he patie nt’s m e dical c o n diti o n, c o nc o mita nt t hera p y, or 
ot her ca uses, a n d t here is a pl a usi ble t e m p oral relati o ns hi p bet we e n t he e ve nt a n d a st u d y 
pr oce d ure.  
U nli kel y/ Re m ot e  
A n e ve nt f or w hi c h a n alter nati ve e x pla nati o n is m ore li kel y (e. g., c o nc o mita nt me di cati o ns 
or o n g oi n g m e di cal c o n diti o ns) or t he t e m p oral relati o ns hi p t o a n y st u d y pr oce d ure s u g gests 
t hat a c a usal relati o ns hi p is u nli kel y. ( F or re p orti n g p ur p oses, U nli k el y/ Re m ote will be 
gr o u pe d t o get her wit h N ot Rel at e d.) 
N ot Relate d  
T he e ve nt c a n be re a dil y e x plai ne d b y t he pati e nt’s u n derl yi n g me dical c o n diti o n, 
c o nc o mit a nt t hera p y, or ot her ca uses, a n d t heref ore, t he I n vesti gat or belie ves n o rel ati o ns hi p 
e xists bet wee n t he e ve nt a n d a st u d y pr oce d ure.  
1 3. 6. 5  
Acti o n T a ke n
Acti o n ta ke n wit h res pect t o st u d y dr u g will be cate g orize d as n o ne, st u d y dr u g per ma ne ntl y 
disc o nti n ue d (i nf usi o n is i nterr u pte d a n d is n ot restarte d, a n d n o s u bse q ue nt i nf usi o ns are gi v e n), 
st u d y dr u g t e m p oraril y wit h dra w n (i nf usi o n is i nterr u pte d a n d is restarte d, or t he ne xt i nf usi o n is 
still a d mi nistere d as pla n n e d), or ot her (s pecif y). 
Acti o n ta ke n wit h res pect t o st u d y partici pati o n will be cate g orize d as n o ne, wit h dra wal fr o m 
st u d y partici pati o n, or ot her (s pecif y).  
Acti o n ta ke n wit h res pect t o treat me nt of a n A E will be cate g orize d as n o ne, c o nc o mita nt 
me dicati o n, c o n c o mita nt pr oce d ure, or ot her (s pecif y).  
1 3. 6. 6  
Assess me nt of O utc o me 
E ve nt o utc o me at res ol uti o n or ti me of last f oll o w- u p will be rec or de d as: rec o vere d, rec o veri n g, 
n ot rec o vere d, rec o vere d wit h se q uelae, fatal, or u n k n o w n.  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 6 of 9 9 
 
1 3. 7  
A d verse E ve nt Re p orti n g P r oce d ures 
1 3. 7. 1  
All A d v erse E ve nts  
A n y cli nicall y si g nifica nt A E t hat is o n g oi n g at t h e ti me of st u d y c o m pleti o n or E T will be 
f oll o we d b y t he I n vesti gat or u ntil e ve nt res ol uti o n, t h e A E is ot her wise e x plai ne d, t he A E is n ot 
c o nsi dere d cli nicall y si g nifica nt b y t he I n vesti g at or, or t he patie nt is l ost t o f oll o w- u p. 
All n o n-seri o us A E i de ntifie d will be rec or d e d i n t he A d verse E ve nt e C R F be gi n ni n g fr o m t h e 
ti m e of first st u d y dr u g i nf usi o n a n d e n di n g o n E xte nsi o n Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) da ys after last 
d ose of st u d y dr u g if E T. All S A E i d e ntifie d will be rec or de d i n t h e A d verse E ve nt e C R F 
be gi n ni n g fr o m t h e ti m e of first st u d y dr u g i nf usi o n a n d e n di n g o n E xte nsi o n Da y 5 6 1 ( ± 3) or 
8 4 ( ± 3) da ys after last d ose of st u d y dr u g if E T. W he ne ver a p pr o priate, t h e C T C A E ( versi o n 5. 0 
or m ost c urr e nt v ersi o n) s h o ul d be use d f or na mi n g c o m m o n A E ( A p pe n di x 3 ). 
1 3. 7. 2  
Seri o us A d v erse E ve nt Re p orti n g 
I n t he e ve nt of a n y S A E re p orte d or o bser ve d d uri n g t he st u d y, w het her or n ot attri b uta ble t o t he 
st u d y dr u g, site pers o n nel m ust re p ort it i m m e diatel y ( wit hi n 2 4 h o urs of bec o mi n g a w are of 
t he S A E) b y tele p h o ne, fa x, or e mail t o t he S p o ns or, Alla k os I nc. 
T he S A E re p ort f or ms will be pr o vi d e d t o t he i n vesti gati o nal site t o assist i n c oll ecti n g, 
or ga nizi n g, a n d re p orti n g S A E, a n d t he f or ms m ust be c o m plete d wit h as m uc h i nf or mati o n as is 
a vaila ble a n d s h o ul d b e s u b mitte d t o t he S p o ns or wit hi n 2 4 h o urs of bec o mi n g a ware of t he 
e ve nt. Seri o us a d verse e ve nts m ust als o be rec or d e d o n t he A d v erse E ve nt e C R F a n d d esi g nate d 
as “seri o us. ”  
E ve n w he n o nl y mi ni mal i nf or mati o n is a vaila ble f or t he i nitial S A E re p ort, t he I n vesti g at or 
s h o ul d tr y t o ma ke a ca usalit y assess me nt, as t he ca usalit y is use d t o deter mi ne t he ti mi n g of 
re g ulat or y re p orti n g re q uire me nts. If t he I n vesti gat or or desi g nee is n ot a vaila ble t o si g n t he S A E 
re p ort o n i nitial s u b missi o n, t he y s h o ul d be c o ntacte d b y tele p h o ne a n d t heir assess m e nt 
d oc u me nte d o n t he S A E re p ort f or m ( wit h a n ote stati n g t hat si g nat ure is f ort h c o mi n g). T he 
I n vesti gat or m ay c h a n ge  t heir ca usalit y assess me nt base d o n f oll o w- u p i nf or m ati o n a n d s u b mit 
a n a me n de d S A E re p ort f or m.  
All eff orts will be m a de t o o btai n acc urate a n d c o m plete me di cal rec or ds f or t he S A E. All eff orts 
t o o btai n i nf or mati o n s h o ul d be d oc u me nte d i n t he patie nt s o urce d oc u me nts. 
T he site will n otif y t he I nstit uti o nal Re vi e w B o ar d (I R B) acc or di n g t o its g ui deli n es. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 7 of 9 9 
 
T he pati e nt’s c o n diti o n will be f oll o we d b y t he I n vesti gat or or desi g nee u ntil res ol uti o n of t he 
c o n diti o n or a ret ur n t o baseli n e le vels. If a d diti o nal visits are re q uire d, t he patie nt will be as ke d 
t o ret ur n t o t he st u d y site f or f urt her f oll o w-u p. If t he c o n diti o n is still o n g oi n g at t he ti me t he 
patie nt e xits t he st u d y, e ver y eff ort will be ma de t o c o nti n ue t o f oll o w u p wit h t h e patie nt f or a 
reas o na ble peri o d of ti me, as d eter mi ne d b y t he I n vesti gat or or u ntil t here is a ret ur n t o baseli ne 
or sta bili zati o n of t he c o n diti o n. As a d diti o nal i nf or mati o n bec o mes a vaila ble, s uc h as h os pital 
disc har ge n otes a n d pati e nt me dical r ec or ds, t he I n vesti g at or will be n otifie d a n d pr o vi de d wit h 
all rele va nt i nf or mati o n.  
All S A E t hat ha ve n ot res ol ve d b y t he e n d of t he st u d y or t h at ha ve n ot res ol ve d o n 
disc o nti n uati o n of t he patie nt’s partici pati o n i n t he st u d y m ust be f oll o we d u ntil a n y of t he 
f oll o wi n g occ urs:  
T he e ve nt res ol ves.
T he e ve nt sta bilizes.
T he e ve nt ret ur ns t o baseli ne if a baseli n e val ue is a vaila ble.
T he e ve nt ca n be attri b ute d t o a ge nts ot her t ha n t he i n vesti gati o nal pr o d uct or t o fact ors
u nrelate d t o st u d y c o n d uct.
It bec o mes u nli kel y t hat a n y a d diti o nal i nf or mati o n ca n be o btai ne d ( patie nt or healt h care
practiti o ner ref usal t o pr o vi de a d diti o nal i nf or mati o n, l ost t o f oll o w- u p after de m o nstrati o n
of d ue dili ge nce wit h f oll o w- u p eff orts).
Seri o us a d v erse e ve nts m ust be re p orte d wit hi n 2 4 h o urs t o:  
S A E Re p orti n g  
Fa x:  
+ 1- 8 8 8- 2 3 7- 7 4 7 5 
E mail: 
S A E @alla k os. c o m 
1 3. 7. 3  
P re g n a nc y Re p orti n g 
Pre g na ncies are ca pt ure d if t he y occ ur i n fe male patie nts or i n t h e se x ual part ners of m ale 
patie nts fr o m t h e ti me t he patie nt is first e x p ose d t o t he i n vesti gati o nal pr o d uct t hr o u g h 
E xte nsi o n Da y 5 6 1 ( ± 3) or 8 4 ( ± 3) d a ys after last d ose of st u d y dr u g if E T. 
Fe male patie nts m ust be i nstr ucte d t o disc o nti n ue all st u d y dr u gs a n d i nf or m t h e I n vesti gat or 
i m m e diatel y if t he y bec o me pre g na nt d uri n g t he st u d y. Male patie nts m ust be i nstr ucte d t o 
i nf or m t he I n vesti gat or i m me diatel y if t h eir part ner bec o mes pre g na nt d uri n g t he st u d y.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 8 of 9 9 
 
T he I n vesti gat or m ust r e p ort a n y pre g na nc y t o Alla k os wit hi n 2 4 h o urs of bec o mi n g a war e of it 
usi n g t h e pr o vi d e d pr e g na nc y re p orti n g f or ms. T he patie nt m ust b e i m me diatel y disc o nti n ue d 
fr o m st u d y dr u g. A n u nc o m plicate d pre g na nc y will n ot be c o nsi dere d a n A E or S A E, b ut all 
pre g na ncies i n patie nts w h o recei v e d A K 0 0 2 will be f oll o we d t hr o u g h ter m. F or m ale patie nts 
wit h fe male part ners w h o bec o me pre g n a nt, t h e site will as k t h e fat her (t he st u d y patie nt) t o 
pr o vi de i nf or m ati o n a b o ut t h e o utc o me of t he pre g na nc y a n d i nf or mati o n a b o ut t he b a b y. If 
detail e d healt h i nf or m ati o n a b o ut t he m ot her is re q uest e d b y Alla k os, a Pre g na nt Part ner 
I nf or mati o n Release F or m will be pr o vi d e d t o t he site f or t he m ot h er t o si g n.  
A n y c o n ge nital a b n or malities n ote d at birt h i n t he offs pri n g of a patie nt w h o recei ve d st u d y dr u g 
will b e re p orte d as a S A E. T he o utc o me of a n y pre g na nc y a n d t h e prese nce or a bse nce of a n y 
c o n ge nit al a b n or malit y will be rec or de d i n t he s o urce d oc u me ntati o n a n d re p ort e d t o t he Me dical 
M o nit or a n d S p o ns or.  
1 3. 7. 4  
A d verse E ve nt of S peci al I nt erest Re p orti n g 
Be gi n ni n g fr o m t he ti me of first st u d y dr u g i nf usi o n a n d e n di n g o n E xte nsi o n Da y 5 6 1 ( ± 3) or 
8 4 ( ± 3) da ys after last d ose of st u d y dr u g if E T, a n y ne w A E SI ( or ne w i nf or m ati o n r elate d t o a 
pre vi o usl y re p orte d A E SI) m ust b e rec or de d i n t he A d verse E ve nt e C R F a n d desi g nate d as a n 
“a d verse e ve nt of s pecial i nterest. ”  
A n A E SI t h at als o q ualifies as a S A E ( per Secti o n 1 3. 2 ) m ust als o be re p orte d as a S A E i n 
acc or da nce wit h Secti o n 1 3. 7. 2 . A d verse e ve nts of s pecial i nterest t hat are als o S A E m ust b e 
rec or d e d i n t he A d verse E ve nt e C R F a n d desi g nate d as b ot h “seri o us” a n d as a n “a d verse e ve nt 
of s pecial i nterest. ” T hese will b e re p orte d o n t he S p o ns or- pr o vi de d S A E f or ms a n d s h o ul d b e 
re p orte d t o t he S p o ns or wit hi n 2 4 h o urs of site a ware ness. 
1 3. 8  
Me dic al M o nit ori n g 
Dr. 
 or a p p oi nte d desi g nee s h o ul d be c o ntacte d directl y usi n g t he p h o ne n u m ber 
a n d/ or e mail a d dress bel o w t o re p ort me dical c o ncer ns or f or q uesti o ns re gar di n g safet y. 
All a k os Me dic al M o nit or 
, M D, P h D  
P h o ne: 
 
E mail: 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 6 9 of 9 9 
 
1 3. 9  
St u d y Wit h dr a w al Crit eri a
Patie nts will be disc o nti n ue d fr o m t h e st u d y i n t he e ve nt t hat:
Occ urre nce of a n e xcl usi o n crit eri o n, w hic h is cli nicall y rele va nt a n d affects t he patie nt’s
safet y, if disc o nti n uati o n is c o nsi dere d necessar y b y t he I n vesti gat or a n d/ or S p o ns or.
Ser u m tr a nsa mi n ases ( A L T a n d/ or A S T) > 3 × u p per li mit of n or mal ( U L N) a n d t otal
bilir u bi n > 2 × U L N (c o nfir me d b y s u bse q ue nt re peat) wit h o ut a n alter nati ve e x pla nati o n.
Ele vati o n of A L T a n d/ or A S T > 3 × U L N (c o nfir me d b y re peat) wit h t he a p peara nce or
w orse ni n g of s y m pt o ms t h o u g ht b y t h e I n vesti gat or t o be p ote ntiall y relate d t o he patic
i nfla m mati o n s uc h as fati g ue, na usea, v o miti n g, ri g ht u p per q ua dra nt p ai n or t e n der ness,
fe ver, a n d ras h.
1 3. 1 0
St u d y St o p pi n g R ules
T he st u d y ma y be disc o nti n ue d pre mat urel y i n t he e ve nt of a n y of t he f oll o wi n g:
A life-t hreate ni n g A E t hat is p ossi bl y or pr o ba bl y relate d t o treat m e nt.
A fatal A E t hat is p ossi bl y or pr o ba bl y relate d t o treat me nt.
Ne w i nf or mati o n lea di n g t o u nfa v ora ble ris k- be nefit j u d g me nt of t he st u d y dr u g.
S p o ns or’s decisi o n t h at c o nti n uati o n of t h e st u d y is u nj ustifia ble f or me dical or et hical
reas o ns.
Disc o nti n uati o n of de vel o p me nt of t he S p o ns or’s st u d y dr u g.
A p pr o val b y Healt h A ut h orities of t he S p o ns or’s st u d y dr u g.
Healt h A ut h orities a n d I R B will be i nf or m e d a b o ut t he disc o nti n uati o n of t he st u d y i n 
acc or da nce wit h a p pli ca ble re g ulati o ns. T h e st u d y ma y be ter mi n ate d or s us pe n de d o n re q uest of 
Healt h A ut h orities or S p o ns or.
1 4.
Disc o nti n u ati o n a n d R e pl a ce me nt of P atie nts
1 4. 1
D efi niti o n of St u d y C o m pleti o n
A pati e nt w h o c o m pletes visits t hr o u g h E xte nsi o n Da y 5 6 1 ( ± 3) will be rec or de d as ha vi n g 
c o m plete d t he st u d y.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 0 of 9 9 
 
1 4. 2  
E arl y Disc o nti n u ati o n of St u d y D r u g 
A pati e nt ma y be disc o nti n ue d fr o m st u d y treat me nt at a n y ti me if t he patie nt, t he I n vesti gat or, or 
t he S p o ns or f eels t hat it is n ot i n t he patie nt’s best i nterest t o c o nti n ue. T he f oll o wi n g is a list of 
p ossi ble reas o ns f or st u d y treat me nt disc o nti n uati o n: 
Patie nt wit h dra ws c o nse nt.
A n A E t hat i n t he o pi ni o n of t he I n vesti gat or res ults i n it bei n g i n t h e best i nterest of t he
patie nt t o disc o nti n ue st u d y treat m e nt.
Pr ot oc ol vi olati o n re q uiri n g disc o nti n uati o n of st u d y treat me nt.
Partici pati o n i n a n y ot her st u d y d uri n g t h e d urati o n of t his st u d y.
Use of a n o n- per mitt e d c o nc o mita nt dr u g wit h o ut pri or a p pr o val fr o m t h e Me dical M o nit or.
L oss of a bilit y t o freel y pr o vi d e c o nse nt t hr o u g h i m pris o n me nt or i n v ol u ntar y i n carcerati o n
f or treat me nt of eit her a ps y c hiatric or p h ysical (e. g., i nfecti o us disease) ill ness.
If a patie nt is wit h dra w n fr o m treat me nt d ue t o a n A E, t h e patie nt will be f oll o we d a n d treate d b y 
t he I n vesti gat or or desi g nee u ntil t he a b n or mal para meter or s y m pt o m h as res ol ve d or sta bilize d.  
All patie nts w h o disc o nti n ue st u d y dr u g treat me nt s h o ul d be e nc o ura ge d t o c o nti n ue o n st u d y 
a n d c o m plete assess me nts a n d pr o ce d ures acc or di n g t o T a ble 1 , if p ossi ble.  
Reas o na ble atte m pts will be ma de b y t he I n vesti gat or t o pr o vi de r eas o ns f or patie nt wit h dra wals. 
T he reas o n f or t he patie nt’s wit h dra wal fr o m t he st u d y or all atte m pts t o ac q uire s uc h, will be 
s pecifie d i n t he s o urce d oc u me nts.  
1 5.
St atistic al Met h o ds a n d Ge ner al C o nsi der ati o ns
T his secti o n o utli nes t he nat ure a n d rati o nale f or t he statistical met h o ds t o be use d f or a nal ysis of
t he data fr o m t he st u d y. A se parate St atistical A nal ysis Pl a n will descri be data ha n dli n g a n d
statisti cal tec h ni q ues i n f ull detail. T he Statisti cal A nal ysis Pl a n will c o ntai n a n y m o dificati o ns t o
t he a nal ysis pla n d escri be d bel o w.
All patie nt data will be liste d. W he n a p pr o priate, s u m mar y statistics of n u m ber of n o n- missi n g 
val ues, mea n, me dia n, sta n dar d de viati o n, mi ni m u m, a n d ma xi m u m will be c o m p ute d f or 
c o nti n u o us varia bles, a n d s u m mar y statistics of n u m ber a n d perce nta ge will be c o m p ute d f or 
cate g orical varia bles. N o f or mal statistical i nfere nces will be ma de. N o i m p utati o n will b e use d 
f or missi n g data.  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 1 of 9 9 
 
1 5. 1  
S a m ple Size 
U p t o a p pr o xi matel y 1 8 3 patie nts will be e nr olle d. 
1 5. 2  
D at a Sets A n al y ze d 
All patie nts w h o ha ve recei v e d st u d y me dicati o n will be i n cl u de d i n t h e Safet y p o p ulati o n f or 
safet y a nal ysis.  
1 5. 3  
De m o gr a p hic a n d B aseli n e C h ar acteristics 
T he f oll o wi n g d e m o gra p hic a n d baseli ne varia bles will be s u m marize d: 
De m o gra p hics
E xte nsi o n Da y 1 pre d ose vit al si g ns a n d la b orat or y tests
1 5. 4  P atie nt Dis p ositi o n 
T he n u m ber a n d perce nt of patie nts w h o c o m plete or disc o nti n ue fr o m t he st u d y will be 
s u m marize d. T h e reas o ns f or st u d y disc o nti n uati o n will be i ncl u de d i n t he s u m mar y. 
1 5. 5  
A n al ysis of S afet y E n d p oi nts  
A d verse E ve nts:  All A E will be c o d e d usi n g t he Me di cal Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A) a n d will be classifie d b y Me d D R A s yste m or ga n class a n d preferre d ter m. Listi n gs 
will i ncl u de all A E c ollecte d o n st u d y. T he s u m maries of A E will be base d o n T E A E, defi ne d as 
a n A E re p ort e d i n t he cli nical data base wit h a date of o nset ( or w orse ni n g) o n or after t he start 
date of t he first i ntra ve n o us i nf usi o n of t he st u d y me dicati o n.  
Patie nt i nci de nce ( N a n d %) of T E A E will be s u m marize d as f oll o ws: 
O ver vie w of T E A E t o i ncl u de
N u m ber ( %) of patie nts w h o re p ort at least o ne T E A E o verall, b y se verit y a n d
b y relati o ns hi p
N u m ber ( %) of patie nts w h o re p ort at least o ne seri o us T E A E
N u m ber ( %) of patie nts w h o re p ort at least o ne T E A E lea di n g t o treat me nt
disc o nti n uati o n
N u m ber ( %) of patie nts w h o re p ort at least o ne T E A E of s pecial i nterest
T E A E b y preferre d ter m
T E A E b y s yste m or ga n class a n d preferre d ter m


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 2 of 9 9 
 
T E A E b y ma xi m u m se verit y, s yste m or ga n class, a n d preferre d ter m
Dr u g-relate d T E A E b y s yste m or ga n class a n d preferre d ter m
T E A E lea di n g t o wit h dra wal b y s yste m or ga n class a n d preferre d ter m
Seri o us T E A E b y s yste m or ga n class a n d preferre d ter m
T E A E of s pecial i nterest b y s yste m or ga n class a n d preferre d ter m
Cli ni c al L a b or at or y Assess m e nts: Sa m ples will be o btai ne d f or t h e cli nical la b orat or y t ests 
i de ntifie d i n Secti o n 1 1. 4 , a n d la b orat or y tests t o be s u m marize d i n cl u de bl o o d c he mistr y, 
he mat ol o g y, uri nal ysis, a n d A D A.  
Descri pti ve statisti cs will be use d t o s u m marize la b orat or y res ults at baseli n e, eac h visit, a n d t he 
c ha n ge fr o m baseli ne f or eac h visit. I n a d diti o n, s hift ta bles will s u m m arize t h e la b orat or y r es ults 
relati ve t o n or mal refere nce ra n ges at baseli ne a n d eac h p ost- baseli ne ti me p oi nt.  
Vit al Si g ns:  Vital si g ns will be s u m m arize d at baseli ne, eac h visit, a n d c ha n ge fr o m baseli ne at 
eac h visit.  
P h ysic al E x a mi n ati o n:  Ne w or w orse ni n g s y m pt o ms i n t h e s y m pt o m- dir ecte d p h ysical 
e xa mi n ati o ns will be i ncl u de d i n t he b y- patie nt data listi n gs.  
C o nc o mit a nt Me dic ati o ns:  All me dicati o ns will be c o d e d usi n g t he m ost c urre nt W orl d Healt h 
Or ga nizati o n Dr u g Dicti o nar y. C o nc o mita nt me dicati o ns will be s u m marize d b y A nat o mical 
T hera pe utic C he mical Class a n d preferre d ter m.  
1 5. 6  
P h a r m ac o d y n a mi c/ Effic ac y- Rel ate d A n al yses 
T he wee kl y c ha n ge i n E G/ E o D P R O sc ores fr o m baseli ne T S S t o E xte nsi o n Da y 5 6 1 or 
8 4 ( ± 3) da ys after last d ose of st u d y dr u g will be calc ulate d. T he c ha n ge fr o m baseli ne t o 
E xte nsi o n Da y 5 6 1 or 8 4 ( ± 3) d a ys after last d ose of st u d y dr u g if E T. T he S F- 3 6 t otal a n d 
d o mai n sc ores will be s u m marize d descri pti vel y. C ha n ge a n d p erce nt c ha n ge fr o m baseli ne t o 
eac h sc he d ule d st u d y visit i n bl o o d e osi n o p hil c o u nt will be s u m marize d descri pti vel y.  
1 5. 7  
P atie nt C o nfi de nti alit y 
Patie nt i de ntit y s h o ul d be c o nfir me d b y t he prese ntati o n of a p h ot o i de ntificati o n t o e ns ure t h e 
c orrect i n di vi d ual is c o nse nte d, scree ne d, a n d e nr olle d (if eli gi ble).  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 3 of 9 9 
 
O nl y t he PI D, patie nt i nitials, a n d de m o gra p hics will be rec or de d i n t he e C R F. If t he patie nt’s
na me a p pears o n a n y s o urce d oc u me nt c ollecte d (e. g., h os pit al disc har ge s u m mar y), it m ust be 
re m o ve d fr o m t he d oc u m e nt if t h e d oc u me nt will be vie we d b y t he S p o ns or or a S p o ns or-
c o ntracte d st u d y ve n d or n ot per mitte d access t o patie nt i de ntif yi n g i nf or mati o n. All st u d y 
fi n di n gs will be st ore d i n electr o nic data bases. T h e patie nts will gi ve e x plicit writte n per missi o n 
f or re prese ntati ves of t he S p o ns or, re g ulat or y a ut h orities, a n d t he I R B t o i ns pect t heir me dical 
rec or ds t o verif y t he i nf or mati o n c oll ecte d. Patie nts will be i nf or m e d t h at all p ers o nal 
i nf or mati o n ma de a vaila ble f or i ns p ecti o n will be ke pt c o nfi d e nti al t o t he e xte nt per mitte d b y all 
a p plica ble state, l ocal, a n d f e deral data pr otecti o n/ pri vac y la ws a n d/ or re g ulati o ns a n d will n ot be 
ma de p u blicl y a vaila ble. If t he res ults of t h e st u d y are p u blis he d, t he patie nt’s i d e ntit y will 
re mai n c o nfi de ntial. 
At st u d y c hec k-i n t o t he st u d y sit e, patie nts will be a d vise d n ot t o s h are t heir st u d y i nf or mati o n 
wit h ot h er patie nts.  
1 6.
D at a C ollecti o n, Rete nti o n, a n d M o nit ori n g
1 6. 1  
D at a C ollecti o n I nstr u m e nts 
All staff at partici pati n g cli nical sit es will a d here t o g o o d d oc u me ntati o n practices. D ata will be 
e ntere d i nt o e C R Fs usi n g s o urce d oc u me nt data. S o urce d oc u me nts ma y i ncl u de b ut are n ot 
li mite d t o la b orat or y data, rec or de d data fr o m a ut o mate d i nstr u me nts, me dical pr o gress n otes, 
a n d e mail c orres p o n de nce.  
1 6. 2  
D at a M a n a ge me nt P r oce d ures 
T he data will be e ntere d i nt o a vali date d data base. T h e data ma na ge me nt gr o u p will b e 
res p o nsi ble f or data pr ocessi n g i n acc or da nce wit h pr oce d ural d oc u me ntati o n. Data base l oc k will 
occ ur o nce q ualit y ass ura nce pr oce d ures ha ve bee n c o m plete d. 
All pr oce d ures f or t he ha n dli n g a n d a nal ysis of data will be c o n d ucte d usi n g g o o d c o m p uti n g 
practices m eeti n g F D A g ui deli nes f or t he ha n dli n g a n d a nal ysis of data f or cli nical trials.  
1 6. 3  
D at a Q u alit y C o ntr ol a n d Re p orti n g 
After data ha ve bee n e ntere d i nt o t he st u d y data base, a s yste m of c o m p uterize d data vali dati o n 
c hec ks will be i m ple me nte d a n d a p pli e d t o t he data base o n a re g ular basis. Q ueries are e ntere d, 
trac ke d, a n d res ol ve d t hr o u g h t he electr o nic data ca pt ure s yste m directl y. T he st u d y data base will 
be u p date d i n acc or da nce wit h t he res ol ve d q ueries. All c ha n ges t o t he st u d y data base will be 
d oc u me nte d.  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 4 of 9 9 
 
1 6. 4  
D at a b ase L oc k
T he data base will be l oc ke d i n or der t o pr otect write access after t he f oll o wi n g prec o n diti o ns are 
f ulfille d: 
All rec or ds are e ntere d i n t he data base, a n d all data q ueries are res ol ve d.
All a d verse e ve nts are c o de d t o t he satisfacti o n of t he C hief Me di cal Officer.
All me dicati o ns are c o de d t o t he satisfacti o n of t he C hief Me dical Officer.
All decisi o ns are m a de re gar di n g all pr ot oc ol vi olati o ns.
Writte n a ut h orizati o ns t o l oc k t he data base are o btai ne d fr o m Alla k os Cli nical Data
Ma na ge me nt a n d t h e C hief Me dical Officer.
1 6. 5  
Arc hi vi n g of D at a
T he data base is safe g uar de d a gai nst u na ut h orize d access b y esta blis h e d sec urit y pr oce d ures; 
a p pr o priate b ac k u p c o pies of t he data base a n d relate d s oft ware files will be mai ntai ne d. 
Data bases are bac ke d u p b y t h e data base a d mi nistrat or i n c o nj u ncti o n wit h a n y u p dates or 
c ha n ges t o t h e data base.  
At critical j u nct ures of t he pr ot o c ol ( e. g., pr o d ucti o n of i nteri m re p orts a n d fi nal re p orts), data f or 
a nal ysis is l oc ke d a n d clea ne d per esta blis he d pr oce d ures.  
1 6. 6  
A v ail a bilit y a n d Rete nti o n of I n v esti g ati o n al R ec or ds
I n acc or da nce wit h 2 1 C F R 3 1 2. 6 2(c), G C P, a n d all ot her a p plica ble re g ulat or y re q uire me nts, 
f oll o wi n g c o m pleti o n or ter mi nati o n of t h e st u d y, t he S p o ns or or its desi g nee will retai n a c o p y 
of all st u d y rec or ds i n a li mite d-access st ora ge r o o m f or a mi ni m u m of 2 y ears after n otificati o n 
t hat t he i n vesti gati o ns h a ve bee n disc o nti n ue d a n d t he F D A has bee n n otifie d, or f or 2 years after 
all mar keti n g a p plicati o ns ha ve bee n a p pr o ve d. T he trial m aster file will be create d d uri n g t h e 
i m ple me ntati o n p hase of a st u d y, mai ntai ne d o n a n o n g oi n g basis t hr o u g h o ut t h e d urati o n of t he 
pr oject, a n d c oll ate d at t he e n d of t he st u d y. T he files will c o ntai n f ol ders t hat ma y i ncl u de b ut 
are n ot li mite d t o t he f oll o wi n g s u bcate g ories:
Fi n a ncial a gree m e nts
Re g ulat or y d oc u me nts
I R B D oc u me nts
Dr u g Acc o u nta bilit y
C orres p o n de nce


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 5 of 9 9 
 
Me dical Re p orts
Patie nt Data
M o nit ori n g Visit Re p orts
Sa m ple case re p ort f or ms a n d Case Re p ort F or m G ui deli nes
1 6. 7  
M o nit ori n g 
M o nit ori n g visits will be c o n d ucte d b y re prese ntati ves of t he S p o ns or acc or di n g t o 2 1 C F R 
Parts 5 0, 5 6, a n d 3 1 2 a n d I C H G C P G ui deli ne E 6. B y si g ni n g t his pr ot oc ol, t he I n vesti g at or 
gra nts per missi o n t o t he S p o ns or ( or desi g nee), a n d a p pr o priate re g ulat or y a ut h oriti es t o c o n d uct 
o n-site a n d/ or re m ote m o nit ori n g a n d/ or a u diti n g of all a p pr o priate st u d y d oc u me nt ati o n.
As necessit ate d b y t he C O VI D- 1 9 pa n de mic, m o nit ori n g of all a p pr o priate st u d y d oc u me ntati o n 
ma y occ ur off-site wit h re m ote access t o st u d y d oc u me nts as per mitt e d b y i n di vi d ual st u d y sit e 
re q uire me nts. 
1 7.
A d mi nistr ati ve, Et hic al, a n d Re g ul at or y C o nsi der ati o ns
T he st u d y will b e c o n d ucte d i n a ma n ner c o nsiste nt wit h t he Decl arati o n of Helsi n ki, Pr otecti o n
of H u ma n V ol u nteers ( 2 1 C F R 5 0), I R B ( 2 1 C F R 5 6 a n d I C H E 6), a n d O bli gati o ns of Cli nical
I n vesti gat ors ( 2 1 C F R 3 1 2 a n d I C H E 6). T he I n vesti gat or m ust als o c o m pl y wit h all a p plica ble
pri vac y re g ulati o ns (e. g., t he Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act [ HI P A A],
E ur o pea n U ni o n Data Pr otecti o n Directi v e 9 5/ 4 6/ E C).
1 7. 1
P r ot oc ol A me n d m e nts 
A n a me n d m e nt m ust be a gree d t o i n writi n g b y Alla k os I nc. a n d s u b mitt e d t o t he healt h a ut h orit y 
as a Cli nical Tri al A p plicati o n/I n vesti gati o nal N e w Dr u g a me n d me nt. Pr ot oc ol a me n d me nts 
ca n n ot be i m ple me nte d wit h o ut pri or writte n I R B a p pr o val e xce pt as necessar y t o eli mi nate 
i m m e diate safet y hazar ds t o patie nts. Writt e n a p pr o val of a pr ot o c ol a me n d me nt is n ot re q uire d 
pri or t o i m ple me ntati o n of c ha n ges t o t he pr ot oc ol t hat eli mi n ate i m me diate hazar d t o t h e patie nt; 
h o we ver, a p pr o val m ust be o btai ne d as s o o n as p ossi ble t hereafter. E ac h pr ot oc ol a me n d me nt 
m ust als o be si g ne d b y t he I n vesti gat or. 
1 7. 2
I nstit uti o n al Re vie w B o ar d 
T he pr ot oc ol a n d I C F will b e re vi e we d a n d a p pr o ve d b y t h e I R B of eac h p artici pati n g ce nter 
pri or t o st u d y i nitiati o n. All S A E, r e gar dless of ca usalit y, will be re p orte d t o t he I R B i n 
acc or da nce wit h t he st a n dar d o perati n g pr oce d ures a n d p olicies of t he I R B, a n d t he I n vesti gat or 
will k ee p t h e I R B i nf or me d as t o t he pr o gress of t he st u d y. T he I n vesti g at or will o btai n ass ura nce 
of I R B c o m plia nce wit h re g ulati o ns. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 6 of 9 9 
 
A n y d oc u me nts t hat t he I R B ma y nee d t o f ulfill its res p o nsi bilities (s uc h as pr ot o c ol, pr ot oc ol 
a me n d me nts, I n vesti gat or’s Br oc h ure, I C F, i nf or mati o n c o ncer ni n g patie nt recr uit me nt, pa y m e nt 
or c o m pe nsati o n pr oce d ures, or ot her perti ne nt i nf or mati o n) will be s u b mitte d t o t he I R B. T he 
I R B’s writte n u nc o n diti o nal a p pr o val of t he st u d y pr ot oc ol a n d t he I C F will be i n t he p ossessi o n 
of t he I n vesti gat or bef ore t he st u d y is i nitiate d. T he I R B’s a p pr o val of t he i n vesti g ati o nal site 
m ust be a vail a ble t o Alla k os pri or t o s hi p me nt of st u d y s u p plies t o t he site. T his a p pr o val m ust 
refer t o t he st u d y b y e xact pr ot o c ol title a n d n u m ber a n d s h o ul d i d e ntif y t he d oc u me nts re vie we d 
a n d t he date of re vie w.  
T he I R B m ust be i nf or me d of re visi o ns t o ot her d oc u me nts ori gi nall y s u b mitte d f or re vi e w; 
seri o us a n d/ or u ne x pecte d a d v erse e x perie nces occ urri n g d uri n g t h e st u d y i n acc or da nce wit h t he 
sta n dar d o perati n g pr oce d ures a n d p olicies of t he I R B; ne w i nf or mati o n t h at ma y a d v ersel y 
affect t he safet y of t he p atie nts or t he c o n d uct of t he st u d y; a n a n n ual u p date a n d/ or re q uest f or 
rea p pr o val; a n d w he n t he st u d y has bee n c o m plete d. 
1 7. 3  
I nf or me d C o nse nt F or m 
Pri or t o st u d y e nr oll m e nt, all p atie nts m ust c o nse nt t o partici pate. T h e pr ocess of o btai ni n g t h e 
i nf or me d c o nse nt will c o m pl y wit h all fe deral re g ulati o ns, I C H r e q uire me nts, a n d l ocal la ws. 
T he I n vesti gat or or desi g nee will r e vie w t h e st u d y a n d t he I C F wit h eac h p ote ntial pati e nt. T he 
re vie w will i ncl u de t he nat ure, sc o pe, pr oce d ures, a n d p ossi ble c o nse q ue nces of partici pati o n i n 
t he st u d y. T he c o nse nt a n d re vie w m ust be i n a f or m u n dersta n da ble t o t he p ote ntial patie nt. T he 
I n vesti gat or or desi g nee a n d t he patie nt m ust b ot h si g n a n d date t he I C F after re vi e w a n d bef ore 
t he patie nt ca n partici pate i n t h e st u d y. T he patie nt will recei ve a c o p y of t he si g ne d a n d date d 
f or m, a n d t he ori gi n al will be retai ne d i n t h e sit e’s st u d y files. T he I n vesti gat or or desi g nee m ust 
e m p hasize t o t he p atie nt t h at st u d y partici pati o n is e ntirel y v ol u ntar y a n d t hat c o nse nt r e gar di n g 
st u d y partici pati o n ma y be wit h dra w n at a n y ti me wit h o ut pe nalt y or l oss of be nefits t o w hic h t he 
patie nt is ot h er wise e ntitle d.  
I n a d diti o n, pri or t o u n der g oi n g bi o psi es, patie nts will pr o vi de i nf or m e d c o nse nt i n acc or da nce 
wit h t h e sta n dar d o perati n g pr oce d ures a n d p olicies of t he E G D facilit y/i n vesti gati o nal sit e.  
1 7. 4  
P u blic ati o ns 
T he pre parati o n a n d s u b mittal f or p u blicati o n of ma n uscri pts c o ntai ni n g t he st u d y res ults s hall be 
i n acc or da nce wit h a pr ocess deter mi ne d b y m ut u al writte n a gree me nt a m o n g t he st u d y S p o ns or 
a n d res p ecti v e sit e. T h e p u blicati o n or prese ntati o n of a n y st u d y res ults s hall c o m pl y wit h all 
a p plica ble pri vac y la ws i ncl u di n g b ut n ot li mite d t o t he HI P A A of 1 9 9 6.  


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 7 of 9 9 
 
1 7. 5  
Cli ni c al Tri al Re gistr ati o n 
T his cli nical trial is re gistere d as N C T 0 4 6 2 0 8 1 1 o n t h e Cli nical Trial Re gistr y We bsite, 
w w w. Cli nical Trials. g o v. 
1 7. 6  
P a y me nt t o P atie nts 
All patie nts ma y be c o m pe nsate d f or partici p ati n g i n t his st u d y i n acc or da nce wit h t h e pa y me nt 
a m o u nts per st u d y da y state d i n t he patie nt’s si g ne d I C F a p pr o ve d b y t he I R B. If t he patie nt is 
disc o nti n ue d fr o m t h e st u d y pri or t o t he last st u d y visit, t h e patie nt will b e c o m pe nsate d f or eac h 
c o m plete d st u d y visit o n a pr o rata basis, as st ate d i n t he patie nt’s I C F.  
After e nr oll m e nt, patie nts at partici pati n g st u d y sites will be c o m pe nsate d f or eac h c o m plete d 
wee k of dail y q uesti o n naires as l o n g as at least 4 q uesti o n naires per wee k are c o m plete d. Patie nts 
ma y be rei m b urse d f or e x pe nses ass o ciate d wit h atte n di n g st u d y visits. N o c o m pe nsati o n be y o n d 
w hat is state d i n t he I C F is per mitte d.  
1 7. 7  
I n v esti g at or Res p o nsi bilities  
B y si g ni n g t he A gree me nt of I n vesti gat or f or m, t he I n vesti gat or a grees t o: 
1)
C o n d uct t h e st u d y i n acc or da nce wit h t he pr ot o c ol a n d o nl y ma ke c ha n ges after n otif yi n g
t he S p o ns or ( or desi g nee), e xce pt w he n t o pr otect t he safet y, ri g hts, or welfare of patie nts.
2)
Pers o nall y c o n d uct or s u per vise t he st u d y.
3)
E ns ure t h at t h e re q uir e me nts relati n g t o o btai ni n g i nf or me d c o nse nt a n d I R B re vie w a n d
a p pr o val m eet fe deral g ui deli nes.
4)
Re p ort t o t he S p o ns or or desi g nee a n y A E t hat occ ur i n t he c o urse of t he st u d y i n
acc or da nce wit h 2 1 C F R Part 3 1 2. 6 4 a n d I C H G ui deli n e E 2 A.
5)
E ns ure t h at all ass ociates, c ollea g ues, a n d e m pl o yees assisti n g i n t he c o n d uct of t h e st u d y
are i nf or me d a b o ut t heir o bli gati o ns i n meeti n g t he a b o ve c o m mit m e nts.
6)
Mai ntai n a de q uate a n d acc urate rec or ds i n acc or da nce wit h 2 1 C F R Part 3 1 2. 6 2 a n d I C H
G ui deli ne E 6 a n d t o ma ke t h ose rec or ds a vaila ble f or i ns pecti o n wit h t he S p o ns or ( or
desi g nee).
7)
E ns ure t h at a n I R B t h at c o m plies wit h t h e re q uire me nts of 2 1 C F R Part 5 6 a n d I C H
G ui deli ne E 6 will be res p o nsi ble f or i niti al a n d c o nti n ui n g r e vie w a n d a p pr o val of t he
cli nical st u d y.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 8 of 9 9 
 
8)
Pr o m ptl y re p ort t o t he I R B a n d t he S p o ns or ( or desi g nee) all c ha n ges i n t h e researc h
acti vit y a n d all u na nti ci pate d pr o ble ms i n v ol vi n g ris ks t o patie nts or ot h ers (t o i n cl u de
a me n d me nts a n d I N D safet y re p orts).
9)
See k I R B a p pr o val bef ore a n y c ha n ges are ma de i n t h e researc h st u d y e xce pt w he n
necess ar y t o eli mi n ate hazar ds t o t he patie nts.
1 0)
C o m pl y wit h all ot her re q uire me nts re gar di n g t he o bli g ati o ns of cli nical I n vesti g at ors a n d
all ot her perti ne nt re q uire me nts liste d i n 2 1 C F R Part 3 1 2.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 7 9 of 9 9 
 
1 8.
Refere nces
Al h m o u d T, H a ns o n J A, Paras her G. E osi n o p hili c gastr oe nteritis: a n u n der dia g n ose d c o n diti o n. 
Di g Dis Sci, 2 0 1 6; 6 1( 9): 2 5 8 5 – 9 2. 
Be dell A, T aft T, Cra ve n M, G ua da g n oli L, Hira n o I, G o nsal ves N. I m pact o n healt h-relate d 
q ualit y of life i n a d ults wit h e osi n o p hilic gastritis a n d gastr oe nteritis: A q ualitati ve 
assess me nt. Di g Dis Sci, 2 0 1 8; 6 3: 1 1 4 8 – 5 7. 
B oc h ner B. Si glec- 8 o n h u m a n e osi n o p hils a n d mast cells, a n d Si glec- F o n m uri ne e osi n o p hils, 
are f u ncti o nall y relate d i n hi bit or y rece pt ors. Cli n E x p Aller g y, 2 0 0 9; 3 9( 3): 3 1 7- 2 4. 
Cal d well J, C olli ns M, St uc ke E, et al. Hist ol o gic e osi n o p hilic gastritis is a s yste mic dis or der 
ass ociate d wit h bl o o d a n d e xtra gastric e osi n o p hilia, T H 2 i m m u nit y, a n d a u ni q ue gastric 
tra nscri pt o me. J Aller g y Cli n I m m u n ol, 2 0 1 4; 1 3 4( 5): 1 1 1 4- 2 4. 
Dell o n E, Peters o n K, M urra y J, Fal k G, G o nsal ves N, C he ha de M, et al. A nti- Si glec- 8 a nti b o d y 
f or e osi n o p hili c gastritis a n d d u o de nitis. N E n gl J Me d, 2 0 2 0; 3 8 3: 1 6 2 4 – 3 4. 
F o o d a n d Dr u g A d mi nistrati o n. Birt h C o ntr ol C hart fr o m F D A. g o v/c o ns u mers/free- p u bli cati o ns-
w o me n/ birt h-c o ntr ol. F D A. g o v/c o ns u mers/free- p u blicati o ns- w o me n/ birt h-c o ntr ol, 
2 1 J u n 2 0 2 1, retrie ve d 2 7 F e b 2 0 2 2, fr o m htt ps:// w w w.f da. g o v/c o ns u mers/fr ee-
p u blicati o ns- w o me n/ birt h-c o ntr ol. 
Je nse n E, Marti n C, Ka p pel ma n M, Dell o n E. Pr e vale nce of e osi n o p hilic gastritis, gastr oe nteritis, 
a n d c olitis: esti mates fr o m a nati o nal a d mi nistr ati ve data base. J Pe diatr Gastr oe nter ol 
N utr, 2 0 1 6; 6 2( 1): 3 6- 4 2. 
Katz P, Gers o n L, Vela M F. G ui deli nes f or t h e dia g n osis a n d ma na ge me nt of gastr oes o p ha geal 
refl u x disease. A m J G astr oe nter ol, 2 0 1 3; 1 0 8( 3): 3 0 8- 2 8. 
L ó pez- Me di na G, G all o M, Pra d o A, Vic u ña- H o n orat o I, Castill o Díaz d e Le ó n R. E osi n o p hilic 
gastr oe nteritis: case re p ort a n d re vie w i n searc h f or dia g n ostic ke y p oi nts. Case Re p 
Gastr oi ntest Me d, 2 0 1 5; 2 0 1 5: 1 – 5. 
Ma ns o or E, Sale h M, C o o per G. Pre vale nce of e osi n o p hili c gastr oe nteritis a n d c olitis i n a 
p o p ulati o n- base d st u d y, fr o m 2 0 1 2- 2 0 1 7. Cli n Gastr oe nter ol He pat ol, 
2 0 1 7; 1 5( 1 1): 1 7 3 3- 1 7 4 1. 
Peters o n K, B yr ne K, Vi ns o n L, Yi n g J, B o y nt o n K, Fa n g J, et al. Ele me ntal diet i n d uces 
hist ol o gic res p o nse i n e osi n o p hilic es o p ha gitis. A m J Gastr oe nter ol, 2 0 1 3; 1 0 8: 7 5 9 – 6 6. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 8 0 of 9 9 
 
Pr ussi n C. E osi n o p hilic g astr oe nteritis a n d relate d e osi n o p hilic dis or ders. Gastr oe nter ol Cli n 
N ort h A m, 2 0 1 4; 4 3( 2): 3 1 7- 2 7. 
Ree d C, W o osle y J, Dell o n E. Cli nical c haracteristics, treat m e nt o utc o mes a n d res o urce 
utili zati o n i n c hil dre n a n d a d ults wit h e osi n o p hilic gastr oe nteritis. Di g Li ver Dis, 
2 0 1 5; 4 7( 3): 1 9 7- 2 0 1. 
Sa m ps o n H, M u ñ oz- F url o n g A, Ca m p bell R, et al. Sec o n d s y m p osi u m o n t h e defi niti o n a n d 
ma na ge me nt of a na p h yla xis: s u m m ar y re p ort-- Sec o n d Nati o nal I nstit ute of Aller g y a n d 
I nfecti o us Disease/ F o o d Aller g y a n d A na p h yla xis Net w or k s y m p osi u m. J All er g y Cli n 
I m m u n ol, 2 0 0 6; 1 1 7( 2): 3 9 1- 7. 
Wec hsl er J, Sc h wart z S, A ms d e n K, Ka gal walla A. Eli mi nati o n diets i n t he ma na ge me nt of 
e osi n o p hilic es o p ha gitis. J Ast h ma Aller g y, 2 0 1 4; 7: 8 5 – 9 4. 
Z ha n g M, Li Y. E osi n o p hili c gastr oe nteritis: a state- of-t he-art re vie w. J Gastr oe nter ol He pat ol, 
2 0 1 7; 3 2( 1): 6 4- 7 2. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 8 1 of 9 9 
 
1 9.
A p pe n di ces
1 9. 1 
A p pe n di x 1: 
E G/ E o D P R O Q uesti o n naire  
1 9. 2 
A p pe n di x 2: 
S h ort F or m- 3 6 Healt h a n d Well- Bei n g S ur ve y Q uesti o n naire  
1 9. 3 
A p pe n di x 3: 
C o m m o n T er mi n ol o g y Criteria f or A d verse E v e nts, Versi o n 5. 0  
1 9. 4 
A p pe n di x 4:
e P R O T eac hi n g T o ol
1 9. 5 
A p pe n di x 5:
A d diti o nal Q uesti o ns
1 9. 6 
A p pe n di x 6: 
E G D Hist ol o g y I nstr ucti o ns
1 9. 7 
A p pe n di x 7: 
Sa m ps o n’s Criteria of A na p h yla xis


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 8 2 of 9 9 
1 9. 1
A p pe n di x 1: E G/ E o D P R O Q uesti o n n aire


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 8 3 of 9 9 
1 9. 1 
A p pe n di x 1: E G/ E o D P R O Q uesti o n n aire c o nt.




Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 8 5 of 9 9 
1 9. 2
A p pe n di x 2: S h o rt F or m- 3 6 He alt h a n d W ell- Bei n g S ur ve y Q uesti o n n aire


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 8 6 of 9 9 
1 9. 2 
A p pe n di x 2: S h o rt F or m- 3 6 He alt h a n d W ell- Bei n g S ur ve y c o nt.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 8 7 of 9 9 
1 9. 2 
A p pe n di x 2: S h o rt F or m- 3 6 He alt h a n d W ell- Bei n g S ur ve y c o nt.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 8 8 of 9 9 
1 9. 2 
A p pe n di x 2: S h o rt F or m- 3 6 He alt h a n d W ell- Bei n g S ur ve y c o nt.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 8 9 of 9 9 
1 9. 2 
A p pe n di x 2: S h o rt F or m- 3 6 He alt h a n d W ell- Bei n g S ur ve y c o nt.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 9 0 of 9 9 
1 9. 2 
A p pe n di x 2: S h o rt F or m- 3 6 He alt h a n d W ell- Bei n g S ur ve y c o nt.




Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 2 of 9 9 
 
1 9. 4  
A p pe n di x 4: e P R O Te ac hi n g T o ol


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 3 of 9 9 
 
1 9. 4 
A p pe n di x 4: e P R O Te ac hi n g T o ol c o nt.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 4 of 9 9 
 
1 9. 4 
A p pe n di x 4: e P R O Te ac hi n g T o ol c o nt.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 5 of 9 9 
 
1 9. 4 
A p pe n di x 4: e P R O Te ac hi n g T o ol c o nt.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2
All a k os I nc.
Pa ge 9 6 of 9 9 
1 9. 5
A p pe n di x 5: A d diti o n al Q u esti o ns 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 7 of 9 9 
 
1 9. 6  
A p pe n di x 6: E G D Hist ol o g y Directi o ns
Details f or c ollecti n g, la beli n g, a n d s hi p pi n g s p eci m e ns will be pr o vi de d se paratel y i n t h e 
Ce ntral Hist ol o g y Ma n u al. 
St ai ni n g 
T he perf or ma nce of t he e val u ati o ns liste d bel o w will re q uir e t he f oll o wi n g stai ns f or eac h 
bi o ps y set:
Es o p ha g us: 1) H & E; 2) tr y ptase; 3) tric hr o me
St o mac h: 
1) H . pyl ori i m m u n ostai n; 2) H & E; 3) tr y ptase; 4) tric hr o me
D u o de n u m: 1) H & E; 2) tr y ptase; 3) tric hr o me
Bi o psies will be o bt ai ne d fr o m t he f oll o wi n g:
Es o p h a g us  (o nly if t h e s u bject has a hist or y of c o nc o mita nt E o E, if es o p ha g us l o o ks
s us pici o us f or E o E or if patie nt is s y m pt o matic o n d ys p ha gia q uesti o n)
A set of 2 fra g me nts fr o m t h e dist al es o p ha g us.
A set of 2 fra g me nts fr o m t h e mi d- pr o xi mal es o p ha g us.
U p t o 2 e xtra s peci me ns ma y be c oll ecte d if t here are a n y a d diti o nal areas of i nterest.
St o m ac h
A set of 4 s peci m e ns fr o m se parate areas of t h e gastric a ntr u m ( 2 – 5 c m pr o xi mal t o
t he p yl or us).
A set of 4 s peci m e ns fr o m se parate areas of t h e gastric c or p us ( 2 fr o m t he pr o xi mal
lesser c ur v at ure a n d 2 fr o m t he greater c ur vat ure).
U p t o 2 e xtra s peci me ns ma y be c oll ecte d if t here are a n y a d diti o nal areas of i nterest.
D u o de n u m
4 fra g me nts of d u o de nal m uc osa fr o m t h e sec o n d a n d t hir d part of t h e d u o de n u m.
U p t o 2 e xtra s peci me ns ma y be c oll ecte d if t here are a n y a d diti o nal areas of i nterest.
T he f oll o wi n g will be re p o rte d f or es o p h a ge al bi o psies:  
Ma xi m u m n u m ber of e osi n o p hils per h pf.
Ma xi m u m n u m ber of tr y ptase- p ositi ve mast cells per h pf.


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 8 of 9 9 
 
1 9. 6 
A p pe n di x 6: E G D Hist ol o g y Directi o ns c o nt.  
T he f oll o wi n g hist o pat h ol o gic para meters will be gra de d fr o m 0 (a bse nt) t o 3 ( mar k e d or se vere):
E osi n o p hilic micr oa bscesses
E osi n o p hilic de gra n ulati o n
Basal z o ne h y per plasi a
S p o n gi osis
S u be pit h elial tiss ue prese nt ( Y/ N)
L a mi n a pr o pri a  fi br osis ( gra de o nl y if s u be pit helial tiss ue is prese nt)
T he f oll o wi n g will be re p o rte d f or g astric bi o psies:
C o nfir m ati o n of a bse nce of H . pyl ori. A hi g hl y se nsiti ve m o n ocl o nal i m m u n o hist oc he mical
stai n will be use d. If ne gati ve, t he n t he p atie nt ca n b e i ncl u de d i n t he st u d y, a n d t he
f oll o wi n g hist o pat h ol o gic para meters will be gra de d usi n g t he S y d ne y S yste m fr o m
0 (a bse nt) t o 3 ( mar ke d or se ver e) f or all e xce pt e osi n o p hil c o u nts.
Ma xi m u m n u m ber of e osi n o p hils per h pf
Ma xi m u m n u m ber of tr y ptase- p ositi ve mast cells per h pf
Acti ve i nfla m mati o n
C hr o nic i nfla m mati o n
I ntesti nal meta plasia
Atr o p h y
Reacti ve gastr o pat h y
T he f oll o wi n g will be re p o rte d f or d u o de n al bi o psies:
Ma xi m u m n u m ber of e osi n o p hils per h pf
Ma xi m u m n u m ber of tr y ptase- p ositi ve mast cells per h pf
D u o de nal i ntrae pit helial l y m p h oc yt osis ( wit h c o u nts/ 1 0 0 e nter oc ytes w he n c o u nt is > 2 0)
Vill o us arc hitect ure
N ote:
A n y st ore d tiss u e fr o m bi o psies of t he es o p ha g us, st o mac h, or d u o de n u m ma y b e use d f or 
e x pl orat or y a nal ysis. 


Pr ot oc ol A K 0 0 2- 0 1 6 X 
A m e n d m e nt 2 
Date: 2 3 Mar 2 0 2 2  
All a k os I nc. 
Pa ge 9 9 of 9 9 
 
1 9. 7  
A p pe n di x 7: S a m ps o n’s Crit eri a of A n a p h yl a xis 
A N A P H Y L A XI S : Sa m ps o n’s defi niti o n of a na p h yla xis (cli nical defi niti o n) is t h e ac ute o nset of 
ill n ess ( mi n utes t o se veral h o urs) w hic h i n v ol ves S KI N, M U C O S A L TI S S U E , or B O T H  (e. g., 
ge neralize d hi v es, pr urit us or fl us hi n g, s w olle n li ps-t o n g ue u v ula) wit h 1 O R m ore of t he 
f oll o wi n g (Sa m ps o n, 2 0 0 6 ): 
R E S PI R A T O R Y : Air wa y c o m pr o mise (e. g., d ys p nea, w heeze, or br o nc h os pas m, stri d or,
re d uce d P E F, h y p o xe mia)
CI R C U L A T O R Y : Re d uce d bl o o d press ure or ass ociate d s y m pt o ms of e n d- or ga n
d ysf u ncti o n (e. g., h y p ot o nia, s y nc o pe)
O R
2 or M O R E of t he f oll o wi n g t h at occ ur r a pi dly after e x p os ure:  
S KI N, M U C O S A L TI S S U E:  e. g., ge neralize d hi ves, itc h-fl us h, s w olle n li ps-t o n g ue- u v ula
R E S PI R A T O R Y: Air wa y c o m pr o mise (e. g., d ys p nea, w heeze, or br o nc h os pas m, stri d or
a n d re d u ce d P E F)
CI R C U L A T O R Y: Re d uce d bl o o d press ure or ass ociate d s y m pt o ms of e n d- or ga n
d ysf u ncti o n (e. g., h y p ot o nia, s y nc o pe)
G A S T R OI N T E S TI N A L: Persiste nt gastr oi ntesti n al s y m pt o ms (e. g., Cra m p y a b d o mi nal
pai n, v o miti n g, na usea, diarr hea)